2024-03-28T08:31:35Zhttps://vtechworks.lib.vt.edu/server/oai/requestoai:vtechworks.lib.vt.edu:10919/1119962023-04-28T13:05:17Zcom_10919_5com_10919_25799com_10919_24216com_10919_5539com_10919_24259com_10919_5559com_10919_23765com_10919_24261com_10919_23261com_10919_24263com_10919_91912com_10919_23198col_10919_70873col_10919_24286col_10919_24342col_10919_24353col_10919_24343col_10919_23262col_10919_24345col_10919_91916
Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review
Hendricks-Wenger, Alissa
Arnold, Lauren
Gannon, Jessica
Simon, Alex
Singh, Neha
Sheppard, Hannah
Nagai-Singer, Margaret A.
Imran, Khan Mohammed
Lee, Kiho
Clark-Deener, Sherrie
Byron, Christopher R.
Edwards, Michael R.
Larson, Martha M.
Rossmeisl, John H.
Coutermarsh-Ott, Sheryl
Eden, Kristin
Dervisis, Nikolaos G.
Klahn, Shawna L.
Tuohy, Joanne L.
Allen, Irving C.
Vlaisavljevich, Eli
Medical imaging
medical transducers
system and device design
therapeutics
CAVITATIONAL ULTRASOUND THERAPY
HEPATOCELLULAR-CARCINOMA
COMPARATIVE BIOLOGY
TISSUE STIFFNESS
VX-2 TUMOR
LIVER
DOGS
OSTEOSARCOMA
FREQUENCY
PIGS
Cancer
New therapeutic strategies are direly needed in the fight against cancer. Over the last decade, several tumor ablation strategies have emerged as stand-alone or combination therapies. Histotripsy is the first completely noninvasive, nonthermal, and nonionizing tumor ablation method. Histotripsy can produce consistent and rapid ablations, even near critical structures. Additional benefits include real-time image guidance, high precision, and the ability to treat tumors of any predetermined size and shape. Unfortunately, the lack of clinically and physiologically relevant preclinical cancer models is often a significant limitation with all focal tumor ablation strategies. The majority of studies testing histotripsy for cancer treatment have focused on small animal models, which have been critical in moving this field forward and will continue to be essential for providing mechanistic insight. While these small animal models have notable translational value, there are significant limitations in terms of scale and anatomical relevance. To address these limitations, a diverse range of large animal models and spontaneous tumor studies in veterinary patients have emerged to complement existing rodent models. These models and veterinary patients are excellent at providing realistic avenues for developing and testing histotripsy devices and techniques designed for future use in human patients. Here, we provide a review of animal models used in preclinical histotripsy studies and compare histotripsy ablation in these models using a series of original case reports across a broad spectrum of preclinical animal models and spontaneous tumors in veterinary patients.
2022-09-26T12:15:24Z
2022-09-26T12:15:24Z
2022-09-26T12:15:24Z
2021-09-03
Article - Refereed
0885-3010
http://hdl.handle.net/10919/111996
https://doi.org/10.1109/TUFFC.2021.3110083
69
1
Vlaisavljevich, Eli [0000-0002-4097-6257]
Larson, Martha [0000-0003-4229-5866]
Clark-Deener, Sherrie [0000-0002-6620-0625]
Allen, Irving [0000-0001-9573-5250]
Dervisis, Nikolaos [0000-0003-2869-1483]
Eden, Kristin [0000-0001-5309-5830]
34478363
1525-8955
en
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000736741000005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
IEEE
oai:vtechworks.lib.vt.edu:10919/1140182023-06-20T19:09:10Zcom_10919_5com_10919_25799com_10919_24216com_10919_5539com_10919_24259com_10919_5559com_10919_24263col_10919_70873col_10919_24286col_10919_24342col_10919_24345
Mechanical High-Intensity Focused Ultrasound (Histotripsy) in Dogs with Spontaneously Occurring Soft Tissue Sarcomas
Ruger, Lauren N.
Yang, Ester
Gannon, Jessica
Sheppard, Hannah
Coutermarsh-Ott, Sheryl
Ziemlewicz, Timothy J.
Dervisis, Nikolaos G.
Allen, Irving C.
Daniel, Gregory B.
Tuohy, Joanne L.
Vlaisavljevich, Eli
Klahn, Shawna L.
Biomedical Imaging
Cancer
Introduction: Histotripsy is a non-invasive focused ultrasound therapy that uses controlled acoustic cavitation to mechanically disintegrate tissue. To date, there are no reports investigating histotripsy for the treatment of soft tissue sarcoma (STS). Objective: This study aimed to investigate the in vivo feasibility of ablating STS with histotripsy and to characterize the impact of partial histotripsy ablation on the acute immunologic response in canine patients with spontaneous STS. Methods: A custom 500 kHz histotripsy system was used to treat ten dogs with naturally occurring STS. Four to six days after histotripsy, tumors were surgically resected. Safety was determined by monitoring vital signs during treatment and post-treatment physical examinations, routine lab work, and owners’ reports. Ablation was characterized using radiologic and histopathologic analyses. Systemic immunological impact was evaluated by measuring changes in cytokine concentrations, and tumor microenvironment changes were evaluated by characterizing changes in infiltration with tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) using multiplex immunohistochemistry and differential gene expression. Results: Results showed histotripsy ablation was achievable and well-tolerated in all ten dogs. Immunological results showed histotripsy induced pro-inflammatory changes in the tumor microenvironment. Conclusion & Significance: Overall, this study demonstrates histotripsy's potential as a precise, non-invasive treatment for STS.
2023-03-01T17:34:56Z
2023-03-01T17:34:56Z
2023-03-01T17:34:56Z
2023-03
Article - Refereed
0018-9294
http://hdl.handle.net/10919/114018
https://doi.org/10.1109/TBME.2022.3201709
70
3
Vlaisavljevich, Eli [0000-0002-4097-6257]
Allen, Irving [0000-0001-9573-5250]
Dervisis, Nikolaos [0000-0003-2869-1483]
Tuohy, Joanne [0000-0003-1516-3841]
36006886
1558-2531
en
https://www.ncbi.nlm.nih.gov/pubmed/36006886
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
IEEE
oai:vtechworks.lib.vt.edu:10919/1072922022-02-26T00:17:12Zcom_10919_5com_10919_25799com_10919_78629com_10919_78628com_10919_24259com_10919_5559col_10919_70873col_10919_78630col_10919_24342
Human norovirus animal model essential for vaccine development
Yuan, Lijuan
Parreño, Viviana
Ramesh, Ashwin
Human noroviruses are the most common cause of acute gastroenteritis and represent an incredibly high burden on the healthcare sector. Currently no vaccines or drugs exist to prevent or treat the disease. This is in part due to a lack of animal models. Here, Dr Lijuan Yuan and the team at Virginia Polytechnic Institute and State University developed and validated gnotobiotic pigs as an animal model for the human norovirus GII.4/2003 Cin-2. Determining dose-response relationships as well as the median infectious dose, by using different statistical approaches for this virus, means we are one step closer on the path to vaccine development.
2021-12-30T17:28:38Z
2021-12-30T17:28:38Z
2021-12-30T17:28:38Z
2021-12-29
Article
http://hdl.handle.net/10919/107292
Yuan, Lijuan [0000-0003-0709-5228]
en
http://researchfeatures.com/
https://researchfeatures.com/human-norovirus-animal-model-essential-vaccine-development/
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
Research Features
oai:vtechworks.lib.vt.edu:10919/1140252023-03-03T16:00:13Zcom_10919_5com_10919_25799com_10919_24216com_10919_5539com_10919_24259com_10919_5559com_10919_23765com_10919_23261com_10919_24263com_10919_91912com_10919_23198col_10919_70873col_10919_24286col_10919_24342col_10919_24353col_10919_23262col_10919_24345col_10919_91916
Histotripsy Ablation of Bone Tumors: Feasibility Study in Excised Canine Osteosarcoma Tumors
Arnold, Lauren
Hendricks-Wenger, Alissa
Coutermarsh-Ott, Sheryl
Gannon, Jessica
Hay, Alayna N.
Dervisis, Nikolaos G.
Klahn, Shawna L.
Allen, Irving C.
Tuohy, Joanne L.
Vlaisavljevich, Eli
Histotripsy
Focused ultrasound
Osteosarcoma
Bone
Tumors
Ablation
Osteosarcoma (OS) is a primary bone tumor affecting both dogs and humans. Histotripsy is a non-thermal, non-invasive focused ultrasound method using controlled acoustic cavitation to mechanically disintegrate tissue. In this study, we investigated the feasibility of treating primary OS tumors with histotripsy using a 500-kHz transducer on excised canine OS samples harvested after surgery at the Veterinary Teaching Hospital at Virginia Tech. Samples were embedded in gelatin tissue phantoms and treated with the 500-kHz histotripsy system using one- or two-cycle pulses at a pulse repetition frequency of 250 Hz and a dosage of 4000 pulses/point. Separate experiments also assessed histotripsy effects on normal canine bone and nerve using the same pulsing parameters. After treatment, histopathological evaluation of the samples was completed. To determine the feasibility of treating OS through intact skin/soft tissue, additional histotripsy experiments assessed OS with overlying tissues. Generation of bubble clouds was achieved at the focus in all tumor samples at peak negative pressures of 26.2 ± 4.5 MPa. Histopathology revealed effective cell ablation in treated areas for OS tumors, with no evidence of cell death or tissue damage in normal tissues. Treatment through tissue/skin resulted in generation of well-confined bubble clouds and ablation zones inside OS tumors. Results illustrate the feasibility of treating OS tumors with histotripsy.
CORRIGENDUM: The authors regret that errors were present in the above article. The legend for Figure 5 on page 3441 should read “Fig. 5. Normal, healthy, non-neoplastic bone was excised from amputated canine limbs and subjected to histology. No histological differences were noted between untreated (a: magnification 4 x, b: magnification 40 x) and treated samples (c: magnification 4 x, d: magnification 40 x).” Also, the final section heading on page 3439 should read “Histotripsy ablation of ex vivo bone and nerve specimens.” Finally, the reference after the last complete sentence on page 3437 is incomplete and should read “Focal pressure waveforms for the 500-kHz transducer were measured using a custom-built fiberoptic hydrophone (FOPH) in degassed water at the focal point of each transducer (Parsons et al. 2006).” The authors would like to apologise for any inconvenience caused.
2023-03-02T18:58:13Z
2023-03-02T18:58:13Z
2023-03-02T18:58:13Z
2021-12
Article - Refereed
0301-5629
S0301-5629(22)00119-3 (PII)
http://hdl.handle.net/10919/114025
https://doi.org/10.1016/j.ultrasmedbio.2021.08.004
47
12
Tuohy, Joanne [0000-0003-1516-3841]
Allen, Irving [0000-0001-9573-5250]
Dervisis, Nikolaos [0000-0003-2869-1483]
Vlaisavljevich, Eli [0000-0002-4097-6257]
35400542
1879-291X
en
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000810240600017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
Elsevier
oai:vtechworks.lib.vt.edu:10919/490852023-12-19T13:34:26Zcom_10919_24259com_10919_5559com_10919_24263col_10919_24342col_10919_24345
Serological response of cats to experimental besnoitia darlingi and besnoitia neotomofelis infections and prevalence of antibodies to these parasites in cats from Virginia and Pennsylvania
Houk, Alice E.
Rosypal, A. C.
Grant, David C.
Dubey, Jitender P.
Zajac, Anne M.
Yabsley, Michael J.
Lindsay, David S.
opossum didelphis-marsupialis
sarcocystis-neurona
toxoplasma-gondii
neospora-caninum
transmission
parasitology
Besnoitia darlingi and Besnoitia neotomofelis are cyst-forming tissue apicomplexan parasites that use domestic cats (Felis domesticus) as definitive hosts and opossums (Didelphis virginiana) and Southern Plains woodrats (Neotoma micropus) as intermediate hosts, respectively. Nothing is known about the prevalence of B. darlingi or B. neotomofelis in cats from the United States. Besnoitia darlingi infections have been reported in naturally infected opossums from many states in the United States, and B. neotomofelis infections have been reported from Southern Plains woodrats from Texas, but naturally infected cats have not been identified. The present study examined the IgG antibody response of cats to experimental infection (B. darlingi n = 1 cat; B. neotomofelis n = 3 cats). Samples from these cats were used to develop an indirect immunofluorescent antibody test (IFAT), which was then used to examine seroprevalence of IgG antibodies to tachyzoites of B. darlingi and B. neotomofelis in a population of domestic cats from Virginia (N = 232 cats) and Pennsylvania (N = 209). The serum from cats inoculated with B. darlingi or B. neotomofelis cross-reacted with each other's tachyzoites. The titers to heterologous tachyzoites were 1 to 3 dilutions lower than to homologous tachyzoites. Sera from B. darlingi- or B. neotomofelis-infected cats did not react with tachyzoites of Toxoplasma gondii or Neospora caninum or merozoites of Sarcocystis neurona using the IFAT. Antibodies to B. darlingi were found in 14% and 2% of cats from Virginia and Pennsylvania, respectively. Antibodies to B. neotomofelis were found in 5% and 4% of cats from Virginia and Pennsylvania, respectively. Nine cats from Virginia and 1 cat from Pennsylvania were positive for both.
2014-06-20T14:13:22Z
2014-06-20T14:13:22Z
2014-06-20T14:13:22Z
2011-04
Article - Refereed
Alice E. Houk, Alexa C. Rosypal, David C. Grant, J. P. Dubey, Anne M. Zajac, Michael J. Yabsley, and David S. Lindsay (2011). "Serological Response of Cats to Experimental Besnoitia darlingi and Besnoitia neotomofelis Infections and Prevalence of Antibodies to These Parasites in Cats from Virginia and Pennsylvania," Journal of Parasitology, Vol. 97, No. 2, pp. 259-261. doi: http://dx.doi.org/10.1645/GE-2626.1
0022-3395
http://hdl.handle.net/10919/49085
http://www.bioone.org/doi/abs/10.1645/GE-2626.1
https://doi.org/10.1645/ge-2626.1
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
Virginia
Pennsylvania
United States
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/789332021-06-21T19:23:08Zcom_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_78797col_10919_24342col_10919_23146
Chemokines and Chemokine Receptors in the Development of Lupus Nephritis
Liao, Xiaofeng
Pirapakaran, Tharshikha
Luo, Xin M.
Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN.
2017-09-18T09:35:37Z
2017-09-18T09:35:37Z
2017-09-18T09:35:37Z
2016-06-14
Article - Refereed
Xiaofeng Liao, Tharshikha Pirapakaran, and Xin M. Luo, “Chemokines and Chemokine Receptors in the Development of Lupus Nephritis,” Mediators of Inflammation, vol. 2016, Article ID 6012715, 15 pages, 2016. doi:10.1155/2016/6012715
http://hdl.handle.net/10919/78933
https://doi.org/10.1155/2016/6012715
en
http://creativecommons.org/licenses/by/4.0/
Copyright © 2016 Xiaofeng Liao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution 4.0 International
Hindawi
oai:vtechworks.lib.vt.edu:10919/1065472022-02-26T00:17:13Zcom_10919_24259com_10919_5559col_10919_24342
Determining the role of natural SARS-CoV-2 infection in the death of domestic pets: 10 cases (2020-2021)
Carpenter, Ann
Ghai, Ria R.
Gary, Joy
Ritter, Jana M.
Carvallo, Francisco R.
Diel, Diego G.
Martins, Mathias
Murphy, Julia
Schroeder, Betsy A.
Brightbill, Kevin
Tewari, Deepanker
Boger, Lore
Gabel, Julie
Cobb, Robert
Hennebelle, Janemarie
Stanton, James B.
McCullough, Kathryn
Mosley, Yung-Yi C.
Naikare, Hemant K.
Radcliffe, Rachel
Parr, Boyd
Balsamo, Gary
Robbins, Brent
Smith, David
Slavinski, Sally
Williams, Carl
Meckes, Doug
Jones, Dee
Frazier, Tony
Steury, Kelley
Rooney, Jane
Torchetti, Mia
Wendling, Natalie
Currie, Dustin
Behravesh, Casey Barton
Wallace, Ryan M.
OBJECTIVE To establish a pathoepidemiological model to evaluate the role of SARS-CoV-2 infection in the first 10 companion animals that died while infected with SARS-CoV-2 in the US. ANIMALS 10 cats and dogs that tested positive for SARS-CoV-2 and died or were euthanized in the US between March 2020 and January 2021. PROCEDURES A standardized algorithm was developed to direct case investigations, determine the necessity of certain diagnostic procedures, and evaluate the role, if any, that SARS-CoV-2 infection played in the animals' course of disease and death. Using clinical and diagnostic information collected by state animal health officials, state public health veterinarians, and other state and local partners, this algorithm was applied to each animal case. RESULTS SARS-CoV-2 was an incidental finding in 8 animals, was suspected to have contributed to the severity of clinical signs leading to euthanasia in 1 dog, and was the primary reason for death for 1 cat. CONCLUSIONS AND CLINICAL RELEVANCE This report provides the global community with a standardized process for directing case investigations, determining the necessity of certain diagnostic procedures, and determining the clinical significance of SARS-CoV-2 infections in animals with fatal outcomes and provides evidence that SARS-CoV-2 can, in rare circumstances, cause or contribute to death in pets.
2021-11-08T19:34:57Z
2021-11-08T19:34:57Z
2021-11-08T19:34:57Z
2021-11-01
Article - Refereed
0003-1488
http://hdl.handle.net/10919/106547
https://doi.org/10.2460/javma.259.9.1032
259
9
34647475
1943-569X
en
http://creativecommons.org/publicdomain/mark/1.0/
Public Domain (U.S.)
oai:vtechworks.lib.vt.edu:10919/1145612023-12-19T13:34:26Zcom_10919_5540com_10919_24259com_10919_5559com_10919_91912com_10919_23198col_10919_71752col_10919_24342col_10919_91916
Phenotypic Drift in Lupus-Prone MRL/lpr Mice: Potential Roles of MicroRNAs and Gut Microbiota
Cabana-Puig, Xavier
Bond, Jacob M.
Wang, Zhuang
Dai, Rujuan
Lu, Ran
Lin, Amy
Oakes, Vanessa
Rizzo, Amy
Swartout, Brianna
Abdelhamid, Leila
Mao, Jiangdi
Prakash, Meeta
Sangmeister, Constanza
Cheung, Nathaniel
Cowan, Catharine
Reilly, Christopher M.
Sun, Sha
Ahmed, S. Ansar
Luo, Xin M.
MRL/lpr mice have been extensively used as a murine model of lupus. Disease progression in MRL/lpr mice can differ among animal facilities, suggesting a role for environmental factors.We noted a phenotypic drift of our in-house colony, which was the progeny of mice obtained from The Jackson Laboratory (JAX; stocking number 000485), that involved attenuated glomerulonephritis, increased splenomegaly, and reduced lymphadenopathy. To validate our in-house mice as a model of lupus, we compared these mice with those newly obtained from JAX, which were confirmed to be genetically identical to our in-house mice. Surprisingly, the new JAX mice exhibited a similar phenotypic drift, most notably the attenuation of glomerulonephritis. Interestingly, our in-house colony differed from JAX mice in body weight and kidney size (both sexes), as well as in splenic size, germinal center formation, and level of anti-dsDNA auto-IgG in the circulation (male only). In addition, we noted differential expression of microRNA (miR)-21 and miR-183 that might explain the splenic differences in males. Furthermore, the composition of gut microbiota was different between in-house and new JAX mice at early time points, which might explain some of the renal differences (e.g., kidney size). However, we could not identify the reason for attenuated glomerulonephritis, a shared phenotypic drift between the two colonies. It is likely that this was due to certain changes of environmental factors present in both JAX and our facilities. Taken together, these results suggest a significant phenotypic drift in MRL/lpr mice in both colonies that may require strain recovery from cryopreservation.
2023-04-18T17:54:53Z
2023-04-18T17:54:53Z
2023-04-18T17:54:53Z
2022
Article - Refereed
http://hdl.handle.net/10919/114561
https://doi.org/10.4049/immunohorizons.2100082
6
1
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
American Association of Immunologists
oai:vtechworks.lib.vt.edu:10919/1029052022-02-26T00:17:13Zcom_10919_24259com_10919_5559col_10919_24342
Neosporosis, Toxoplasmosis, and Sarcocystosis in Ruminants: An Update
Lindsay, David S.
Dubey, Jitender P.
Biomedical Sciences and Pathobiology
Neospora caninum
T gondii
Sarcocystis spp.
Cattle
Sheep
Goats
Water buffalo
White-tailed deer
Neospora caninum, Toxoplasma gondii, and Sarcocystis spp. are related Apicomplexan parasites that have 2 hosts in their life cycles. The definitive hosts excrete unsporulated (Neospora caninum, T gondii) or sporulated (Sarcocystis spp.) oocysts in their feces after ingesting tissue cysts from the tissues of ruminant intermediate hosts. These coccidians can cause abortion and neonatal mortality in ruminants. T gondii and Sarcocystis hominis (from cattle) are zoonotic. This article reviews information on the etiology, life cycle, diagnosis, control and prevention of these parasites and the diseases they cause in ruminants.
2021-03-31T12:23:44Z
2021-03-31T12:23:44Z
2021-03-31T12:23:44Z
2020-03
Article - Refereed
0749-0720
http://hdl.handle.net/10919/102905
https://doi.org/10.1016/j.cvfa.2019.11.004
36
1
32029185
1558-4240
en
http://creativecommons.org/publicdomain/mark/1.0/
Public Domain
oai:vtechworks.lib.vt.edu:10919/490612023-12-19T13:34:26Zcom_10919_24259com_10919_5559col_10919_24342
Non-sand fly transmission of a North American isolate of Leishmania infantum in experimentally infected BALB/c mice
Rosypal, A. C.
Lindsay, David S.
congenital kala-azar
visceral leishmaniasis
kinetoplast dna
newborn
puppy
blood
diagnosis
serology
dogs
pcr
parasitology
Leishmania infantum, an etiologic agent of zoonotic visceral leishmaniasis, is endemic in the foxhound population in the United States and Canada. Leishmaniasis is usually transmitted by blood-feeding sand flies; however, epidemiological data do not support a significant role for sand flies in the maintenance of foxhound infections in North America, and an alternate mode of transmission may exist. The present study was conducted to determine if transplacental or direct transmission occurs in pregnant BALB/c mice experimentally infected with L. infantum isolated from a naturally infected foxhound from Virginia as well as to determine if the parasite was directly transmitted to the mates used to breed the mice. Female BALB/c mice were intravenously inoculated with 1 x 10(6) promastigotes of the LIVT-1 strain of L. infantum. Mice were bred to uninfected male BALB/c mice 2 mo postinoculation. Pregnant mice were killed between days 13 and 18 of gestation. Pups and placentas were collected at necropsy, divided, and used for parasite culture and polymerase chain reaction (PCR) analyses. Culture and PCR analyses were performed on spleens from the male mice to determine the possibility of sexual transmission. Leishmania sp. DNA was detected in 4 of 88 pups and 3 of 16 placentas from LIVT-1-inoculated mice. One male mouse used to breed infected females was PCR positive. This work provides evidence for a low level of nonvector transmission of North American L. infantum in a mouse model.
2014-06-20T14:13:17Z
2014-06-20T14:13:17Z
2014-06-20T14:13:17Z
2005-10
Article - Refereed
Alexa C. Rosypal and David S. Lindsay (2005). "Non-sand fly transmission of a North American isolate of Leishmania infantum in experimentally infected BALB/c mice," Journal of Parasitology, Vol. 91, No. 5, pp. 1113-1115. doi: http://dx.doi.org/10.1645/GE-586R.1
0022-3395
http://hdl.handle.net/10919/49061
http://www.bioone.org/doi/abs/10.1645/GE-586R.1
https://doi.org/10.1645/ge-586r.1
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/954952022-02-26T00:17:13Zcom_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_78882col_10919_24342
Tracing Worldwide Turkey Genetic Diversity Using D-loop Sequence Mitochondrial DNA Analysis
Canales Vergara, Amado Manuel
Landi, Vincenzo
Delgado Bermejo, Juan Vicente
Martínez, Amparo
Cervantes Acosta, Patricia
Pons Barro, Águeda
Bigi, Daniele
Sponenberg, D. Phillip
Helal, Mostafa
Hossein Banabazi, Mohammad
Camacho Vallejo, María Esperanza
Meleagris gallopavo
mtDNA
phylogenetic relationships
genetic diversity
populations
According to recent archeological evidence, turkey <i>(Meleagris gallopavo gallopavo)</i> domestication may have occurred in Mexico around 2000 years ago. However, little is known about the phylogenetic and genealogical background underlying domestic turkey populations. This study aimed to further understand the domestication process and identify inter- or intraspecific connections between turkey populations to determine their origins, trace their global expansion, and define the species’ genetic value. Ninety-three domestic turkeys (local breeds) were sampled from populations in Brazil, Mexico, USA, Spain, Italy, Iran, and Egypt. Publicly available sequences from previous studies were also included. Standard mitochondrial DNA, genetic diversity, and haplotype network analyses were performed. Seventy-six polymorphic sites were identified. Turkeys from Mexico showed the greatest number of polymorphic sites (40), while turkeys from Italy and Brazil reported only one site each. Nucleotide diversity was also highest in Mexico and the USA (π = 0.0175 and 0.0102, respectively) and lowest in Brazil and Italy. Of the six major haplogroups defined, the Mexican and USA populations appeared to have remained more stable and diverse than the other populations. This may be due to conservative husbandry policies in the rural areas of other populations, which have prevented the introduction of commercial turkey lines.
2019-11-12T13:32:37Z
2019-11-12T13:32:37Z
2019-11-12T13:32:37Z
2019-11-01
Article - Refereed
Canales Vergara, A.M.; Landi, V.; Delgado Bermejo, J.V.; Martínez, A.; Cervantes Acosta, P.; Pons Barro, Á.; Bigi, D.; Sponenberg, P.; Helal, M.; Hossein Banabazi, M.; Camacho Vallejo, M.E. Tracing Worldwide Turkey Genetic Diversity Using D-loop Sequence Mitochondrial DNA Analysis. Animals 2019, 9, 897.
http://hdl.handle.net/10919/95495
https://doi.org/10.3390/ani9110897
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/490892023-12-19T13:34:26Zcom_10919_24259com_10919_5559col_10919_24342
Survey of Dogs From Vietnam for Antibodies to Visceralizing Leishmania spp
Rosypal, A. C.
Hailemariam, S.
Wekheye, V.
Huong, L. T. T.
Dubey, Jitender P.
Lindsay, David S.
Tidwell, R. R.
parasitology
Cases of visceral leishmaniasis, one of the most neglected tropical diseases, are increasing globally. Dogs are considered all important reservoir host for visceral leishmaniasis in people. The first cases of human visceral leishmaniasis in Vietnam have recently been reported. Blood samples were collected from 41 dogs in rural Vietnam. Sera were examined for antibodies to visceralizing Leishmania spp. by canine immunochromatographic strip assays based on recombinant K39 antigen. Antibodies to Leishmania spp. were not detected in ally of the dogs tested. Results from this study suggest that rural dogs are not likely to be involved in the emergence of human visceral leishmaniasis in Vietnam.
2014-06-20T14:13:23Z
2014-06-20T14:13:23Z
2014-06-20T14:13:23Z
2009-06
Article - Refereed
Alexa C. Rosypal, Sarem Hailemariam, Vitalis Wekheye, Lam Thi Thu Huong, J. P. Dubey, David S. Lindsay, and Richard R. Tidwell (2009). "Survey of Dogs From Vietnam for Antibodies to Visceralizing Leishmania spp.," Journal of Parasitology, Vol. 95, No. 3, pp. 767-767. doi: http://dx.doi.org/10.1645/GE-1828.1
0022-3395
http://hdl.handle.net/10919/49089
http://www.bioone.org/doi/abs/10.1645/GE-1828.1
https://doi.org/10.1645/ge-1828.1
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/1137762023-03-03T14:28:40Zcom_10919_8195com_10919_25799com_10919_24216com_10919_5539com_10919_24259com_10919_5559com_10919_24263col_10919_78882col_10919_24286col_10919_24342col_10919_24345col_10919_23146
Characterizing the Ablative Effects of Histotripsy for Osteosarcoma: In Vivo Study in Dogs
Ruger, Lauren N.
Hay, Alayna N.
Vickers, Elliana R.
Coutermarsh-Ott, Sheryl
Gannon, Jessica M.
Covell, Hannah S.
Daniel, Gregory B.
Laeseke, Paul F.
Ziemlewicz, Timothy J.
Kierski, Katharine R.
Ciepluch, Brittany J.
Vlaisavljevich, Eli
Tuohy, Joanne L.
Osteosarcoma (OS) is a malignant bone tumor treated by limb amputation or limb salvage surgeries and chemotherapy. Histotripsy is a non-thermal, non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. Recent ex vivo and in vivo pilot studies have demonstrated the ability of histotripsy for ablating OS but were limited in scope. This study expands on these initial findings to more fully characterize the effects of histotripsy for bone tumors, particularly in tumors with different compositions. A prototype 500 kHz histotripsy system was used to treat ten dogs with suspected OS at an intermediate treatment dose of 1000 pulses per location. One day after histotripsy, treated tumors were resected via limb amputation, and radiologic and histopathologic analyses were conducted to determine the effects of histotripsy for each patient. The results of this study demonstrated that histotripsy ablation is safe and feasible in canine patients with spontaneous OS, while offering new insights into the characteristics of the achieved ablation zone. More extensive tissue destruction was observed after histotripsy compared to that in previous reports, and radiographic changes in tumor size and contrast uptake following histotripsy were reported for the first time. Overall, this study significantly expands our understanding of histotripsy bone tumor ablation and informs future studies for this application.
2023-02-10T14:44:04Z
2023-02-10T14:44:04Z
2023-02-10T14:44:04Z
2023-01-25
Article - Refereed
Ruger, L.N.; Hay, A.N.; Vickers, E.R.; Coutermarsh-Ott, S.L.; Gannon, J.M.; Covell, H.S.; Daniel, G.B.; Laeseke, P.F.; Ziemlewicz, T.J.; Kierski, K.R.; Ciepluch, B.J.; Vlaisavljevich, E.; Tuohy, J.L. Characterizing the Ablative Effects of Histotripsy for Osteosarcoma: In Vivo Study in Dogs. Cancers 2023, 15, 741.
http://hdl.handle.net/10919/113776
https://doi.org/10.3390/cancers15030741
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/490282023-12-19T13:34:26Zcom_10919_24259com_10919_5559col_10919_24342
Characterization of temperature-sensitive strains of Neospora caninum in mice
Lindsay, David S.
Lenz, S. D.
Blagburn, B. L.
Brake, D. A.
s48 toxoplasma-gondii
killed vaccine
sheep
challenge
pathogenicity
tachyzoites
infections
immunity
hamsters
mutants
parasitology
Temperature-sensitive (ts) strains of the Neospora caninum tachyzoites were selected by chemical mutagenesis and selection for growth at 32 C. Three ts strains and the parental, N. caninum wild-type strain, NC-1, were examined in the present study for their ability to cause disease in inbred BALB/c mice, outbred ICR mice, and chemically immunosuppressed ICR mice. In BALB/c mice, all 3 strains failed to induce clinical disease, whereas infection with the NC-1 strain caused central nervous system disease and death in some mice. No disease was observed in ICR mice inoculated with the 3 ts strains or the NC-I strain. All immunosuppressed ICR mice inoculated with the NC-1 strain died, whereas no immunosuppressed mice inoculated with the NCts-4 strain and only 1 of 5 mice inoculated with the NCts-8 and NCts-12 strains died. The NCts-4 and NCts-12 strains reverted to a wild-type phenotype when grown at 37 C. Vaccination of BALB/c mice with live, but not frozen NCts-8 strain tachyzoites induced significant (P < 0.05) protection following NC-1 strain challenge.
2014-06-20T14:13:09Z
2014-06-20T14:13:09Z
2014-06-20T14:13:09Z
1999-02
Article - Refereed
David S. Lindsay, Steve D. Lenz, Byron L. Blagburn and David A. Brake (1999). "Characterization of temperature-sensitive strains of Neospora caninum in mice," The Journal of Parasitology, Vol. 85, No. 1, pp. 64-67. DOI: 10.2307/3285701
0022-3395
http://hdl.handle.net/10919/49028
http://www.jstor.org/stable/3285701
https://doi.org/10.2307/3285701
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/894832022-02-26T00:17:13Zcom_10919_24259com_10919_5559col_10919_24342
A Novel Pathogenic Mammalian Orthoreovirus from Diarrheic Pigs and Swine Blood Meal in the United States
Narayanappa, Athmaram Thimmasandra
Sooryanarain, Harini
Deventhiran, Jagadeeswaran
Cao, Dianjun
Venkatachalam, Backiyalakshmi Ammayappan
Kambiranda, Devaiah
LeRoith, Tanya
Heffron, C. Lynn
Lindstrom, Nicole
Hall, Karen
Jobst, Peter
Sexton, Cary
Meng, Xiang-Jin
Elankumaran, Subbiah
Since May 2013, outbreaks of porcine epidemic diarrhea have devastated the U.S. swine industry, causing immense economic losses. Two different swine enteric coronaviruses (porcine epidemic diarrhea virus and Delta coronavirus) have been isolated from the affected swine population. The disease has been reported from at least 32 states of the United States and other countries, including Mexico, Peru, Dominican Republic, Canada, Columbia, Ecuador, and Ukraine, with repeated outbreaks in previously infected herds. Here we report the isolation and characterization of a novel mammalian orthoreovirus 3 (MRV3) from diarrheic feces of piglets from these outbreaks in three states and ring-dried swine blood meal from multiple sources. MRV3 could not be isolated from healthy or pigs that had recovered from epidemic diarrhea from four states. Several MRV3 isolates were obtained from chloroform-extracted pig feces or blood meal in cell cultures or developing chicken embryos. Biological characterization of two representative isolates revealed trypsin resistance and thermostability at 90 degrees C. NextGen sequencing of ultrapurified viruses indicated a strong homology of the S1 segment to mammalian and bat MRV3. Neonatal piglets experimentally infected with these viruses or a chloroform extract of swine blood meal developed severe diarrhea and acute gastroenteritis with 100% mortality within 3 days postinfection. Therefore, the novel porcine MRV3 may contribute to enteric disease along with other swine enteric viruses. The role of MRV3 in the current outbreaks of porcine epidemic diarrhea in the United States remains to be determined, but the pathogenic nature of the virus warrants further investigations on its epidemiology and prevalence. IMPORTANCE Porcine orthoreoviruses causing diarrhea have been reported in China and Korea but not in the United States. We have isolated and characterized two pathogenic reassortant MRV3 isolates from swine fecal samples from porcine epidemic diarrhea outbreaks and ring-dried swine blood meal in the United States. These fecal and blood meal isolates or a chloroform extract of blood meal induced severe diarrhea and mortality in experimentally infected neonatal pigs. Genetic and phylogenetic analyses of two MRV3 isolates revealed that they are identical but differed significantly from nonpathogenic mammalian orthoreoviruses circulating in the United States. The present study provides a platform for immediate development of suitable vaccines and diagnostics to prevent and control porcine orthoreovirus diarrhea.
2019-05-10T14:53:57Z
2019-05-10T14:53:57Z
2019-05-10T14:53:57Z
2015-05
Article - Refereed
2150-7511
e00593-15
http://hdl.handle.net/10919/89483
https://doi.org/10.1128/mBio.00593-15
6
3
en
http://creativecommons.org/licenses/by-nc-sa/3.0/
Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
American Society for Microbiology
oai:vtechworks.lib.vt.edu:10919/1119762022-09-26T13:33:44Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559com_10919_24262col_10919_70873col_10919_24342col_10919_24344
Optimizing Pooled Testing for Estimating the Prevalence of Multiple Diseases
Warasi, Md S.
Hungerford, Laura L.
Lahmers, Kevin K.
Animal testing
Experimental design
Group testing
Screening
Surveillance
3 Good Health and Well Being
Pooled testing can enhance the efficiency of diagnosing individuals with diseases of low prevalence. Often, pooling is implemented using standard groupings (2, 5, 10, etc.). On the other hand, optimization theory can provide specific guidelines in finding the ideal pool size and pooling strategy. This article focuses on optimizing the precision of disease prevalence estimators calculated from multiplex pooled testing data. In the context of a surveillance application of animal diseases, we study the estimation efficiency (i.e., precision) and cost efficiency of the estimators with adjustments for the number of expended tests. This enables us to determine the pooling strategies that offer the highest benefits when jointly estimating the prevalence of multiple diseases, such as theileriosis and anaplasmosis. The outcomes of our work can be used in designing pooled testing protocols, not only in simple pooling scenarios but also in more complex scenarios where individual retesting is performed in order to identify positive cases. A software application using the shiny package in R is provided with this article to facilitate implementation of our methods. Supplementary materials accompanying this paper appear online.
2022-09-23T12:14:54Z
2022-09-23T12:14:54Z
2022-09-23T12:14:54Z
2022-08-12
Article - Refereed
1085-7117
PMC9373899
511 (PII)
http://hdl.handle.net/10919/111976
https://doi.org/10.1007/s13253-022-00511-4
Hungerford, Laura [0000-0002-5680-6746]
Lahmers, Kevin [0000-0002-5290-3426]
35975123
1537-2693
en
https://www.ncbi.nlm.nih.gov/pubmed/35975123
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
Springer
oai:vtechworks.lib.vt.edu:10919/1128882022-12-15T08:13:56Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Standardized <i>In vitro</i> Assays to Visualize and Quantify Interactions between Human Neutrophils and <i>Staphylococcus aureus</i> Biofilms
Rana, Pranav S. J. B.
Gloag, Erin S.
Wozniak, Daniel J.
Emerging infectious diseases
Biodefense
Vaccine related
Prevention
Infectious diseases
5 Development of treatments and therapeutic interventions
5.1 Pharmaceuticals
2.2 Factors relating to the physical environment
2 Aetiology
Infection
Neutrophils are the first line of defense deployed by the immune system during microbial infection. In vivo, neutrophils are recruited to the site of infection where they use processes such as phagocytosis, production of reactive oxygen and nitrogen species (ROS, RNS, respectively), NETosis (neutrophil extracellular trap), and degranulation to kill microbes and resolve the infection. Interactions between neutrophils and planktonic microbes have been extensively studied. There have been emerging interests in studying infections caused by biofilms in recent years. Biofilms exhibit properties, including tolerance to killing by neutrophils, distinct from their planktonic-grown counterparts. With the successful establishment of both in vitro and in vivo biofilm models, interactions between these microbial communities with different immune cells can now be investigated. Here, techniques that use a combination of traditional biofilm models and well-established neutrophil activity assays are tailored specifically to study neutrophil and biofilm interactions. Wide-field fluorescence microscopy is used to monitor the localization of neutrophils in biofilms. These biofilms are grown in static conditions, followed by the addition of neutrophils derived from human peripheral blood. The samples are stained with appropriate dyes prior to visualization under the microscope. Additionally, the production of ROS, which is one of the many neutrophil responses against pathogens, is quantified in the presence of a biofilm. The addition of immune cells to this established system will expand the understanding of host-pathogen interactions while ensuring the use of standardized and optimized conditions to measure these processes accurately.
2022-12-14T20:15:47Z
2022-12-14T20:15:47Z
2022-12-14T20:15:47Z
2022-06-08
Article - Refereed
1940-087X
http://hdl.handle.net/10919/112888
https://doi.org/10.3791/63773
184
Gloag, Erin [0000-0001-8895-3444]
35758715
1940-087X
en
https://www.ncbi.nlm.nih.gov/pubmed/35758715
http://creativecommons.org/licenses/by-nc-nd/4.0/
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
MyJove Corporation
oai:vtechworks.lib.vt.edu:10919/978602020-10-13T19:02:47Zcom_10919_24259com_10919_5559col_10919_24342
Ancient, globally distributed lineage of Sarcocystis from sporocysts of the Eastern rat snake (Pantherophis alleghaniensis) and its relation to neurological sequalae in intermediate hosts
Verma, Shiv K.
Lindsay, David S.
Rosenthal, Benjamin M.
Dubey, Jitender P.
Sarcocystis
Rat snake
Mice
Host
Bioassay
There is an emerging concern that snakes are definitive hosts of certain species of Sarcocystis that cause muscular sarcocystosis in human and non-human primates. Other species of Sarcocystis are known to cycle among snakes and rodents, but have been poorly characterized in the USA and elsewhere. Although neurological sequalae are known for certain species of Sarcocystis, no such neurological symptoms are known to typify parasites that naturally cycle in rodents. Here, sporocysts of a species of Sarcocystis were found in the intestinal contents of a rat snake (Pantherophis alleghaniensis) from Maryland, USA. The sporocysts were orally infective for interferon gamma gene knockout (KO) mice, but not to Swiss Webster outbred mice. The KO mice developed neurological signs, and were necropsied between 33 and 52 days post-inoculation. Only schizonts/merozoites were found, and they were confined to the brain. The predominant lesion was meningoencephalitis characterized by perivascular cuffs, granulomas, and necrosis of the neuropil. The schizonts and merozoites were located in neuropil, and apparently extravascular. Brain homogenates from infected KO mice were infective to KO mice and CV-1 cell line. DNA extracted from the infected mouse brain, and infected cell cultures revealed the highest identity with Sarcocystis species that employ snakes as definitive hosts. This is the first report of Sarcocystis infection in the endangered rat snake (P. alleghaniensis) and the first report of neurological sarcocystosis in mice induced by feeding sporocysts from a snake. These data underscore the likelihood that parasites in this genus that employ snakes as their definitive hosts constitute an ancient, globally distributed monophyletic group. These data also raise the possibility that neurological sequalae may be more common in intermediate hosts of Sarcocystis spp. than has previously been appreciated.
2020-04-21T18:12:40Z
2020-04-21T18:12:40Z
2020-04-21T18:12:40Z
2016-07
Article - Refereed
0932-0113
http://hdl.handle.net/10919/97860
https://doi.org/10.1007/s00436-016-5086-2
115
7
27130321
1432-1955
en
http://creativecommons.org/publicdomain/zero/1.0/
Creative Commons CC0 1.0 Universal Public Domain Dedication
oai:vtechworks.lib.vt.edu:10919/751272023-06-14T17:50:14Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559com_10919_24261com_10919_111086com_10919_5532col_10919_70873col_10919_24342col_10919_24343col_10919_111087
Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency
Lei, Shaohua
Ryu, Junghyun
Wen, Ke
Twitchell, Erica
Bui, Tammy
Ramesh, Ashwin
Weiss, Mariah
Li, Guohua
Samuel, Helen
Clark-Deener, Sherrie
Jiang, Xi
Lee, Kiho
Yuan, Lijuan
Animal and Poultry Sciences
Biomedical Sciences and Pathobiology
Large Animal Clinical Sciences
blood group antigen
one-step generation
in-vivo
immunocompromised patients
vaccine development
united-states
knockout pigs
b-cells
gastroenteritis
gene
Application of genetically engineered (GE) large animals carrying multi-allelic modifications has been hampered by low efficiency in production and extended gestation period compared to rodents. Here, we rapidly generated RAG2/IL2RG double knockout pigs using direct injection of CRISPR/Cas9 system into developing embryos. RAG2/IL2RG deficient pigs were immunodeficient, characterized by depletion of lymphocytes and either absence of or structurally abnormal immune organs. Pigs were maintained in gnotobiotic facility and evaluated for human norovirus (HuNoV) infection. HuNoV shedding lasted for 16 days in wild type pigs, compared to 27 days (until the end of trials) in RAG2/IL2RG deficient pigs. Additionally, higher HuNoV titers were detected in intestinal tissues and contents and in blood, indicating increased and prolonged HuNoV infection in RAG2/IL2RG deficient pigs and the importance of lymphocytes in HuNoV clearance. These results suggest that GE immunodeficient gnotobiotic pigs serve as a novel model for biomedical research and will facilitate HuNoV studies.
2017-02-22T15:40:30Z
2017-02-22T15:40:30Z
2017-02-22T15:40:30Z
2016-04-27
Article - Refereed
2045-2322
http://hdl.handle.net/10919/75127
https://doi.org/10.1038/srep25222
6
Clark-Deener, S [0000-0002-6620-0625]
Yuan, Lijuan [0000-0003-0709-5228]
en
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000374857900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Nature Publishing Group
oai:vtechworks.lib.vt.edu:10919/1125572022-11-11T08:14:42Zcom_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_78882col_10919_24342
Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection
Artman, Chad
Idegwu, Nnebuefe
Brumfield, Kyle D.
Lai, Ken
Hauta, Shirley
Falzarano, Darryl
Parreño, Viviana
Yuan, Lijuan
Geyer, James D.
Goepp, Julius G.
Background: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model. Methods: Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model. Results: IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:2<sup>21</sup> (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (<i>p</i> < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (<i>p</i> < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6. Conclusions: We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway.
2022-11-10T18:24:24Z
2022-11-10T18:24:24Z
2022-11-10T18:24:24Z
2022-10-27
Article - Refereed
Artman, C.; Idegwu, N.; Brumfield, K.D.; Lai, K.; Hauta, S.; Falzarano, D.; Parreño, V.; Yuan, L.; Geyer, J.D.; Goepp, J.G. Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection. Viruses 2022, 14, 2371.
http://hdl.handle.net/10919/112557
https://doi.org/10.3390/v14112371
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/1067072023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_23829com_10919_5553com_10919_24259com_10919_5559com_10919_91913com_10919_23198com_10919_91912col_10919_70873col_10919_23830col_10919_24342col_10919_91914col_10919_91916
Adenovirus transduction to express human ACE2 causes obesity-specific morbidity in mice, impeding studies on the effect of host nutritional status on SARS-CoV-2 pathogenesis
Rai, Pallavi
Chuong, Christina
LeRoith, Tanya
Smyth, James W.
Panov, Julia
Levi, Moshe
Kehn-Hall, Kylene
Duggal, Nisha K.
Weger-Lucarelli, James
Life Sciences & Biomedicine
Virology
COVID-19
Diet-induced obesity
hACE2
Replication-defective adenovirus
Tissue
Pathology
ACUTE RESPIRATORY SYNDROME
SYNDROME CORONAVIRUS INFECTION
IMMUNE-RESPONSES
MORTALITY
SARS
Virology
06 Biological Sciences
07 Agricultural and Veterinary Sciences
11 Medical and Health Sciences
The COVID-19 pandemic has paralyzed the global economy and resulted in millions of deaths globally. People with co-morbidities like obesity, diabetes and hypertension are at an increased risk for severe COVID-19 illness. This is of overwhelming concern because 42% of Americans are obese, 30% are pre-diabetic and 9.4% have clinical diabetes. Here, we investigated the effect of obesity on disease severity following SARS-CoV-2 infection using a well-established mouse model of diet-induced obesity. Diet-induced obese and lean control C57BL/6 N mice, transduced for ACE2 expression using replication-defective adenovirus, were infected with SARS-CoV-2, and monitored for lung pathology, viral titers, and cytokine expression. No significant differences in tissue pathology or viral replication was observed between AdV transduced lean and obese groups, infected with SARS-CoV-2, but certain cytokines were expressed more significantly in infected obese mice compared to the lean ones. Notably, significant weight loss was observed in obese mice treated with the adenovirus vector, independent of SARS-CoV-2 infection, suggesting an obesity-dependent morbidity induced by the vector. These data indicate that the adenovirus-transduced mouse model of SARS-CoV-2 infection, as described here and elsewhere, may be inappropriate for nutrition studies.
2021-11-22T17:41:00Z
2021-11-22T17:41:00Z
2021-11-22T17:41:00Z
2021-11-01
Article - Refereed
0042-6822
S0042-6822(21)00184-7 (PII)
http://hdl.handle.net/10919/106707
https://doi.org/10.1016/j.virol.2021.08.014
563
Duggal, Nisha [0000-0002-9893-8069]
Kehn-Hall, Kylene [0000-0001-8036-7213]
LeRoith, Tanya [0000-0002-1196-6949]
34509029
1089-862X
en
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000700278300004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
Elsevier
oai:vtechworks.lib.vt.edu:10919/958122022-02-26T00:17:13Zcom_10919_24259com_10919_5559col_10919_24342
The genetic ancestry of American Creole cattle inferred from uniparental and autosomal genetic markers
Ginja, Catarina
Gama, Luis Telo
Cortes, Oscar
Martin Burriel, Inmaculada
Luis Vega-Pla, Jose
Penedo, Cecilia
Sponenberg, D. Phillip
Canon, Javier
Sanz, Arianne
do Egito, Andrea Alves
Angela Alvarez, Luz
Giovambattista, Guillermo
Agha, Saif
Rogberg-Munoz, Andres
Cassiano Lara, Maria Aparecida
Delgado Bermejo, Juan Vicente
Martínez, Amparo
Afonso, Sonia
Aguirre, Lenin
Armstrong, Eileen
Camacho Vallejo, María Esperanza
Canales, Amado
Cassama, Bernardo
Contreras, Gloria
Moras Cordeiro, J. M.
Dunner, Susana
Elbeltagy, Ahmed
Soares Fioravanti, Maria Clorinda
Gomez Carpio, Mayra
Gomez, Mariano
Hernandez, Antonio
Hernandez, Darwin
Juliano, Raquel Soares
Landi, Vincenzo
Marques, Ribamar
Martinez, Ruben D.
Roberto Martinez, O.
Melucci, Lilia
Molina Flores, Baldomero
Mujica, Fernando
Pares i Casanova, Pere-Miquel
Quiroz, Jorge
Rodellar, Clementina
Tjon, Gerald
Adebambo, Tumininu
Uffo, Odalys
Cesar Vargas, Julio
Villalobos, Axel
Zaragoza, Pilar
Cattle imported from the Iberian Peninsula spread throughout America in the early years of discovery and colonization to originate Creole breeds, which adapted to a wide diversity of environments and later received influences from other origins, including zebu cattle in more recent years. We analyzed uniparental genetic markers and autosomal microsatellites in DNA samples from 114 cattle breeds distributed worldwide, including 40 Creole breeds representing the whole American continent, and samples from the Iberian Peninsula, British islands, Continental Europe, Africa and American zebu. We show that Creole breeds differ considerably from each other, and most have their own identity or group with others from neighboring regions. Results with mtDNA indicate that T1c-lineages are rare in Iberia but common in Africa and are well represented in Creoles from Brazil and Colombia, lending support to a direct African influence on Creoles. This is reinforced by the sharing of a unique Y-haplotype between cattle from Mozambique and Creoles from Argentina. Autosomal microsatellites indicate that Creoles occupy an intermediate position between African and European breeds, and some Creoles show a clear Iberian signature. Our results confirm the mixed ancestry of American Creole cattle and the role that African cattle have played in their development.
2019-11-19T18:42:58Z
2019-11-19T18:42:58Z
2019-11-19T18:42:58Z
2019-08-07
Article - Refereed
11486
http://hdl.handle.net/10919/95812
https://doi.org/10.1038/s41598-019-47636-0
9
31391486
2045-2322
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Springer Nature
oai:vtechworks.lib.vt.edu:10919/972342022-02-26T00:17:13Zcom_10919_24259com_10919_5559col_10919_24342
Confirmation of Sarcocystis jamaicensis Sarcocysts in IFN-γ Gene Knockout Mice Orally Inoculated With Sporocysts From a Red-Tailed Hawk (Buteo jamaicensis)
Dubey, Jitender P.
Cerqueira-Cezar, Camila K.
Murata, Fernando H. A.
Mowery, J. D.
Scott, D.
von Dohlen, Alexa Rosypal
Lindsay, David S.
Sarcocystis
Transmission Electron Microscopy
Mus musculus
Sarcocystis jamaicensis
Merozoites
Schizonts
Encephalitis
Red-Tailed Hawk
Buteo jamaicensis
Sporocysts
Here, we report confirmation of sarcocysts of Sarcocystis jamaicensis in an experimental intermediate host, IFN-gamma gene knockout (KO) mice orally inoculated sporocysts from its natural definitive host, a red-tailed hawk (Buteo jamaicensis) (RTH). A RTH submitted to the Carolina Raptor Center, Huntersville, North Carolina, was euthanized because it could not be rehabilitated and released. Fully sporulated sporocysts from intestinal scrapings of the RTH were orally fed to 2 laboratory-reared outbred Swiss Webster mice (SW; Mus musculus) and to 2 KO mice. The sporocysts were infective for KO mice but not to SW mice. Both SW mice remained asymptomatic, and neither schizonts nor sarcocysts were found in their tissues when euthanized on day 54 post-inoculation (PI). The KO mice developed neurological signs and were necropsied 38-54 days PI. Schizonts/merozoites were found in both KO mice euthanized and they were confined to the brain. The predominant lesion was meningoencephalitis. Microscopic sarcocysts were found in muscles of both KO mice. When viewed with light microscopy, the sarcocyst wall appeared thin (<1 mu m thick) and smooth. Ultrastructural details of sarcocysts are described.
2020-03-06T17:57:00Z
2020-03-06T17:57:00Z
2020-03-06T17:57:00Z
2019-02-22
Article - Refereed
0022-3395
http://hdl.handle.net/10919/97234
https://doi.org/10.1645/18-148
105
1
30807718
1937-2345
en
http://creativecommons.org/publicdomain/zero/1.0/
Creative Commons CC0 1.0 Universal Public Domain Dedication
oai:vtechworks.lib.vt.edu:10919/1000242023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections
Thangamani, Shankar
Younis, Waleed
Seleem, Mohamed N.
SOFT-TISSUE INFECTIONS
CA-MRSA SKIN
IN-VITRO
AUREUS
ANTIBIOTICS
ANTIOXIDANT
INFLAMMATION
EXPRESSION
COMPOUND
DRUGS
Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections.
2020-09-21T16:11:54Z
2020-09-21T16:11:54Z
2020-09-21T16:11:54Z
2015-06-26
Article - Refereed
2045-2322
srep11596 (PII)
http://hdl.handle.net/10919/100024
https://doi.org/10.1038/srep11596
5
1
Seleem, Mohamed [0000-0003-0939-0458]
26111644 (pubmed)
2045-2322
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Nature Publishing Group
oai:vtechworks.lib.vt.edu:10919/966742023-11-29T19:07:11Zcom_10919_5540com_10919_24259com_10919_5559com_10919_84995com_10919_5553col_10919_71752col_10919_24342col_10919_84996
PINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosis
Sarraf, Shireen A.
Sideris, Dionisia P.
Giagtzoglou, Nikolaos
Artavanis-Tsakonas, Spyros
Youle, Richard J.
Pickrell, Alicia M.
Biomedical Sciences and Pathobiology
School of Neuroscience
PINK1 and Parkin are established mediators of mitophagy, the selective removal of damaged mitochondria by autophagy. PINK1 and Parkin have been proposed to act as tumor suppressors, as loss-of-function mutations are correlated with enhanced tumorigenesis. However, it is unclear how PINK1 and Parkin act in coordination during mitophagy to influence the cell cycle. Here we show that PINK1 and Parkin genetically interact with proteins involved in cell cycle regulation, and loss of PINK1 and Parkin accelerates cell growth. PINK1- and Parkin-mediated activation of TBK1 at the mitochondria during mitophagy leads to a block in mitosis due to the sequestration of TBK1 from its physiological role at centrosomes during mitosis. Our study supports a diverse role for the far-reaching, regulatory effects of mitochondrial quality control in cellular homeostasis and demonstrates that the PINK1/Parkin pathway genetically interacts with the cell cycle, providing a framework for understanding the molecular basis linking PINK1 and Parkin to mitosis.
2020-02-03T17:44:45Z
2020-02-03T17:44:45Z
2020-02-03T17:44:45Z
2019-10-01
Article - Refereed
Sarraf et al., 2019, Cell Reports 29, 225–235 October 1, 2019 ª 2019 The Author(s). https://doi.org/10.1016/j.celrep.2019.08.085
http://hdl.handle.net/10919/96674
https://doi.org/10.1016/j.celrep.2019.08.085
29
en
http://creativecommons.org/licenses/by-nc-nd/4.0/
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Cell Press
oai:vtechworks.lib.vt.edu:10919/1049312023-12-12T14:54:57Zcom_10919_24259com_10919_5559com_10919_24263col_10919_24342col_10919_24345
Presumptive Identification of Smooth Brucella Strain Antibodies in Canines
Helms, Alyssa B.
Balogh, Orsolya
Franklin-Guild, Rebecca
Lahmers, Kevin K.
Caswell, Clayton C.
Small Animal Clinical Sciences
brucellosis
canine
abortus
smooth
seroprevalence
antibodies
suis
Brucellosis is a zoonotic disease caused by a Gram-negative coccobacillus. There are four Brucella strains of zoonotic importance in our domestic species, subdivided by their culture phenotypes: Brucella abortus (B. abortus), B. melitensis, B. suis (smooth strains) and B. canis (rough strain). Dogs can serve as hosts for all four of the zoonotic strains; however, routine serologic testing in dogs has been limited to the identification of B. canis antibodies. The aim of our study was to identify smooth Brucella strain antibodies in canines. We hypothesize that the Brucella abortus Fluorescence Polarization Assay would be successful in identifying smooth Brucella strain antibodies in canines. Ninety-five dogs, including forty-five hog hunting dogs were screened for circulating antibodies to any of the four zoonotic strains of the bacteria utilizing a combination of Canine Brucella Slide Agglutination Test (CBSA), Brucella canis Agar Gel Immunodiffusion II test (AGIDII), Brucella abortus Card Agglutination Test (BCA), and the Brucella abortus Fluorescence Polarization Assay (FPA). Test interpretation results yielded a 0% (0/95) smooth Brucella strain seropositivity rate, with 2% (2/95) of dogs yielding inconclusive rough Brucella strain serology results (0–2% rough strain seropositivity rate). Additionally, a retrospective portion of the study was performed to identify sera containing circulating antibodies to any of the smooth strains of Brucella by testing previously banked canine serum samples stored at Cornell’s Veterinary Diagnostic Laboratory from 2018 to 2019 via Brucella abortus FPA. Of the 769 serum samples tested, 13/769 (1.7%) yielded an inconclusive result, 725/769 (94.2%) were negative, 30/769 (4%) yielded a positive FPA test result, and 1/769 (0.1%) had to be excluded due to insufficient sample remaining to perform the diagnostic test. Of the 30 FPA positive canine serum samples, 97% (29/30) also tested positive on the CBSA test. Additionally, there was a statistically significant (p < 0.0001) likelihood of altered (spayed/neutered) and mixed breed dogs to be FPA positive when compared to intact, purebred dogs, respectively.
2021-09-03T17:04:40Z
2021-09-03T17:04:40Z
2021-09-03T17:04:40Z
2021-07-08
Article - Refereed
http://hdl.handle.net/10919/104931
https://doi.org/10.3389/fvets.2021.697479
8
en
http://creativecommons.org/licenses/by/4.0/
Attribution 4.0 International
Frontiers
oai:vtechworks.lib.vt.edu:10919/1121782022-10-18T07:13:16Zcom_10919_24259com_10919_5559col_10919_24342
Wearable adjunct ozone and antibiotic therapy system for treatment of Gram-negative dermal bacterial infection
Roth, Alexander
Maruthamuthu, Murali Kannan
Nejati, Sina
Krishnakumar, Akshay
Selvamani, Vidhya
Sedaghat, Sotoudeh
Nguyen, Juliane
Seleem, Mohamed N.
Rahimi, Rahim
silver nanoparticles
molecular-weight
fiber mats
antibacterial
vancomycin
patch
hydrolysis
resistance
delivery
release
The problematic combination of a rising prevalence of skin and soft tissue infections and the growing rate of life-threatening antibiotic resistant infections presents an urgent, unmet need for the healthcare industry. These evolutionary resistances originate from mutations in the bacterial cell walls which prevent effective diffusion of antibiotics. Gram-negative bacteria are of special consideration due to the natural resistance to many common antibiotics due to the unique bilayer structure of the cell wall. The system developed here provides one solution to this problem through a wearable therapy that delivers and utilizes gaseous ozone as an adjunct therapy with topical antibiotics through a novel dressing with drug-eluting nanofibers (NFs). This technology drastically increases the sensitivity of Gram-negative bacteria to common antibiotics by using oxidative ozone to bypass resistances created by the bacterial cell wall. To enable simple and effective application of adjunct therapy, ozone delivery and topical antibiotics have been integrated into a single application patch. The drug delivery NFs are generated via electrospinning in a fast-dissolve PVA mat without inducing decreasing gas permeability of the dressing. A systematic study found ozone generation at 4 mg/h provided optimal ozone levels for high antimicrobial performance with minimal cytotoxicity. This ozone treatment was used with adjunct therapy delivered by the system in vitro. Results showed complete eradication of Gram-negative bacteria with ozone and antibiotics typically used only for Gram-positive bacteria, which showed the strength of ozone as an enabling adjunct treatment option to sensitize bacteria strains to otherwise ineffective antibiotics. Furthermore, the treatment is shown through biocompatibility testing to exhibit no cytotoxic effect on human fibroblast cells.
2022-10-17T12:51:25Z
2022-10-17T12:51:25Z
2022-10-17T12:51:25Z
2022-08-17
Article - Refereed
2045-2322
13927
http://hdl.handle.net/10919/112178
https://doi.org/10.1038/s41598-022-17495-3
12
1
35977975
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Nature Portfolio
oai:vtechworks.lib.vt.edu:10919/1000322023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Ospemifene displays broad-spectrum synergistic interactions with itraconazole through potent interference with fungal efflux activities
Eldesouky, Hassan E.
Salama, Ehab A.
Hazbun, Tony R.
Mayhoub, Abdelrahman S.
Seleem, Mohamed N.
CANDIDA-ALBICANS STRAINS
AZOLE RESISTANCE
IN-VITRO
INVASIVE CANDIDIASIS
ANTIFUNGAL ACTIVITY
AMPHOTERICIN-B
CHALLENGES
CASPOFUNGIN
FLUCONAZOLE
PREVALENCE
Azole antifungals are vital therapeutic options for treating invasive mycotic infections. However, the emergence of azole-resistant isolates combined with limited therapeutic options presents a growing challenge in medical mycology. To address this issue, we utilized microdilution checkerboard assays to evaluate nine stilbene compounds for their ability to interact synergistically with azole drugs, particularly against azole-resistant fungal isolates. Ospemifene displayed the most potent azole chemosensitizing activity, and its combination with itraconazole displayed broad-spectrum synergistic interactions against Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus (ΣFICI = 0.05–0.50). Additionally, in a Caenorhabditis elegans infection model, the ospemifene-itraconazole combination significantly reduced fungal CFU burdens in infected nematodes by ~75–96%. Nile Red efflux assays and RT-qPCR analysis suggest ospemifene interferes directly with fungal efflux systems, thus permitting entry of azole drugs into fungal cells. This study identifies ospemifene as a novel antifungal adjuvant that augments the antifungal activity of itraconazole against a broad range of fungal pathogens.
2020-09-21T16:14:29Z
2020-09-21T16:14:29Z
2020-09-21T16:14:29Z
2020-04-08
Article - Refereed
2045-2322
10.1038/s41598-020-62976-y (PII)
http://hdl.handle.net/10919/100032
https://doi.org/10.1038/s41598-020-62976-y
10
1
Seleem, Mohamed [0000-0003-0939-0458]
32269301 (pubmed)
2045-2322
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Nature Publishing Group
oai:vtechworks.lib.vt.edu:10919/854602023-04-14T17:49:42Zcom_10919_24259com_10919_5559col_10919_24342
Catalytic Nanoceria Are Preferentially Retained in the Rat Retina and Are Not Cytotoxic after Intravitreal Injection
Wong, Lily L.
Hirst, Suzanne M.
Pye, Quentin N.
Reilly, Christopher M.
Seal, Sudipta
McGinnis, James F.
Cerium oxide nanoparticles (nanoceria) possess catalytic and regenerative radical scavenging activities. The ability of nanoceria to maintain cellular redox balance makes them ideal candidates for treatment of retinal diseases whose development is tightly associated with oxidative damage. We have demonstrated that our stable water-dispersed nanoceria delay photoreceptor cell degeneration in rodent models and prevent pathological retinal neovascularization in vldlr mutant mice. The objectives of the current study were to determine the temporal and spatial distributions of nanoceria after a single intravitreal injection, and to determine if nanoceria had any toxic effects in healthy rat retinas. Using inductively-coupled plasma mass spectrometry (ICP-MS), we discovered that nanoceria were rapidly taken up by the retina and were preferentially retained in this tissue even after 120 days. We also did not observe any acute or long-term negative effects of nanoceria on retinal function or cytoarchitecture even after this long-term exposure. Because nanoceria are effective at low dosages, nontoxic and are retained in the retina for extended periods, we conclude that nanoceria are promising ophthalmic therapeutics for treating retinal diseases known to involve oxidative stress in their pathogeneses.
2018-10-23T17:18:38Z
2018-10-23T17:18:38Z
2018-10-23T17:18:38Z
2013-03-11
Article - Refereed
e58431
http://hdl.handle.net/10919/85460
https://doi.org/10.1371/journal.pone.0058431
8
3
23536794
1932-6203
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
PLOS
oai:vtechworks.lib.vt.edu:10919/955642023-11-29T19:07:13Zcom_10919_8195com_10919_25799com_10919_5540com_10919_24259com_10919_5559com_10919_23842com_10919_5553com_10919_23261com_10919_5539com_10919_84995com_10919_91896com_10919_25796col_10919_18629col_10919_71752col_10919_24342col_10919_23843col_10919_23262col_10919_84996col_10919_91897
Peripheral loss of EphA4 ameliorates TBI-induced neuroinflammation and tissue damage
Kowalski, Elizabeth A.
Chen, Jiang
Hazy, Amanda
Fritsch, Lauren E.
Gudenschwager-Basso, Erwin K.
Chen, Michael
Wang, Xia
Qian, Yun
Zhou, Mingjun
Byerly, Matthew
Pickrell, Alicia M.
Matson, John B.
Allen, Irving C.
Theus, Michelle H.
Mechanical Engineering
Biomedical Sciences and Pathobiology
Chemistry
School of Neuroscience
Center for Drug Discovery
Background
The continuum of pro- and anti-inflammatory response elicited by traumatic brain injury (TBI) is suggested to play a key role in the outcome of TBI; however, the underlying mechanisms remain ill -defined.
Methods
Here, we demonstrate that using bone marrow chimeric mice and systemic inhibition of EphA4 receptor shifts the pro-inflammatory milieu to pro-resolving following acute TBI.
Results
EphA4 expression is increased in the injured cortex as early as 2 h post-TBI and on CX3CR1gfp-positive cells in the peri-lesion. Systemic inhibition or genetic deletion of EphA4 significantly reduced cortical lesion volume and shifted the inflammatory profile of peripheral-derived immune cells to pro-resolving in the damaged cortex. These findings were consistent with in vitro studies showing EphA4 inhibition or deletion altered the inflammatory state of LPS-stimulated monocyte/macrophages towards anti-inflammatory. Phosphoarray analysis revealed that EphA4 may regulate pro-inflammatory gene expression by suppressing the mTOR, Akt, and NF-κB pathways. Our human metadata analysis further demonstrates increased EPHA4 and pro-inflammatory gene expression, which correlates with reduced AKT concurrent with increased brain injury severity in patients.
Conclusions
Overall, these findings implicate EphA4 as a novel mediator of cortical tissue damage and neuroinflammation following TBI.
2019-11-18T13:02:47Z
2019-11-18T13:02:47Z
2019-11-18T13:02:47Z
2019-11-11
Article - Refereed
Journal of Neuroinflammation. 2019 Nov 11;16(1):210
http://hdl.handle.net/10919/95564
https://doi.org/10.1186/s12974-019-1605-2
en
http://creativecommons.org/licenses/by/4.0/
The Author(s)
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/1162652023-09-13T07:11:27Zcom_10919_24259com_10919_5559col_10919_24342
Targeting Enterococcus faecalis HMG-CoA reductase with a non-statin inhibitor
Bose, Sucharita
Steussy, C. Nicklaus
Lopez-Perez, Daneli
Schmidt, Tim
Kulathunga, Samadhi C.
Seleem, Mohamed N.
Lipton, Mark
Mesecar, Andrew D.
Rodwell, Victor W.
Stauffacher, Cynthia V.
vancomycin-resistant enterococcus
coenzyme-a reductase
crystal-structure
catalytic portion
hydride transfer
binding fold
domain
biosynthesis
specificity
essentiality
High-throughput in vitro screening and crystal structures identify a non-statin inhibitor of HMG-CoA reductase for novel antibacterial drug design. HMG-CoA reductase (HMGR), a rate-limiting enzyme of the mevalonate pathway in Gram-positive pathogenic bacteria, is an attractive target for development of novel antibiotics. In this study, we report the crystal structures of HMGR from Enterococcus faecalis (efHMGR) in the apo and liganded forms, highlighting several unique features of this enzyme. Statins, which inhibit the human enzyme with nanomolar affinity, perform poorly against the bacterial HMGR homologs. We also report a potent competitive inhibitor (Chembridge2 ID 7828315 or compound 315) of the efHMGR enzyme identified by a high-throughput, in-vitro screening. The X-ray crystal structure of efHMGR in complex with 315 was determined to 1.27 angstrom resolution revealing that the inhibitor occupies the mevalonate-binding site and interacts with several key active site residues conserved among bacterial homologs. Importantly, 315 does not inhibit the human HMGR. Our identification of a selective, non-statin inhibitor of bacterial HMG-CoA reductases will be instrumental in lead optimization and development of novel antibacterial drug candidates.
2023-09-12T14:31:15Z
2023-09-12T14:31:15Z
2023-09-12T14:31:15Z
2023-04
Article - Refereed
360
http://hdl.handle.net/10919/116265
https://doi.org/10.1038/s42003-023-04639-y
6
1
37012403
2399-3642
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Nature Portfolio
oai:vtechworks.lib.vt.edu:10919/1074292022-06-17T20:03:39Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Incidental diagnosis of a spindle cell type gastrointestinal stromal tumor in a dog with ethylene glycol intoxication
Serpa, Priscila B. S.
Santos, Andrea P.
Life Sciences & Biomedicine
Veterinary Sciences
canine
CD117
cytology
GIST
immunohistochemistry
neoplasia
NIMT
EXPRESSION
0608 Zoology
0707 Veterinary Sciences
A 6-year-old castrated male American Pit Bull Terrier dog was presented for evaluation of acute onset of tonic-clonic seizures, anorexia, and vomiting. On physical examination, neurologic signs, such as generalized proprioceptive ataxia, salivation, circling to the right, and absent patellar reflexes bilaterally, were noted. A complete blood cell count revealed mild hemoconcentration and an inflammatory leukogram, while a chemistry panel showed severe azotemia, marked hypochloremia, and a severe titrational metabolic acidosis, suggesting possible ethylene glycol intoxication. However, an irregularly round, small mass was identified in the large intestine on abdominal ultrasound. Additionally, bilateral hyperechoic renal cortices with medullary rim sign were suggestive of acute nephritis or tubular necrosis. The cytologic evaluation of a fine-needle aspiration biopsy of the abdominal mass revealed a large population of mesenchymal cells, suggesting the presence of neoplasia. Due to the worsening of symptoms, the dog was humanely euthanized. Necropsy confirmed ethylene glycol intoxication, and the incidental finding of a neoplastic intestinal mass was diagnosed as spindle cell sarcoma. Immunohistochemical staining showed strong, diffuse positivity for CD117, smooth muscle actin, and S-100, indicating the final diagnosis of a spindle cell type gastrointestinal stromal tumor (GIST). This report briefly discusses the classifications of nonlymphoid, nonangiogenic intestinal mesenchymal tumors, characteristics of GISTs, and the importance of the immunohistochemical classification of mesenchymal tumors of the gastrointestinal tract.
2022-01-06T17:03:46Z
2022-01-06T17:03:46Z
2022-01-06T17:03:46Z
2021-11-21
Article - Refereed
0275-6382
http://hdl.handle.net/10919/107429
https://doi.org/10.1111/vcp.13063
da Silva Serpa, Priscila Beatriz [0000-0001-6073-2172]
34806207
1939-165X
en
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000720780200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
Wiley
oai:vtechworks.lib.vt.edu:10919/1041782023-11-29T19:24:58Zcom_10919_78629com_10919_78628com_10919_5540com_10919_24226com_10919_5532com_10919_24259com_10919_5559com_10919_91436col_10919_78630col_10919_71806col_10919_24301col_10919_24342col_10919_97229
A selective sweep in the Spike gene has driven SARS-CoV-2 human adaptation
Kang, Lin
He, Guijuan
Sharp, Amanda K.
Wang, Xiaofeng
Brown, Anne M.
Michalak, Pawel
Weger-Lucarelli, James
While SARS-CoV-2 likely has animal origins, the viral genetic changes necessary to adapt this animal-derived ancestral virus to humans are largely unknown, mostly due to low levels of sequence polymorphism and the notorious difficulties in experimental manipulations of coronavirus genomes. We scanned more than 182,000 SARS-CoV-2 genomes for selective sweep signatures and found that a distinct footprint of positive selection is located around a non-synonymous change (A1114G; T372A) within the Receptor-Binding Domain of the Spike protein, which likely played a critical role in overcoming species barriers and accomplishing interspecies transmission from animals to humans. Structural analysis indicated that the substitution of threonine with an alanine in SARS-CoV-2 concomitantly removes a predicted glycosylation site at N370, resulting in more favorable binding predictions to human ACE2, the cellular receptor. Using a novel bacteria-free cloning system for manipulating RNA virus genomes, we experimentally validated that this SARS-CoV-2-unique substitution significantly increases replication in human cells relative to its putative ancestral variant. Notably, this mutation’s impact on virus replication in human cells was much greater than that of the Spike D614G mutant, which has been widely reported to have been selected for during human-to-human transmission.
2021-07-15T15:19:38Z
2021-07-15T15:19:38Z
2021-07-15T15:19:38Z
2021-03-05
Article
http://hdl.handle.net/10919/104178
https://doi.org/10.1101/2021.02.13.431090
en
http://creativecommons.org/licenses/by-nc-nd/4.0/
Attribution-NonCommercial-NoDerivatives 4.0 International
Virginia Tech
oai:vtechworks.lib.vt.edu:10919/1174042024-01-20T03:00:44Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
An Interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and Swine: A Case Study on Flunixin, Florfenicol, and Penicillin G
Chou, Wei-Chun
Tell, Lisa A.
Baynes, Ronald E.
Davis, Jennifer L.
Maunsell, Fiona P.
Riviere, Jim E.
Lin, Zhoumeng
drug residue
Food Animal Residue Avoidance Databank (FARAD)
food safety
interactive generic physiologically based pharmacokinetic (igPBPK) model
withdrawal interval (WDI)
Violative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically based pharmacokinetic (PBPK) models for estimating withdrawal intervals (WDIs) for extralabel prescribed drugs in food animals. Existing models are insufficient to address the food safety concern as these models are either limited to 1 specific drug or difficult to be used by non-modelers. This study aimed to develop a user-friendly generic PBPK platform that can predict tissue residues and estimate WDIs for multiple drugs including flunixin, florfenicol, and penicillin G in cattle and swine. Mechanism-based in silico methods were used to predict tissue/plasma partition coefficients and the models were calibrated and evaluated with pharmacokinetic data from Food Animal Residue Avoidance Databank (FARAD). Results showed that model predictions were, in general, within a 2-fold factor of experimental data for all 3 drugs in both species. Following extralabel administration and respective U.S. FDA-approved tolerances, predicted WDIs for both cattle and swine were close to or slightly longer than FDA-approved label withdrawal times (eg, predicted 8, 28, and 7 days vs labeled 4, 28, and 4 days for flunixin, florfenicol, and penicillin G in cattle, respectively). The final model was converted to a web-based interactive generic PBPK platform. This PBPK platform serves as a user-friendly quantitative tool for real-time predictions of WDIs for flunixin, florfenicol, and penicillin G following FDA-approved label or extralabel use in both cattle and swine, and provides a basis for extrapolating to other drugs and species.
2024-01-19T13:22:02Z
2024-01-19T13:22:02Z
2024-01-19T13:22:02Z
2022-07-28
Article - Refereed
1096-6080
6596615 (PII)
https://hdl.handle.net/10919/117404
https://doi.org/10.1093/toxsci/kfac056
188
2
Davis, Jennifer [0000-0002-7930-4589]
35642931
1096-0929
en
https://www.ncbi.nlm.nih.gov/pubmed/35642931
http://creativecommons.org/licenses/by-nc/4.0/
Creative Commons Attribution-NonCommercial 4.0 International
Oxford University Press
oai:vtechworks.lib.vt.edu:10919/740462023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Plexin-B2 and Plexin-D1 in Dendritic Cells: Expression and IL-12/IL-23p40 Production
Holl, Eda K.
Roney, Kelly E.
Allen, Irving C.
Steinbach, Erin
Arthur, Janelle C.
Buntzman, Adam
Plevy, Scott
Frelinger, Jeffrey
Ting, Jenny P.-Y.
iv semaphorin cd100
nonredundant roles
immune-responses
b-cell
family
growth
receptors
guidance
system
sema4a
Plexins are a family of genes (A,B,C, and D) that are expressed in many organ systems. Plexins expressed in the immune system have been implicated in cell movement and cell-cell interaction during the course of an immune response. In this study, the expression pattern of Plexin-B2 and Plexin-D1 in dendritic cells (DCs), which are central in immune activation, was investigated. Plexin-B2 and Plexin-D1 are reciprocally expressed in myeloid and plasmacytoid DC populations. Plasmacytoid DCs have high Plexin-B2 but low Plexin-D1, while the opposite is true of myeloid DCs. Expression of Plexin-B2 and Plexin-D1 is modulated upon activation of DCs by TLR ligands, TNFa, and anti-CD40, again in a reciprocal fashion. Semaphorin3E, a ligand for Plexin-D1 and Plexin-B2, is expressed by T cells, and interestingly, is dramatically higher on Th2 cells and on DCs. The expression of Plexins and their ligands on DCs and T cells suggest functional relevance. To explore this, we utilized chimeric mice lacking Plxnb2 or Plxnd1. Absence of Plexin-B2 and Plexin-D1 on DCs did not affect the ability of these cells to upregulate costimulatory molecules or the ability of these cells to activate antigen specific T cells. Additionally, Plexin-B2 and Plexin-D1 were dispensable for chemokine-directed in-vitro migration of DCs towards key DC chemokines, CXCL12 and CCL19. However, the absence of either Plexin-B2 or Plexin-D1 on DCs leads to constitutive expression of IL-12/IL-23p40. This is the first report to show an association between Plexin-B2 and Plexin-D1 with the negative regulation of IL-12/IL-23p40 in DCs. This work also shows the presence of Plexin-B2 and Plexin-D1 on mouse DC subpopulations, and indicates that these two proteins play a role in IL-12/IL-23p40 production that is likely to impact the immune response.
2017-01-10T00:50:10Z
2017-01-10T00:50:10Z
2017-01-10T00:50:10Z
2012-08-15
Article - Refereed
1932-6203
http://hdl.handle.net/10919/74046
https://doi.org/10.1371/journal.pone.0043333
7
8
en
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000307823600069&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
PLOS
oai:vtechworks.lib.vt.edu:10919/1175462024-01-26T08:00:40Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559com_10919_25796com_10919_111086com_10919_5532com_10919_84995com_10919_5553col_10919_70873col_10919_24342col_10919_25797col_10919_111087col_10919_84996
Sex linked behavioral and hippocampal transcriptomic changes in mice with cell-type specific <i>Egr1</i> loss
Swilley, Cody
Lin, Yu
Zheng, Yuze
Xu, Xiguang
Liu, Min
Jarome, Timothy J.
Hodes, Georgia E.
Xie, Hehuang
sex difference
Egr1
nestin
RNA-seq
hippocampus
behavior
The transcription factor EGR1 is instrumental in numerous neurological processes, encompassing learning and memory as well as the reaction to stress. Egr1 complete knockout mice demonstrate decreased depressive or anxiety-like behavior and impaired performance in spatial learning and memory. Nevertheless, the specific functions of Egr1 in distinct cell types have been largely underexplored. In this study, we cataloged the behavioral and transcriptomic character of Nestin-Cre mediated Egr1 conditional knockout (Egr1cKO) mice together with their controls. Although the conditional knockout did not change nociceptive or anxiety responses, it triggered changes in female exploratory activity during anxiety testing. Hippocampus-dependent spatial learning in the object location task was unaffected, but female Egr1cKO mice did exhibit poorer retention during testing on a contextual fear conditioning task compared to males. RNA-seq data analyses revealed that the presence of the floxed Egr1 cassette or Nestin-Cre driver alone exerts a subtle influence on hippocampal gene expression. The sex-related differences were amplified in Nestin-Cre mediated Egr1 conditional knockout mice and female mice are more sensitive to the loss of Egr1 gene. Differentially expressed genes resulted from the loss of Egr1 in neuronal cell lineage were significantly associated with the regulation of Wnt signaling pathway, extracellular matrix, and axon guidance. Altogether, our results demonstrate that Nestin-Cre and the loss of Egr1 in neuronal cell lineage have distinct impacts on hippocampal gene expression in a sex-specific manner.
2024-01-22T17:44:30Z
2024-01-22T17:44:30Z
2024-01-22T17:44:30Z
2023-10-19
Article - Refereed
1662-4548
PMC10623684
https://hdl.handle.net/10919/117546
https://doi.org/10.3389/fnins.2023.1240209
17
Hodes, Georgia [0000-0002-1551-2178]
37928724
1662-453X
en
https://www.ncbi.nlm.nih.gov/pubmed/37928724
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Frontiers
oai:vtechworks.lib.vt.edu:10919/490472023-12-19T13:34:26Zcom_10919_24259com_10919_5559col_10919_24342
Examination of extraintestinal tissue cysts of Isospora belli
Lindsay, David S.
Dubey, Jitender P.
Toivio-Kinnucan, M. A.
Michiels, J. F.
Blagburn, B. L.
immune-deficiency-syndrome
eimeria-bovis sporozoites
patient
ultrastructure
reactivity
infection
parasites
aids
suis
parasitology
Relapse is common in immunocompetent and immunosuppressed humans infected with Isospora belli and is believed to be associated with the presence of extraintestinal stages. In the present study, we examined this important stage in an AIDS patient using histological, immunohistological, histochemical, and ultrastructural methods to better understand the development and structure of this stage and to develop better means of detecting infections. Antisera made in rabbits to Isospora suis, Toxoplasma gondii, Hammondia hammondi, Sarcocystis neurona, Neospora caninum, and Caryospora bigenetica were tested against I. belli tissue cysts in the avidin-biotin peroxidase complex (ABC) immunohistological test. Most antisera reacted positively in the ABC test at dilutions of 1:100 but not at dilutions of 1:250. Some antisera to N. caninum and H. hammondi reacted positively at dilutions of 1:1,000 in the ABC test. Most reactive antisera stained the tissue cyst wall and not the enclosed zoite. Eight histochemical tests were examined and most were nonreactive with I. belli zoites or tissue cysts. Transmission electron microscopy revealed that the tissue cyst wall was composed of granular material and was directly beneath the parasitophorous vacuole membrane. Zoites were in the center of the tissue cysts and were surrounded by fibrillar material that appeared to originate from the zoite surface. Tubulelike structures were present in the granular tissue cyst wall and in the fibrillar material that surrounded the zoite. Zoites contained a crystalloid body. New findings in the present study consisted of identifying what are probably early tissue cysts that lack a developed tissue cyst wall, demonstrating that more than 1 tissue cyst can occupy a host cell, describing the distribution of micronemes and the shedding of zoite membranes, and identifying tubular structures in the inner tissue cyst wall and inner compartment.
2014-06-20T14:13:14Z
2014-06-20T14:13:14Z
2014-06-20T14:13:14Z
1997-08
Article - Refereed
David S. Lindsay, J. P. Dubey, M. A. Toivio-Kinnucan, J. F. Michiels and Byron L. Blagburn (1997) "Examination of extraintestinal tissue cysts of Isospora belli," The Journal of Parasitology, Vol. 83, No. 4, pp. 620-625. DOI: 10.2307/3284235
0022-3395
http://hdl.handle.net/10919/49047
http://www.jstor.org/stable/3284235
https://doi.org/10.2307/3284235
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/550202023-12-11T11:08:11Zcom_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_18629col_10919_24342col_10919_23146
Recent advances in Brucella abortus vaccines
Dorneles, Elaine Maria S.
Sriranganathan, Nammalwar
Lage, Andrey P.
Brucella abortus vaccines play a central role in bovine brucellosis control/eradication programs and have been successfully used worldwide for decades. Strain 19 and RB51 are the approved B. abortus vaccines strains most commonly used to protect cattle against infection and abortion. However, due to some drawbacks shown by these vaccines much effort has been undertaken for the development of new vaccines, safer and more effective, that could also be used in other susceptible species of animals. In this paper, we present a review of the main aspects of the vaccines that have been used in the brucellosis control over the years and the current research advances in the development of new B. abortus vaccines.
2015-07-31T16:40:32Z
2015-07-31T16:40:32Z
2015-07-31T16:40:32Z
2015-07-08
Article - Refereed
Veterinary Research. 2015 Jul 08;46(1):76
http://hdl.handle.net/10919/55020
https://doi.org/10.1186/s13567-015-0199-7
en
http://creativecommons.org/licenses/by/4.0/
Dorneles et al.
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/1114292023-11-29T19:07:28Zcom_10919_5com_10919_25799com_10919_5540com_10919_24259com_10919_5559com_10919_23765com_10919_24263com_10919_91912com_10919_23198col_10919_70873col_10919_71752col_10919_24342col_10919_24353col_10919_24345col_10919_91916
High intensity focused ultrasound for the treatment of solid tumors: a pilot study in canine cancer patients
Carroll, Jennifer
Coutermarsh-Ott, Sheryl
Klahn, Shawna L.
Tuohy, Joanne L.
Barry, Sabrina L.
Allen, Irving C.
Hay, Alayna N.
Ruth, Jeffrey
Dervisis, Nikolaos G.
Dog
High-intensity focused ultrasound
immunotherapy
thermal ablation
Rare Diseases
Cancer
Purpose: To investigate the safety, feasibility, and outcomes of High-Intensity Focused Ultrasound (HIFU) for the treatment of solid tumors in a spontaneous canine cancer model.
Methods: Dogs diagnosed with subcutaneous solid tumors were recruited, staged and pretreatment biopsies were obtained. A single HIFU treatment was delivered to result in partial tumor ablation using a commercially available HIFU unit. Tumors were resected 3-6 days post HIFU and samples obtained for histopathology and immunohistochemistry. Total RNA was isolated from paired pre and post treated FFPE tumor samples, and quantitative gene expression analysis was performed using the nCounter Canine IO Panel.
Results: A total of 20 dogs diagnosed with solid tumors were recruited and treated in the study. Tumors treated included Soft Tissue Sarcoma (<i>n</i> = 15), Mast Cell Tumor (<i>n</i> = 3), Osteosarcoma (<i>n</i> = 1), and Thyroid Carcinoma (<i>n</i> = 1). HIFU was well tolerated with only 1 dog experiencing a clinically significant adverse event. Pathology confirmed the presence of complete tissue ablation at the HIFU targeted site and immunohistochemistry indicated immune cell infiltration at the treated/untreated tumor border. Quantitative gene expression analysis indicated that 28 genes associated with T-cell activation were differentially expressed post-HIFU.
Conclusions: HIFU appears to be safe and feasible for the treatment of subcutaneous canine solid tumors, resulting in ablation of the targeted tissue. HIFU induced immunostimulatory changes, highlighting the canine cancer patient as an attractive model for studying the effects of focal ablation therapies on the tumor microenvironment.
2022-08-02T19:53:53Z
2022-08-02T19:53:53Z
2022-08-02T19:53:53Z
2022-01
Article - Refereed
0265-6736
http://hdl.handle.net/10919/111429
https://doi.org/10.1080/02656736.2022.2097323
39
1
Dervisis, Nikolaos [0000-0003-2869-1483]
35848421
1464-5157
en
https://www.ncbi.nlm.nih.gov/pubmed/35848421
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Taylor & Francis
oai:vtechworks.lib.vt.edu:10919/849882023-04-14T17:49:46Zcom_10919_24259com_10919_5559col_10919_24342
A Systematic Review and Meta-Analysis of the Efficacy of Anti-Toxoplasma gondii Medicines in Humans
Wei, Hai-Xia
Wei, Shan-Shan
Lindsay, David S.
Peng, Hong-Juan
No effective drug and definitive “gold standard” treatment for Toxoplasma gondii (T. gondii) infection has been available so far, though some medicines have been commonly used in the treatment of T. gondii infection, such as spiramycin, azithromycin, traditional Chinese medicine (TCM), pyrimethamine- sulfadiazine (P-S), trimethoprim-sulfamethoxazole (TMP-SMX), and pyrimethamine-clindamycin (P-C). A systematic review and meta-analysis were performed to compare the efficacies of these conventional medicines in the treatment. Cohort studies for the treatment of acute T. gondii infection were searched from PubMed, Google Scholar, ect. All the cases number for different group extracted from each included literature were input to meta-analysis 3.13 software to calculate the pooled negative conversion rate (NCR), cure rate (CR) or vertical transmission rate based on their sample size and weight. The pooled NCR with 95% confidence intervals (CI) was used to evaluate the overall rate of a diagnosis positive result conversion to a negative result after treatment, which of spiramycin, azithromycin and TCM were 83.4% (95%CI, 72.1%-90.8%), 82.5% (95%CI, 75.9%-87.6%), and 85.5% (95%CI, 71.3%-93.3%) respectively, with no statistical difference between them. The pooled CR with 95% CI was used to evaluate the overall rate of complete disappearance of clinical symptoms for toxoplasmic encephalitis after therapy, which of P-S, TMP-SMX, and P-C were 49.8% (95%CI, 38. 8% -60.8%), 59.9% (95%CI, 48.9%-70.0%), and 47.6% (95%CI, 24.8%-71.4%) respectively, with no statistical difference between them. Primary T. gondii infection in pregnancy was treated mainly with spiramycin alone or combined with other drugs, and the pooled rate of vertical transmission was about 9.9% (95%CI, 5.9%-16.2%) after therapy. Toxoplasmic encephalitis in AIDS patients was usually treated with sulfonamides combined with other drugs and the pooled CR was 49.4% (95%CI, 37.9%-60.9%).
2018-09-10T18:52:21Z
2018-09-10T18:52:21Z
2018-09-10T18:52:21Z
2015-09-22
Article - Refereed
e0138204
http://hdl.handle.net/10919/84988
https://doi.org/10.1371/journal.pone.0138204
10
9
26394212
1932-6203
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
PLOS
oai:vtechworks.lib.vt.edu:10919/878042023-12-19T13:34:26Zcom_10919_24259com_10919_5559com_10919_72294col_10919_24342col_10919_23146col_10919_72295
Live attenuated chimeric porcine circovirus vaccine
Virginia Tech Intellectual Properties, Inc.
Meng, Xiang-Jin
Beach, Nathan M.
Ramamoorthy, Sheela
The present invention provides a novel chimeric porcine circovirus infectious DNA clone and live attenuated chimeric virus with the PCV2, preferably of subtype PCV2b, capsid gene integrated into a non-pathogenic PCV1 virus genome. In a particular embodiment, the PCV2 capids gene is of subtype PCV2b, the predominant subtype circulating in pigs worldwide. The attenuated chimeric virus, designated PCV1-2b, effectively protects pigs from PCV2b challenges, and can be used as a live vaccine, as well as an inactivated (killed) vaccine, that provides protection and cross protection against PCV2b and PCV2a subtypes infection. The live attenuated vaccine of the present invention is also effective protecting pigs from porcine circovirus-associated disease (PCVAD).
2019-02-26T22:23:54Z
2019-02-26T22:23:54Z
2019-02-26T22:23:54Z
2017-04-04
Patent
http://hdl.handle.net/10919/87804
http://pimg-fpiw.uspto.gov/fdd/44/103/096/0.pdf
14174635
9610344
en
United States Patent and Trademark Office
oai:vtechworks.lib.vt.edu:10919/1176882024-01-26T03:00:59Zcom_10919_23829com_10919_5553com_10919_24259com_10919_5559com_10919_25796com_10919_111086com_10919_5532com_10919_84995col_10919_23830col_10919_24342col_10919_25797col_10919_111087col_10919_84996
Phosphorylation of RPT6 Controls Its Ability to Bind DNA and Regulate Gene Expression in the Hippocampus of Male Rats during Memory Formation
Farrell, Kayla
Auerbach, Aubrey
Musaus, Madeline
Navabpour, Shaghayegh
Liu, Catherine
Lin, Yu
Xie, Hehuang
Jarome, Timothy J.
CRISPR
Hippocampus
memory
proteasome
RPT6
transcription
Memory formation requires coordinated control of gene expression, protein synthesis, and ubiquitin–proteasome system (UPS)-mediated protein degradation. The catalytic component of the UPS, the 26S proteasome, contains a 20S catalytic core surrounded by two 19S regulatory caps, and phosphorylation of the 19S cap regulatory subunit RPT6 at serine 120 (pRPT6-S120) has been widely implicated in controlling activity-dependent increases in proteasome activity. Recently, RPT6 was also shown to act outside the proteasome where it has a transcription factor-like role in the hippocampus during memory formation. However, little is known about the proteasome-independent function of “free” RPT6 in the brain or during memory formation and whether phosphorylation of S120 is required for this transcriptional control function. Here, we used RNA-sequencing along with novel genetic approaches and biochemical, molecular, and behavioral assays to test the hypothesis that pRPT6-S120 functions independently of the proteasome to bind DNA and regulate gene expression during memory formation. RNA-sequencing following siRNA-mediated knockdown of free RPT6 revealed 46 gene targets in the dorsal hippocampus of male rats following fear conditioning, where RPT6 was involved in transcriptional activation and repression. Through CRISPR-dCas9-mediated artificial placement of RPT6 at a target gene, we found that RPT6 DNA binding alone may be important for altering gene expression following learning. Further, CRISPR-dCas13-mediated conversion of S120 to glycine on RPT6 revealed that phosphorylation at S120 is necessary for RPT6 to bind DNA and properly regulate transcription during memory formation. Together, we reveal a novel function for phosphorylation of RPT6 in controlling gene transcription during memory formation.
2024-01-25T20:43:51Z
2024-01-25T20:43:51Z
2024-01-25T20:43:51Z
2024-01
Article - Refereed
https://hdl.handle.net/10919/117688
https://doi.org/10.1523/JNEUROSCI.1453-23.2023
44
4
en
Society for Neuroscience
oai:vtechworks.lib.vt.edu:10919/1074282022-04-15T20:52:16Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Theileria orientalis Ikeda Genotype in Cattle, Virginia, USA
Oakes, Vanessa J.
Yabsley, Michael J.
Schwartz, Diana
LeRoith, Tanya
Bissett, Carolynn
Broaddus, Charles
Schlater, Jack L.
Todd, S. Michelle
Boes, Katie M.
Brookhart, Meghan
Lahmers, Kevin K.
Life Sciences & Biomedicine
Immunology
Infectious Diseases
INFECTION
IXODIDAE
BUFFELI
Haemaphysalis longicornis
Ikeda genotype
Ixodidae
Theileria orientalis
United States
Virginia
anemia
cattle
infectious disease
parasites
theileriosis
tick-borne infections
ticks
vector-borne infections
zoonoses
Microbiology
1103 Clinical Sciences
1108 Medical Microbiology
1117 Public Health and Health Services
Theileria orientalis Ikeda genotype is a parasite that causes a disease in cattle that results in major economic issues in Asia, New Zealand, and Australia. The parasite is transmitted by Haemaphysalis longicornis ticks, which have recently been reported in numerous states throughout the eastern United States. Concurrently, cattle in Virginia showed clinical signs consistent with a hemoprotozoan infection. We used amplicons specific for the major piroplasm surface protein and small subunit rDNA of piroplasms to test blood samples from the cattle by PCR. Bidirectional Sanger sequencing showed sequences with 100% identity with T. orientalis Ikeda genotype 2 sequences. We detected the parasite in 3 unrelated herds and from various animals sampled at 2 time points. Although other benign T. orientalis genotypes are endemic to the United States, detection of T. orientalis Ikeda genotype might represent a risk for the cattle industry in Virginia.
2022-01-06T16:51:55Z
2022-01-06T16:51:55Z
2022-01-06T16:51:55Z
2019-09
Article - Refereed
1080-6040
http://hdl.handle.net/10919/107428
https://doi.org/10.3201/eid2509.190088
25
9
LeRoith, Tanya [0000-0002-1196-6949]
Lahmers, Kevin [0000-0002-5290-3426]
31237835
1080-6059
en
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000482626000005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1
https://www.ncbi.nlm.nih.gov/pubmed/31237835%20https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711211/pdf/19-0088.pdf
http://creativecommons.org/publicdomain/mark/1.0/
Public Domain
Centers for Disease Control and Prevention
oai:vtechworks.lib.vt.edu:10919/931902021-10-07T16:37:27Zcom_10919_24259com_10919_5559col_10919_24342
Hepatitis E Virus in Rabbits, Virginia, USA
Cossaboom, Caitlin M.
Cordoba, Laura
Dryman, Barbara A.
Meng, Xiang-Jin
genotype
swine
china
We identified hepatitis E virus (HEV) in rabbits in Virginia, USA. HEV RNA was detected in 14 (16%) of 85 serum samples and 13 (15%) of 85 fecal samples. Antibodies against HEV were detected in 31 (36%) of 85 serum samples. Sequence analyses showed that HEV from rabbits is closely related to genotype 3.
2019-08-20T12:42:11Z
2019-08-20T12:42:11Z
2019-08-20T12:42:11Z
2011-11
Article - Refereed
1080-6040
http://hdl.handle.net/10919/93190
https://doi.org/10.3201/eid1711.110428
17
11
22099094
1080-6059
en
http://creativecommons.org/publicdomain/zero/1.0/
Creative Commons CC0 1.0 Universal Public Domain Dedication
Virginia
United States
oai:vtechworks.lib.vt.edu:10919/1128922022-12-15T08:14:01Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Rampant prophage movement among transient competitors drives rapid adaptation during infection
Marshall, Christopher W.
Gloag, Erin S.
Lim, Christina
Wozniak, Daniel J.
Cooper, Vaughn S.
Biotechnology
Infectious Diseases
Genetics
2.1 Biological and endogenous factors
2 Aetiology
Infection
Interactions between bacteria, their close competitors, and viral parasites are common in infections, but understanding of these eco-evolutionary dynamics is limited. Most examples of adaptations caused by phage lysogeny are through the acquisition of new genes. However, integrated prophages can also insert into functional genes and impart a fitness benefit by disrupting their expression, a process called active lysogeny. Here, we show that active lysogeny can fuel rapid, parallel adaptations in establishing a chronic infection. These recombination events repeatedly disrupted genes encoding global regulators, leading to increased cyclic di-GMP levels and elevated biofilm production. The implications of prophage-mediated adaptation are broad, as even transient members of microbial communities can alter the course of evolution and generate persistent phenotypes associated with poor clinical outcomes.
2022-12-14T20:42:14Z
2022-12-14T20:42:14Z
2022-12-14T20:42:14Z
2021-07-16
Article - Refereed
2375-2548
PMC8284892
7/29/eabh1489 (PII)
http://hdl.handle.net/10919/112892
https://doi.org/10.1126/sciadv.abh1489
7
29
Gloag, Erin [0000-0001-8895-3444]
34272240
2375-2548
en
https://www.ncbi.nlm.nih.gov/pubmed/34272240
http://creativecommons.org/licenses/by-nc/4.0/
Creative Commons Attribution-NonCommercial 4.0 International
AAAS
oai:vtechworks.lib.vt.edu:10919/972332022-02-26T00:17:13Zcom_10919_24259com_10919_5559col_10919_24342
Re-Evaluation of Asynchronous Asexual Development of Cystoisospora canis in Intestines of Dogs
Dubey, Jitender P.
Lindsay, David S.
Cystoisospora canis (syn. Isospora canis)
Schizonts
Development
Generations
Asexual
Dog
Coccidian
Oocysts
Asynchronous
The coccidian parasite Cystoisospora canis (syn. Isospora canis) can cause clinical disease in dogs. Three generation of schizonts have been reported in the small intestine of dogs before oocysts are excreted 9-11 days post inoculation (PI). Here, we re-evaluated asexual development of C. canis in 2 dogs necropsied 10 days after oral inoculation with 100,000 C. canis oocysts; both dogs had excreted oocysts 9 days PI. Asexual and sexual stages were seen in the lamina propria throughout the small intestine. Merozoites of different sizes were present, often in the same vacuole. They were arranged singly, in pairs, and many within a single parasitophorous vacuole. The maximum number of nuclei within developing merozoites in a group was 8, but it could not be discerned if they were individual nuclei or parts of merozoites. Findings of abundant asexual stages 1 day after dogs had started excreting oocysts indicated continued asexual multiplication beyond the prepatent period. The stages found resemble the 3 generations reported previously. The mode of division of the asexual generations remains unclear. The results of the present study indicate that there are many generations that are difficult to determine because of the multiplication of merozoites in the original host cell without leaving it to enter new host cells. From the literature, it is evident that cat and dog coccidia (Cystoisospora spp.) divide by more than 1 type of division, including endodyogeny. In the past, the schizont/meront groups containing more than 1 generation have been called "cysts." However, cyst is not an accurate term because it is best used for an orally infective stage of coccidia; monozoic tissue cysts of C. canis can occur in paratenic hosts in extraintestinal organs. We recommend the term "types" as originally proposed for intestinal stages of Toxoplasma gondii and used for the original description of the life cycle of C. suis of swine when describing endogenous stages of the Sarcocystidae. Ultrastructural studies are needed to determine the precise form of multiplication of canine Cystoisospora species.
2020-03-06T17:57:00Z
2020-03-06T17:57:00Z
2020-03-06T17:57:00Z
2019-01-28
Article - Refereed
0022-3395
http://hdl.handle.net/10919/97233
https://doi.org/10.1645/18-131
105
1
30807723
1937-2345
en
http://creativecommons.org/publicdomain/zero/1.0/
Creative Commons CC0 1.0 Universal Public Domain Dedication
oai:vtechworks.lib.vt.edu:10919/894362020-10-13T19:02:46Zcom_10919_24259com_10919_5559col_10919_24342
A 6-Nucleotide Regulatory Motif within the AbcR Small RNAs of Brucella abortus Mediates Host-Pathogen Interactions
Sheehan, Lauren M.
Caswell, Clayton C.
In Brucella abortus, two small RNAs (sRNAs), AbcR1 and AbcR2, are responsible for regulating transcripts encoding ABC-type transport systems. AbcR1 and AbcR2 are required for Brucella virulence, as a double chromosomal deletion of both sRNAs results in attenuation in mice. Although these sRNAs are responsible for targeting transcripts for degradation, the mechanism utilized by the AbcR sRNAs to regulate mRNA in Brucella has not been described. Here, two motifs (M1 and M2) were identified in AbcR1 and AbcR2, and complementary motif sequences were defined in AbcR-regulated transcripts. Site-directed mutagenesis of M1 or M2 or of both M1 and M2 in the sRNAs revealed transcripts to be targeted by one or both motifs. Electrophoretic mobility shift assays revealed direct, concentration-dependent binding of both AbcR sRNAs to a target mRNA sequence. These experiments genetically and biochemically characterized two indispensable motifs within the AbcR sRNAs that bind to and regulate transcripts. Additionally, cellular and animal models of infection demonstrated that only M2 in the AbcR sRNAs is required for Brucella virulence. Furthermore, one of the M2-regulated targets, BAB2_0612, was found to be critical for the virulence of B. abortus in a mouse model of infection. Although these sRNAs are highly conserved among Alphaproteobacteria, the present report displays how gene regulation mediated by the AbcR sRNAs has diverged to meet the intricate regulatory requirements of each particular organism and its unique biological niche. IMPORTANCE Small RNAs (sRNAs) are important components of bacterial regulation, allowing organisms to quickly adapt to changes in their environments. The AbcR sRNAs are highly conserved throughout the Alphaproteobacteria and negatively regulate myriad transcripts, many encoding ABC-type transport systems. In Brucella abortus, AbcR1 and AbcR2 are functionally redundant, as only a double abcR1 abcR2 (abcR1/2) deletion results in attenuation in vitro and in vivo. In the present study, we confirmed that the AbcR sRNAs have redundant regulatory functions and defined two six-nucleotide motifs, M1 and M2, that the AbcR sRNAs utilize to control gene expression. Importantly, only M2 was linked to B. abortus virulence. Further investigation of M2-regulated targets identified BAB2_0612 as critical for colonization of B. abortus in mice, highlighting the significance of AbcR M2-regulated transcripts for Brucella infection. Overall, our findings define the molecular mechanism of the virulence-associated AbcR system in the pathogenic bacterium B. abortus.
2019-05-09T16:27:38Z
2019-05-09T16:27:38Z
2019-05-09T16:27:38Z
2017-05
Article - Refereed
Sheehan LM, Caswell CC. 2017. A 6-nucleotide regulatory motif within the AbcR small RNAs of Brucella abortus mediates host-pathogen interactions. mBio 8:e00473-17. https://doi.org/10.1128/mBio.00473-17.
2150-7511
e00473-17
http://hdl.handle.net/10919/89436
https://doi.org/10.1128/mBio.00473-17
8
3
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
American Society for Microbiology
oai:vtechworks.lib.vt.edu:10919/490622023-12-19T13:34:26Zcom_10919_24259com_10919_5559col_10919_24342
Oocyst excretion in dogs fed mouse brains containing tissue cysts of a cloned line of Neospora caninum
Lindsay, David S.
Ritter, D. M.
Brake, D.
abortion
seroprevalence
epidemic
cattle
cows
parasitology
Neospora caninum is an apicomplexan parasite that causes neonatal neuromuscular disease in dogs and abortions in cattle. Bovine neosporosis is a major production problem worldwide. The parasite is transmitted to cattle via oocysts excreted by dogs or by transplacental transmission. Dogs are the only proven definitive host for N. caninum. One of 3 dogs fed mouse brains containing tissue cysts of a wild-type N. caninum strain CK0160SC3B (CKO) excreted oocysts in its feces. Two of 3 dogs fed mouse brains containing tissue cysts from a cloned line of the CKO strain excreted N. caninum oocysts in their feces. The results indicate that a single N. caninum tachyzoite contains all the genetic information needed to produce the asexual and sexual cycles in the canine intestine.
2014-06-20T14:13:18Z
2014-06-20T14:13:18Z
2014-06-20T14:13:18Z
2001-08
Article - Refereed
David S. Lindsay, Dianne M. Ritter, and David Brake (2001). "Oocyst Excretion in Dogs Fed Mouse Brains Containing Tissue Cysts of a Cloned Line of Neospora Caninum," Journal of Parasitology, Vol. 87, No. 4, pp. 909-911. doi: http://dx.doi.org/10.1645/0022-3395(2001)087[0909:OEIDFM]2.0.CO;2
0022-3395
http://hdl.handle.net/10919/49062
http://www.bioone.org/doi/abs/10.1645/0022-3395%282001%29087%5B0909%3AOEIDFM%5D2.0.CO%3B2
https://doi.org/10.1645/0022-3395(2001)087[0909:oeidfm]2.0.co;2
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/952112020-10-15T20:33:37Zcom_10919_78629com_10919_78628com_10919_24259com_10919_5559col_10919_78791col_10919_24342
Potential of Stem Cell-Based Therapy for Ischemic Stroke
Marei, Hany E.
Hasan, A.
Rizzi, R.
Althani, A.
Afifi, N.
Cenciarelli, C.
Caceci, Thomas
Shuaib, Ashfaq
stem cell
mesenchymal stem cell
neural stem cell
induced pluripotent stem cells
ischemic stroke
Ischemic stroke is one of the major health problems worldwide. The only FDA approved anti-thrombotic drug for acute ischemic stroke is the tissue plasminogen activator. Several studies have been devoted to assessing the therapeutic potential of different types of stem cells such as neural stem cells (NSCs), mesenchymal stem cells, embryonic stem cells, and human induced pluripotent stem cell-derived NSCs as treatments for ischemic stroke. The results of these studies are intriguing but many of them have presented conflicting results. Additionally, the mechanism(s) by which engrafted stem/progenitor cells exert their actions are to a large extent unknown. In this review, we will provide a synopsis of different preclinical and clinical studies related to the use of stem cell-based stroke therapy, and explore possible beneficial/detrimental outcomes associated with the use of different types of stem cells. Due to limited/short time window implemented in most of the recorded clinical trials about the use of stem cells as potential therapeutic intervention for stroke, further clinical trials evaluating the efficacy of the intervention in a longer time window after cellular engraftments are still needed.
2019-10-30T13:05:07Z
2019-10-30T13:05:07Z
2019-10-30T13:05:07Z
2018-02-06
Article - Refereed
1664-2295
34
http://hdl.handle.net/10919/95211
https://doi.org/10.3389/fneur.2018.00034
9
29467713
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Frontiers
oai:vtechworks.lib.vt.edu:10919/1000262023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Repurposing celecoxib as a topical antimicrobial agent
Thangamani, Shankar
Younis, Waleed
Seleem, Mohamed N.
Microbiology
celecoxib
antimicrobial resistance
repurposing
skin infection
anti-inflammatory
RESISTANT STAPHYLOCOCCUS-AUREUS
COMMUNITY-ASSOCIATED STRAINS
FUSIDIC ACID RESISTANCE
CYCLOOXYGENASE-2 INHIBITOR
PSEUDOMONAS-AERUGINOSA
ESCHERICHIA-COLI
INFLAMMATION
INFECTIONS
EPIDEMIOLOGY
ARTHRITIS
0502 Environmental Science and Management
0503 Soil Sciences
0605 Microbiology
There is an urgent need for new antibiotics and alternative strategies to combat multidrug-resistant bacterial pathogens, which are a growing clinical issue. Repurposing existing approved drugs with known pharmacology and toxicology is an alternative strategy to accelerate antimicrobial research and development. In this study, we show that celecoxib, a marketed inhibitor of cyclooxygenase-2, exhibits broad-spectrum antimicrobial activity against Gram-positive pathogens from a variety of genera, including Staphylococcus, Streptococcus, Listeria, Bacillus, and Mycobacterium, but not against Gram-negative pathogens. However, celecoxib is active against all of the Gram-negative bacteria tested, including strains of, Acinetobacter, and Pseudomonas, when their intrinsic resistance is artificially compromised by outer membrane permeabilizing agents such as colistin. The effect of celecoxib on incorporation of radioactive precursors into macromolecules in Staphylococcus aureus was examined. The primary antimicrobial mechanism of action of celecoxib was the dose-dependent inhibition of RNA, DNA, and protein synthesis. Further, we demonstrate the in vivo efficacy of celecoxib in a methicillin-resistant S. aureus (MRSA) infected Caenorhabditis elegans whole animal model. Topical application of celecoxib (1 and 2%) significantly reduced the mean bacterial count in a mouse model of MRSA skin infection. Further, celecoxib decreased the levels of all inflammatory cytokines tested, including tumor necrosis factor-a, interleukin-6, interleukin-1 beta, and monocyte chemo attractant protein-1 in wounds caused by MRSA infection. Celecoxib also exhibited synergy with many conventional antimicrobials when tested against four clinical isolates of S. aureus. Collectively, these results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections.
2020-09-21T16:12:25Z
2020-09-21T16:12:25Z
2020-09-21T16:12:25Z
2015-07-28
Article - Refereed
1664-302X
http://hdl.handle.net/10919/100026
https://doi.org/10.3389/fmicb.2015.00750
6
JUL
Seleem, Mohamed [0000-0003-0939-0458]
26284040 (pubmed)
1664-302X
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Frontiers
oai:vtechworks.lib.vt.edu:10919/490502023-12-19T13:34:26Zcom_10919_24259com_10919_5559col_10919_24342
The gamma interferon knockout mouse model for Sarcocystis neurona: Comparison of infectivity of sporocysts and merozoites and routes of inoculation
Dubey, Jitender P.
Lindsay, David S.
Kwok, O. C. H.
Shen, S. K.
equine protozoal myeloencephalitis
opossum didelphis-virginiana
n-sp
protozoa
falcatula
mice
parasitology
The dose-related infectivity of Sarcocystis neurona sporocysts and merozoites. of 2 recent isolates of S. neurona was compared in gamma interferon knockout (KO) mice. Tenfold dilutions of sporocysts or merozoites were bioassayed in mice, cell culture, or both. All 8 mice, fed 1,000 sporocysts, developed neurological signs with demonstrable S. neurona in their tissues. Of 24 mice fed low numbers of sporocysts. (100, 10, 1), 18 became ill by 4 wk postinoculation, and S. neurona was demonstrated in their brains; antibodies (S. neurona agglutination test) to S. neurona and S. neurona parasites were not found in tissues of the 6 mice that were fed sporocysts and survived for >39 days. One thousand culture-derived merozoites of these 2 isolates were pathogenic to all 8 mice inoculated subcutaneously (s.c.). Of the 24 mice inoculated s.c. with merozoites. numbering 100, 10, or 1, only 3 mice had demonstrable S. neurona infection; antibodies to S. neurona were not found in the 21 mice that had no demonstrable organisms. As few as 10 merozoites. were infective for cell cultures. These results demonstrate that at least 1,000 merozoites are needed to cause disease in KO mice. Sarcocystis neurona sporocysts were infective to mice by the s.c. route.
2014-06-20T14:13:14Z
2014-06-20T14:13:14Z
2014-06-20T14:13:14Z
2001-10
Article - Refereed
J. P. Dubey, D. S. Lindsay, O. C H. Kwok, and S. K. Shen (2001). "The Gamma Interferon Knockout Mouse Model for Sarcocystis neurona: Comparison of Infectivity of Sporocysts and Merozoites and Routes of Inoculation," Journal of Parasitology, Vol. 87, No. 5, pp. 1171-1173. doi: http://dx.doi.org/10.1645/0022-3395(2001)087[1171:TGIKMM]2.0.CO;2
0022-3395
http://hdl.handle.net/10919/49050
http://www.bioone.org/doi/abs/10.1645/0022-3395%282001%29087%5B1171%3ATGIKMM%5D2.0.CO%3B2
https://doi.org/10.1645/0022-3395(2001)087[1171:tgikmm]2.0.co;2
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/1107502023-11-29T11:19:56Zcom_10919_78629com_10919_78628com_10919_8195com_10919_25799com_10919_24259com_10919_5559com_10919_103712com_10919_25796col_10919_78630col_10919_18629col_10919_24342col_10919_103713
Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
Nyblade, Charlotte
Parreno, Viviana
Zhou, Peng
Hensley, Casey
Oakes, Vanessa
Mahsoub, Hassan M.
Kiley, Kelsey
Frazier, Maggie
Frazier, Annie
Zhang, Yongrong
Feng, Hanping
Yuan, Lijuan
Clostridioides difficile (C. difficile) is a gram-positive, spore-forming, anaerobic bacterium known to be the most common cause of hospital-acquired and antibiotic-associated diarrhea. C. difficile infection rates are on the rise worldwide and treatment options are limited, indicating a clear need for novel therapeutics. Gnotobiotic piglets are an excellent model to reproduce the acute pseudomembranous colitis (PMC) caused by C. difficile due to their physiological similarities to humans and high susceptibility to infection. Here, we established a gnotobiotic pig model of C. difficile infection and disease using a hypervirulent strain. C. difficile-infected pigs displayed classic signs of C. difficile infection, including severe diarrhea and weight loss. Inoculated pigs had severe gross and microscopic intestinal lesions. C. difficile infection caused an increase in pro-inflammatory cytokines in samples of serum, large intestinal contents, and pleural effusion. C. difficile spores and toxins were detected in the feces of inoculated animals as tested by anaerobic culture and cytotoxicity assays. Successful establishment of this model is key for future work as therapeutics can be evaluated in an environment that accurately mimics what happens in humans. The model is especially suitable for evaluating potential prophylactics and therapeutics, including vaccines and passive immune strategies.
2022-06-13T11:38:20Z
2022-06-13T11:38:20Z
2022-06-13T11:38:20Z
2022-06-06
Article - Refereed
Gut Pathogens. 2022 Jun 06;14(1):22
http://hdl.handle.net/10919/110750
https://doi.org/10.1186/s13099-022-00496-y
en
http://creativecommons.org/licenses/by/4.0/
The Author(s)
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/1158152023-07-22T07:12:35Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
European Haplotype of <i>Echinococcus multilocularis</i> in the United States
Polish, Louis B.
O'Connell, Elise M.
Barth, Thomas F. E.
Gottstein, Bruno
Zajac, Anne M.
Gibson, Pamela C.
Bah, Aissatou
Kirchgessner, Megan
Estrada, Marko
Seguin, M. Alexis
Ramirez-Barrios, Roger
2023-07-21T19:28:49Z
2023-07-21T19:28:49Z
2023-07-21T19:28:49Z
2022-11
Article - Refereed
0028-4793
PMC10072850
http://hdl.handle.net/10919/115815
https://doi.org/10.1056/nejmc2210000
387
20
Ramirez Barrios, Roger [0000-0002-4724-6724]
36383717
1533-4406
en
https://www.ncbi.nlm.nih.gov/pubmed/36383717
http://creativecommons.org/publicdomain/mark/1.0/
Public Domain (U. S.)
Massachusetts Medical Society
oai:vtechworks.lib.vt.edu:10919/1125542022-11-11T08:15:02Zcom_10919_24259com_10919_5559col_10919_24342
Human Milk Oligosaccharides Impact Cellular and Inflammatory Gene Expression and Immune Response
Rosa, Fernanda
Sharma, Ashok K.
Gurung, Manoj
Casero, David
Matazel, Katelin
Bode, Lars
Simecka, Christy
Elolimy, Ahmed A.
Tripp, Patricia
Randolph, Christopher
Hand, Timothy W.
Williams, Keith D.
LeRoith, Tanya
Yeruva, Laxmi
human milk oligosaccharides
HMO
immunity
gastrointestinal tract
neonatal
Human milk harbors complex carbohydrates, including human milk oligosaccharides (HMOs), the third most abundant component after lactose and lipids. HMOs have been shown to impact intestinal microbiota, modulate the intestinal immune response, and prevent pathogenic bacterial binding by serving as decoy receptors. However, the direct effect of HMOs on intestinal function and immunity remains to be elucidated. To address this knowledge gap, 21-day-old germ-free mice (C57BI/6) were orally gavaged with 15 mg/day of pooled HMOs for 7 or 14 days and euthanized at day 28 or 35. A set of mice was maintained until day 50 to determine the persistent effects of HMOs. Control groups were maintained in the isolators for 28, 35, or 50 days of age. At the respective endpoints, intestinal tissues were subjected to histomorphometric and transcriptomic analyses, while the spleen and mesenteric lymph nodes (MLNs) were subjected to flow cytometric analysis. The small intestine (SI) crypt was reduced after HMO treatment relative to control at days 28 and 35, while the SI villus height and large intestine (LI) gland depth were decreased in the HMO-treated mice relative to the control at day 35. We report significant HMO-induced and location-specific gene expression changes in host intestinal tissues. HMO treatment significantly upregulated genes involved in extracellular matrix, protein ubiquitination, nuclear transport, and mononuclear cell differentiation. CD4+ T cells were increased in both MLNs and the spleen, while CD8+ T cells were increased in the spleen at day 50 in the HMO group in comparison to controls. In MLNs, plasma cells were increased in HMO group at days 28 and 35, while in the spleen, only at day 28 relative to controls. Macrophages/monocytes and neutrophils were lower in the spleen of the HMO group at days 28, 35, and 50, while in MLNs, only neutrophils were lower at day 50 in the 14-day HMO group. In addition, diphtheria toxoid and tetanus toxoid antibody-secreting cells were higher in HMO-supplemented group compared to controls. Our data suggest that HMOs have a direct effect on gastrointestinal tract metabolism and the immune system even in the absence of host microbiota.
2022-11-10T15:05:59Z
2022-11-10T15:05:59Z
2022-11-10T15:05:59Z
2022-06-29
Article - Refereed
1664-3224
907529
http://hdl.handle.net/10919/112554
https://doi.org/10.3389/fimmu.2022.907529
13
35844612
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Frontiers
oai:vtechworks.lib.vt.edu:10919/1116222023-11-29T11:19:57Zcom_10919_24259com_10919_5559com_10919_103712com_10919_25796col_10919_24342col_10919_103713
Dithiocarbamates effectively inhibit the alpha-carbonic anhydrase from Neisseria gonorrhoeae
Giovannuzzi, Simone
Abutaleb, Nader S.
Hewitt, Chad S.
Carta, Fabrizio
Nocentini, Alessio
Seleem, Mohamed N.
Flaherty, Daniel P.
Supuran, Claudiu T.
Carbonic anhydrase
inhibitor
dithiocarbamate
Neisseria gonorrhoeae
antibacterials
Recently, inorganic anions and sulphonamides, two of the main classes of zinc-binding carbonic anhydrase inhibitors (CAIs), were investigated for inhibition of the alpha-class carbonic anhydrase (CA, EC 4.2.1.1) from Neisseria gonorrhoeae, NgCA. As an extension to our previous studies, we report that dithiocarbamates (DTCs) derived from primary or secondary amines constitute a class of efficient inhibitors of NgCA. K(I)s ranging between 83.7 and 827 nM were measured for a series of 31 DTCs that incorporated various aliphatic, aromatic, and heterocyclic scaffolds. A subset of DTCs were selected for antimicrobial testing against N. gonorrhoeae, and three molecules displayed minimum inhibitory concentration (MIC) values less than or equal to 8 mu g/mL. As NgCA was recently validated as an antibacterial drug target, the DTCs may lead to development of novel antigonococcal agents.
2022-08-24T17:13:04Z
2022-08-24T17:13:04Z
2022-08-24T17:13:04Z
2022-01-01
Article - Refereed
1475-6366
http://hdl.handle.net/10919/111622
https://doi.org/10.1080/14756366.2021.1988945
37
1
34894954
1475-6374
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Taylor & Francis
oai:vtechworks.lib.vt.edu:10919/790582021-09-23T19:43:45Zcom_10919_8195com_10919_25799com_10919_24259com_10919_5559com_10919_23274com_10919_5539col_10919_78797col_10919_24342col_10919_23275col_10919_23146
In Situ Real-Time Chemiluminescence Imaging of Reactive Oxygen Species Formation from Cardiomyocytes
Li, Yunbo
Shen, Haiou
Zhu, Hong
Trush, Michael A.
Jiang, Ming
Wang, Ge
Biomedical Sciences and Pathobiology
School of Biomedical Engineering and Sciences
Virginia-Maryland College of Veterinary Medicine
We have applied the highly sensitive chemiluminescence (CL) imagingtechnique to investigate the in situ ROS formation in cultured monolayers of rat H9c2 cardiomyocytes. Photon emission was detected via an innovative imaging system after incubation of H9c2 cells in culture with luminol and horseradish peroxidase (HRP), suggesting constitutive formation of ROS by the cardiomyocytes. Addition of benzo(a)pyrene-1,6-quinone(BPQ) to cultured H9c2 cells resulted in a 4-5-fold increase in the formation of ROS, as detected by the CL imaging. Both constitutive and BPQ-stimulated CL responses in cultured H9c2 cells were sustained for up to 1 hour. The CL responses were completely abolished in the presence of superoxide dismutase and catalase, suggesting the primary involvement of superoxide and hydrogen peroxide (). In contrast to BPQ-mediated redox cycling, blockage of mitochondrial electron transport chain by either antimycin A or rotenone exerted marginal effects on the ROS formation by cultured H9c2 cells. Upregulation of cellular antioxidants fordetoxifying both superoxide and by 3-1,2-dithiole-3-thione resulted in marked inhibition of both constitutive and BPQ-augmented ROS formation in cultured H9c2 cells. Taken together, we demonstrate the sensitive detection of ROS by CL imaging in cultured cardiomyocytes.
2017-09-18T10:02:39Z
2017-09-18T10:02:39Z
2017-09-18T10:02:39Z
2009-02-25
Article - Refereed
Yunbo Li, Haiou Shen, Hong Zhu, Michael A. Trush, Ming Jiang, and Ge Wang, “In Situ Real-Time Chemiluminescence Imaging of Reactive Oxygen Species Formation from Cardiomyocytes,” International Journal of Biomedical Imaging, vol. 2008, Article ID 941729, 9 pages, 2008. doi:10.1155/2008/941729
http://hdl.handle.net/10919/79058
https://doi.org/10.1155/2008/941729
en
http://creativecommons.org/licenses/by/4.0/
Copyright © 2008 Yunbo Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution 4.0 International
Hindawi
oai:vtechworks.lib.vt.edu:10919/1052792023-11-29T11:24:57Zcom_10919_78629com_10919_78628com_10919_8195com_10919_25799com_10919_24259com_10919_5559com_10919_103712com_10919_25796com_10919_24230com_10919_5532col_10919_78630col_10919_78882col_10919_24342col_10919_103713col_10919_24305col_10919_25797col_10919_23146
Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine
Porier, Danielle L.
Wilson, Sarah N.
Auguste, Dawn I.
Leber, Andrew
Coutermarsh-Ott, Sheryl
Allen, Irving C.
Caswell, Clayton C.
Budnick, James A.
Bassaganya-Riera, Josep
Hontecillas, Raquel
Weger-Lucarelli, James
Weaver, Scott C.
Auguste, Albert J.
Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV). ZIKV has caused immense economic and public health impacts throughout the Americas and remains a significant public health threat. ARPV/ZIKV vaccination showed exceptional safety due to ARPV/ZIKV’s inherent vertebrate host-restriction. ARPV/ZIKV showed no evidence of replication or translation <i>in vitro</i> and showed no hematological, histological or pathogenic effects <i>in vivo</i>. A single-dose immunization with ARPV/ZIKV induced rapid and robust neutralizing antibody and cellular responses, which offered complete protection against ZIKV-induced morbidity, mortality and in utero transmission in immune-competent and -compromised murine models. Splenocytes derived from vaccinated mice demonstrated significant CD4<sup>+</sup> and CD8<sup>+</sup> responses and significant cytokine production post-antigen exposure. Altogether, our results further support that chimeric insect-specific flaviviruses are a promising strategy to restrict flavivirus emergence via vaccine development.
2021-10-13T12:29:18Z
2021-10-13T12:29:18Z
2021-10-13T12:29:18Z
2021-10-07
Article - Refereed
Porier, D.L.; Wilson, S.N.; Auguste, D.I.; Leber, A.; Coutermarsh-Ott, S.; Allen, I.C.; Caswell, C.C.; Budnick, J.A.; Bassaganya-Riera, J.; Hontecillas, R.; Weger-Lucarelli, J.; Weaver, S.C.; Auguste, A.J. Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine. Vaccines 2021, 9, 1142.
http://hdl.handle.net/10919/105279
https://doi.org/10.3390/vaccines9101142
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/490842023-12-19T13:34:26Zcom_10919_24259com_10919_5559col_10919_24342
Sarcocysts of an unidentified species of Sarcocystis in the sea otter (Enhydra lutris)
Dubey, Jitender P.
Lindsay, David S.
Rosenthal, B. M.
Thomas, N. J.
south-american opossum
didelphis-albiventris
neurona
brazil
infection
nereis
parasitology
The number of Sarcocystis species that infect sea otters (Enhydra lutris) is unknown. Sea otter tissues were recently shown to harbor sarcocysts of S. neurona and of unidentified species of Sarcocystis. Whereas sarcocysts of S. neurona have walls 1-3 mum thick with type 9 villar protrusions, ultrastructure of a distinct thin-walled sarcocyst (0.5-0.7 mum thick) lacking villar protrusions, but instead exhibiting minute type I undulations on the sarcocyst wall, is described in this report. Parasites characterized from a sea otter infection were inferred to be related to, but distinct from, other species belonging to Sarcocystis, based on sequencing and phylogenetic analysis of a portion of the beta subunit of the plastid-encoded RNA polymerase gene.
2014-06-20T14:13:22Z
2014-06-20T14:13:22Z
2014-06-20T14:13:22Z
2003-04
Article - Refereed
J. P. Dubey, D. S. Lindsay, B. M. Rosenthal, and N. J. Thomas (2003). "Sarcocysts of an Unidentified Species of Sarcocystis in the Sea Otter (Enhydra lutris)," Journal of Parasitology, Vol. 89, No. 2, pp. 397-399. doi: http://dx.doi.org/10.1645/0022-3395(2003)089[0397:SOAUSO]2.0.CO;2
0022-3395
http://hdl.handle.net/10919/49084
http://www.bioone.org/doi/abs/10.1645/0022-3395%282003%29089%5B0397%3ASOAUSO%5D2.0.CO%3B2
https://doi.org/10.1645/0022-3395(2003)089[0397:soauso]2.0.co;2
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/1127032023-11-29T11:25:01Zcom_10919_8195com_10919_25799com_10919_23829com_10919_5553com_10919_24259com_10919_5559com_10919_91913com_10919_23198com_10919_25796com_10919_91912col_10919_18629col_10919_23830col_10919_24342col_10919_91914col_10919_25797col_10919_91916
Folate regulates RNA m5C modification and translation in neural stem cells
Xu, Xiguang
Johnson, Zachary
Wang, Amanda
Padget, Rachel L.
Smyth, James W.
Xie, Hehuang
Background
Folate is an essential B-group vitamin and a key methyl donor with important biological functions including DNA methylation regulation. Normal neurodevelopment and physiology are sensitive to the cellular folate levels. Either deficiency or excess of folate may lead to neurological disorders. Recently, folate has been linked to tRNA cytosine-5 methylation (m5C) and translation in mammalian mitochondria. However, the influence of folate intake on neuronal mRNA m5C modification and translation remains largely unknown. Here, we provide transcriptome-wide landscapes of m5C modification in poly(A)-enriched RNAs together with mRNA transcription and translation profiles for mouse neural stem cells (NSCs) cultured in three different concentrations of folate.
Results
NSCs cultured in three different concentrations of folate showed distinct mRNA methylation profiles. Despite uncovering only a few differentially expressed genes, hundreds of differentially translated genes were identified in NSCs with folate deficiency or supplementation. The differentially translated genes induced by low folate are associated with cytoplasmic translation and mitochondrial function, while the differentially translated genes induced by high folate are associated with increased neural stem cell proliferation. Interestingly, compared to total mRNAs, polysome mRNAs contained high levels of m5C. Furthermore, an integrative analysis indicated a transcript-specific relationship between RNA m5C methylation and mRNA translation efficiency.
Conclusions
Altogether, our study reports a transcriptome-wide influence of folate on mRNA m5C methylation and translation in NSCs and reveals a potential link between mRNA m5C methylation and mRNA translation.
2022-11-28T13:46:23Z
2022-11-28T13:46:23Z
2022-11-28T13:46:23Z
2022-11-23
Article - Refereed
BMC Biology. 2022 Nov 23;20(1):261
http://hdl.handle.net/10919/112703
https://doi.org/10.1186/s12915-022-01467-0
en
http://creativecommons.org/licenses/by/4.0/
The Author(s)
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/1049352021-09-08T07:11:08Zcom_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_18629col_10919_24342
Retrospective study of canine endoparasites diagnosed by fecal flotation methods analyzed across veterinary parasitology diagnostic laboratories, United States, 2018
Sobotyk, Caroline
Upton, Kaitlyn E.
Lejeune, Manigandan
Nolan, Thomas J.
Marsh, Antoinette E.
Herrin, Brian H.
Borst, Mindy M.
Piccione, Julie
Zajac, Anne M.
Camp, Lauren E.
Pulaski, Cassan N.
Starkey, Lindsay A.
von Simson, Cristiano
Verocai, Guilherme G.
Biomedical Sciences and Pathobiology
Background
Companion animal endoparasites play a substantial role in both veterinary medicine and public health. Updated epidemiological studies are necessary to identify trends in occurrence and distribution of these parasites, and their associated risk factors. This study aimed to assess the occurrence of canine endoparasites retrospectively, using fecal flotation test data available through participating academic veterinary parasitology diagnostic laboratories across the United States of America (USA).
Methods
Canine fecal flotation records from ten veterinary diagnostic laboratories located in nine states in the USA acquired from January 1, 2018, to December 31, 2018, were included.
Results
A total of 4692 fecal flotation test results were obtained, with a majority comprised of client-owned dogs (3262; 69.52%), followed by research dogs (375; 8.00%), and shelter dogs (122; 2.60%). Samples from 976 (20.80%) dogs were positive for at least one parasite, and co-infections of two or more parasites were found in 3.82% (179/4692) of the samples. The five most commonly detected parasites were: Giardia sp., (8.33%; 391/4692), Ancylostomatidae (5.63%; 264/4692), Cystoisospora spp. (4.35%; 204/4692), Toxocara canis (2.49%;117/4692), and Trichuris vulpis (2.43%; 114/4692). Various other internal parasites, including gastrointestinal and respiratory nematodes, cestodes, trematodes, and protozoans were detected in less than 1% of samples.
Conclusions
These data illustrate the importance of parasite prevention, routine fecal screening, and treatment of pet dogs. Additionally, pet owners should be educated about general parasite prevalence, prevention, and anthelmintic treatment regimens to reduce the risks of environmental contamination and zoonotic transmission.
2021-09-07T11:49:29Z
2021-09-07T11:49:29Z
2021-09-07T11:49:29Z
2021-08-31
Article - Refereed
Parasites & Vectors. 2021 Aug 31;14(1):439
http://hdl.handle.net/10919/104935
https://doi.org/10.1186/s13071-021-04960-7
en
http://creativecommons.org/licenses/by/4.0/
The Author(s)
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/490392023-12-19T13:34:26Zcom_10919_24259com_10919_5559col_10919_24342
Effects of Age and Breed on the Prevalence of Neospora caninum in Commercial Dairy Cattle from Pakistan
Nazir, M. M.
Maqbool, A.
Khan, M. S.
Sajjid, A.
Lindsay, David S.
dogs
infection
seroprevalence
transmission
oocysts
herds
epidemiology
antibodies
disease
state
parasitology
Neospora caninum is a major cause of bovine abortion worldwide. A serological survey was carried out to determine the seroprevalence of exposure to N. caninum in dairy cattle based on age and breed from Punjab and Sindh provinces, Pakistan. Serum samples from 641 animals from 12 herds from Punjab (n = 7) and Sindh (n = 5) provinces were tested for antibodies against N. caninum using a commercially available competitive enzyme-linked immunosorbent assay. Positive reactions to N. caninum were seen in 277 (43%) of the 641 of the samples. Seropositive animals were present in all 12 herds. Animals over 2 yr of age (47%) and crossbreds (55%) were more likely to be seropositive than the other cattle examined. These results indicate that N. caninum infection is widespread among dairy cattle in Pakistan.
2014-06-20T14:13:12Z
2014-06-20T14:13:12Z
2014-06-20T14:13:12Z
2013-04
Article - Refereed
Muhammad Mudasser Nazir, Azhar Maqbool, Muhammad Sarwar Khan, Afzal Sajjid, and David S. Lindsay (2013). "Effects of Age and Breed on the Prevalence of Neospora caninum in Commercial Dairy Cattle from Pakistan," Journal of Parasitology, Vol. 99, No. 2, pp. 368-370. doi: http://dx.doi.org/10.1645/GE-3173.1
0022-3395
http://hdl.handle.net/10919/49039
http://www.bioone.org/doi/abs/10.1645/GE-3173.1
https://doi.org/10.1645/ge-3173.1
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/1051052023-06-21T19:15:06Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559com_10919_19035com_10919_5539com_10919_18738col_10919_70873col_10919_24342col_10919_24290col_10919_23145
Identifying multi-hit carcinogenic gene combinations: Scaling up a weighted set cover algorithm using compressed binary matrix representation on a GPU
Al Hajri, Qais
Dash, Sajal
Feng, Wu-chun
Garner, Harold R.
Anandakrishnan, Ramu
Electrical and Computer Engineering
Computer Science
Biomedical Sciences and Pathobiology
cancer driver genes
somatic mutations
breast-cancer
p53
ovarian
tp53
instability
expression
mutants
gain
Despite decades of research, effective treatments for most cancers remain elusive. One reason is that different instances of cancer result from different combinations of multiple genetic mutations (hits). Therefore, treatments that may be effective in some cases are not effective in others. We previously developed an algorithm for identifying combinations of carcinogenic genes with mutations (multi-hit combinations), which could suggest a likely cause for individual instances of cancer. Most cancers are estimated to require three or more hits. However, the computational complexity of the algorithm scales exponentially with the number of hits, making it impractical for identifying combinations of more than two hits. To identify combinations of greater than two hits, we used a compressed binary matrix representation, and optimized the algorithm for parallel execution on an NVIDIA V100 graphics processing unit (GPU). With these enhancements, the optimized GPU implementation was on average an estimated 12,144 times faster than the original integer matrix based CPU implementation, for the 3-hit algorithm, allowing us to identify 3-hit combinations. The 3-hit combinations identified using a training set were able to differentiate between tumor and normal samples in a separate test set with 90% overall sensitivity and 93% overall specificity. We illustrate how the distribution of mutations in tumor and normal samples in the multi-hit gene combinations can suggest potential driver mutations for further investigation. With experimental validation, these combinations may provide insight into the etiology of cancer and a rational basis for targeted combination therapy.
2021-09-29T16:23:30Z
2021-09-29T16:23:30Z
2021-09-29T16:23:30Z
2020-02-06
Article - Refereed
2045-2322
10.1038/s41598-020-58785-y (PII)
http://hdl.handle.net/10919/105105
https://doi.org/10.1038/s41598-020-58785-y
10
1
32029803
2045-2322
en
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000559759500020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Nature Publishing Group
oai:vtechworks.lib.vt.edu:10919/1046162022-03-29T14:34:44Zcom_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_78882col_10919_24342
Phloretin Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Regulating the Inflammatory Response, Oxidative Stress and Apoptosis
Hsu, Chao Yu
Lin, Yi Sheng
Weng, Wei Chun
Panny, Lauren
Chen, Hsiang Lai
Tung, Min Che
Ou, Yen Chuan
Lin, Chi-Chien
Yang, Che Hsueh
Biomedical Sciences and Pathobiology
prostatic hyperplasia
phloretin
anti-inflammatory
antioxidants
Apoptosis
The inflammatory process is proposed to be one of the factors to benign prostatic enlargement (BPH), and this is the first study examining the anti-inflammatory ability of phloretin in treating rats with testosterone-induced BPH. BPH would be induced by testosterone (10 mg/kg/day testosterone subcutaneously for 28 days), and the other groups of rats were treated with phloretin 50 mg/kg/day or 100 mg/kg/day orally (phr50 or phr100 group) after induction. Prostate weight and prostate weight to body weight ratio were significantly reduced in the Phr100 group. Reduced dihydrotestosterone without interfering with 5α-reductase was observed in the phr100 group. In inflammatory proteins, reduced IL-6, IL-8, IL-17, NF-κB, and COX-2 were seen in the phr100 group. In reactive oxygen species, malondialdehyde was reduced, and superoxide dismutase and glutathione peroxidase were elevated in the phr100 group. In apoptotic assessment, elevated cleaved caspase-3 was observed in rats of the phr100 group. Enhanced pro-apoptotic Bax and reduced anti-apoptotic Bc1-2 could be seen in the phr100 group. In histological stains, markedly decreased glandular hyperplasia and proliferative cell nuclear antigen were observed with reduced expression in the phr100 group. Meanwhile, positive cells of terminal deoxynucleotidyl transferase dUTP nick end labeling were increased in the phr100 group. In conclusion, the treatment of phloretin 100 mg/kg/day could ameliorate testosterone-induced BPH.
2021-08-09T16:55:41Z
2021-08-09T16:55:41Z
2021-08-09T16:55:41Z
2021-07-26
Article - Refereed
Hsu, C.Y.; Lin, Y.S.; Weng, W.C.; Panny, L.; Chen, H.L.; Tung, M.C.; Ou, Y.C.; Lin, C.C.; Yang, C.H. Phloretin Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Regulating the Inflammatory Response, Oxidative Stress and Apoptosis. Life 2021, 11, 743.
http://hdl.handle.net/10919/104616
https://doi.org/10.3390/life11080743
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/1026192021-03-06T08:18:29Zcom_10919_24259com_10919_5559com_10919_111086com_10919_5532col_10919_24342col_10919_111087
Differentiating Vaccine-Related Fowl Cholera from Naturally Occurring Disease
Hutcheson, Anna R.
Thompson, Kasey
Maurer, John J.
Ferguson, Naola
Grogan, Karen
Roney, Stephen
Seahorn, Harmony
Lobsinger, Chris
Lee, Margie D.
Biomedical Sciences and Pathobiology
Animal and Poultry Sciences
Pasteurella multocida
fowl cholera
serotype
vaccine
lipopolysaccharides
PCR
lectin
Vaccine-related fowl cholera must be considered when flock mortality increases after use of a live Pasteurella multocida vaccine product. All registered live vaccines serotype as Heddleston 3,4; however, in some regions this is also the most common scrotype of outbreak isolates in broiler breeders and turkeys. Therefore, serotyping may not be useful for diagnosing vaccine-related fowl cholera. This project sought to apply a vaccine-specific test to differentiate vaccine-related disease from naturally occurring outbreaks. Results indicate that vaccine strains were commonly isolated from broiler breeders exhibiting signs of fowl cholera postvaccination, but some of these isolates exhibited only serotype 4 antigenicity. The isolates' lipopolysaccharides, the target antigen for serotyping, contained compositional changes that may explain the varying serotype results and virulence of the commercial preparations. These results suggest that vaccine-related disease may be common in broiler breeders, and live commercial vaccine preparations need to be assessed for serotype and titer prior to use in order to reduce vaccine-related fowl cholera.
2021-03-05T14:58:25Z
2021-03-05T14:58:25Z
2021-03-05T14:58:25Z
2020-12
Article - Refereed
0005-2086
http://hdl.handle.net/10919/102619
https://doi.org/10.1637/aviandiseases-D-20-00024
64
4
33347552
1938-4351
en
http://creativecommons.org/publicdomain/mark/1.0/
Public Domain
oai:vtechworks.lib.vt.edu:10919/1165252023-10-24T07:12:30Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Gnotobiotic pig models: Illuminating the enigma of human norovirus infection and immunity
Yuan, Lijuan
2023-10-23T13:41:56Z
2023-10-23T13:41:56Z
2023-10-23T13:41:56Z
2023-10-02
Article
http://hdl.handle.net/10919/116525
Yuan, Lijuan [0000-0003-0709-5228]
en
https://www.openaccessgovernment.org/article/gnotobiotic-pig-models-illuminating-the-enigma-of-human-norovirus-infection-and-immunity/167491/#:~:text=Gn%20pig%20models%20have%20emerged,murine%20models%20and%20human%20systems.
https://www.openaccessgovernment.org/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Open Access Government
oai:vtechworks.lib.vt.edu:10919/479822023-06-14T17:01:29Zcom_10919_78629com_10919_78628com_10919_24216com_10919_5539com_10919_24259com_10919_5559com_10919_24233com_10919_5532com_10919_23765com_10919_23274col_10919_78630col_10919_24286col_10919_24342col_10919_24308col_10919_24353col_10919_23275
Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis
Salmanzadeh, Alireza
Kittur, Harsha
Sano, Michael B.
Roberts, Paul C.
Schmelz, Eva M.
Davalos, Rafael V.
Biomedical Engineering and Mechanics
Biomedical Sciences and Pathobiology
Human Nutrition, Foods, and Exercise
Institute for Critical Technology and Applied Science
School of Biomedical Engineering and Sciences
Force microscopy
Breast cancer
Dielectrics
Stem-cells
Separation
Blood
Electrorotation
Biomarkers
Frequency
Membranes
Biochemical research methods
Biophysics
Nanoscience & nanotechnology
Physics, fluids & plasmas
Ovarian cancer is the leading cause of death from gynecological malignancies in women. The primary challenge is the detection of the cancer at an early stage, since this drastically increases the survival rate. In this study we investigated the dielectrophoretic responses of progressive stages of mouse ovarian surface epithelial (MOSE) cells, as well as mouse fibroblast and macrophage cell lines, utilizing contactless dielectrophoresis (cDEP). cDEP is a relatively new cell manipulation technique that has addressed some of the challenges of conventional dielectrophoretic methods. To evaluate our microfluidic device performance, we computationally studied the effects of altering various geometrical parameters, such as the size and arrangement of insulating structures, on dielectrophoretic and drag forces. We found that the trapping voltage of MOSE cells increases as the cells progress from a non-tumorigenic, benign cell to a tumorigenic, malignant phenotype. Additionally, all MOSE cells display unique behavior compared to fibroblasts and macrophages, representing normal and inflammatory cells found in the peritoneal fluid. Based on these findings, we predict that cDEP can be utilized for isolation of ovarian cancer cells from peritoneal fluid as an early cancer detection tool. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3699973] Actual pdf downloaded from NCBI.
2014-05-14T13:35:38Z
2014-05-14T13:35:38Z
2014-05-14T13:35:38Z
2012-06-01
Article - Refereed
Salmanzadeh, A.; Kittur, H.; Sano, M. B.; Roberts, P. C.; Schmelz, E. M.; Davalos, R. V., "Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis," Biomicrofluidics 6, 024104 (2012); http://dx.doi.org/10.1063/1.3699973
1932-1058
http://hdl.handle.net/10919/47982
http://scitation.aip.org/content/aip/journal/bmf/6/2/10.1063/1.3699973
https://doi.org/10.1063/1.3699973
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Institute of Physics
oai:vtechworks.lib.vt.edu:10919/1000372023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus
Mohamed, Mohamed F.
AbdelKhalek, Ahmed
Seleem, Mohamed N.
SOFT-TISSUE INFECTIONS
PERSISTER CELLS
ANTIBIOTICS
MECHANISMS
DISEASE
SKIN
EPIDERMIDIS
VANCOMYCIN
PEXIGANAN
PENETRATION
Methicillin-resistant Staphylococcus aureus (MRSA) infections present a serious challenge because of the emergence of resistance to numerous conventional antibiotics. Due to their unique mode of action, antimicrobial peptides are novel alternatives to traditional antibiotics for tackling the issue of bacterial multidrug resistance. Herein, we investigated the antibacterial activity of two short novel peptides (WR12, a 12 residue peptide composed exclusively of arginine and tryptophan, and D-IK8, an eight residue β-sheet peptide) against multidrug resistant staphylococci. In vitro, both peptides exhibited good antibacterial activity against MRSA, vancomycin-resistant S. aureus, linezolid-resistant S. aureus, and methicillin-resistant S. epidermidis. WR12 and D-IK8 were able to eradicate persisters, MRSA in stationary growth phase, and showed significant clearance of intracellular MRSA in comparison to both vancomycin and linezolid. In vivo, topical WR12 and D-IK8 significantly reduced both the bacterial load and the levels of the pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in MRSA-infected skin lesions. Moreover, both peptides disrupted established in vitro biofilms of S. aureus and S. epidermidis significantly more so than traditional antimicrobials tested. Taken together, these results support the potential of WR12 and D-IK8 to be used as a topical antimicrobial agent for the treatment of staphylococcal skin infections.
2020-09-21T16:15:31Z
2020-09-21T16:15:31Z
2020-09-21T16:15:31Z
2016-07-11
Article - Refereed
2045-2322
srep29707 (PII)
http://hdl.handle.net/10919/100037
https://doi.org/10.1038/srep29707
6
1
Seleem, Mohamed [0000-0003-0939-0458]
27405275 (pubmed)
2045-2322
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Nature Publishing Group
oai:vtechworks.lib.vt.edu:10919/919062023-11-29T19:08:00Zcom_10919_8195com_10919_25799com_10919_5540com_10919_24259com_10919_5559com_10919_91912com_10919_23198col_10919_18629col_10919_71752col_10919_24342col_10919_91916col_10919_23146
Pregnancy and lactation interfere with the response of autoimmunity to modulation of gut microbiota
Mu, Qinghui
Cabana-Puig, Xavier
Mao, Jiangdi
Swartwout, Brianna K.
Abdelhamid, Leila
Cecere, Thomas E.
Wang, Haifeng
Reilly, Christopher M.
Luo, Xin M.
Background
Dysbiosis of gut microbiota exists in the pathogenesis of many autoimmune diseases, including systemic lupus erythematosus (lupus). Lupus patients who experienced pregnancy usually had more severe disease flares post-delivery. However, the possible role of gut microbiota in the link between pregnancy and exacerbation of lupus remains to be explored.
Results
In the classical lupus mouse model MRL/lpr, we compared the structures of gut microbiota in pregnant and lactating individuals vs. age-matched naïve mice. Consistent with studies on non-lupus mice, both pregnancy and lactation significantly changed the composition and diversity of gut microbiota. Strikingly, modulation of gut microbiota using the same strategy resulted in different disease outcomes in postpartum (abbreviated as “PP,” meaning that the mice had undergone pregnancy and lactation) vs. control (naïve; i.e., without pregnancy or lactation) MRL/lpr females; while vancomycin treatment attenuated lupus in naïve mice, it did not do so, or even exacerbated lupus, in PP mice. Lactobacillus animalis flourished in the gut upon vancomycin treatment, and direct administration of L. animalis via oral gavage recapitulated the differential effects of vancomycin in PP vs. control mice. An enzyme called indoleamine 2,3-dioxygenase was significantly inhibited by L. animalis; however, this inhibition was only apparent in PP mice, which explained, at least partially, the lack of beneficial response to vancomycin in these mice. The differential production of immunosuppressive IL-10 and proinflammatory IFNγ in PP vs. control mice further explained why the disease phenotypes varied between the two types of mice bearing the same gut microbiota remodeling strategy.
Conclusions
These results suggest that pregnancy and lactation interfere with the response of autoimmunity to modulation of gut microbiota. Further studies are necessary to better understand the complex relationship between pregnancy and lupus.
2019-07-22T12:01:48Z
2019-07-22T12:01:48Z
2019-07-22T12:01:48Z
2019-07-16
Article - Refereed
Microbiome. 2019 Jul 16;7(1):105
http://hdl.handle.net/10919/91906
https://doi.org/10.1186/s40168-019-0720-8
en
http://creativecommons.org/licenses/by/4.0/
The Author(s)
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/786562023-12-11T11:08:15Zcom_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_18629col_10919_24342
Increased frequency of porcine epidemic diarrhea virus shedding and lesions in suckling pigs compared to nursery pigs and protective immunity in nursery pigs after homologous re-challenge
Gerber, Priscilla F.
Xiao, Chao-Ting
Lager, Kelly
Crawford, Kimberly
Kulshreshtha, Vikas
Cao, Dianjun
Meng, Xiang-Jin
Opriessnig, Tanja
Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs and spreads rapidly after entering naïve pig populations. The objectives were to (1) compare the disease course following inoculation with PEDV isolate US/Colorado/2013 in naïve 10 day and 8 week-old pigs, and (2) contrast the naïve response to homologous challenge in 8 week-old pigs. Pigs were randomly assigned into group 1 (n = 40, no PEDV exposure), group 2 (n = 43, PEDV inoculation at 10 days of age) and group 3 (n = 48, PEDV inoculation at 8 weeks of age). Thirty-three group 2 pigs received a homologous challenge at 8 weeks of age. Following primary or secondary inoculation, 3–10 pigs were euthanized at days post-inoculation (dpi) 1, 2, 3, 7 or 14. Clinical signs were more pronounced in 10 day-old pigs compared to 8 week-old pigs at dpi 2 and 3, a higher number of 10 day-old pigs shed PEDV RNA in feces compared to 8 week-old pigs. Typical severe atrophic enteritis of PEDV infection was observed at dpi 3 in both age groups, and at dpi 4 and 14 fecal shedding patterns were also similar. While both age groups had seroconverted to PEDV by dpi 14, IgG levels were higher in 8 week-old pigs. PEDV IgA antibodies were detected in feces of approximately 50% of the pigs at dpi 44. In homologous challenged pigs, no clinical signs or lesions were found, and PEDV fecal shedding was restricted to less than 10% of the pigs indicating the existence of homologous protection 44 days after initial PEDV exposure.
2017-08-03T20:13:24Z
2017-08-03T20:13:24Z
2017-08-03T20:13:24Z
2016-11-21
Article - Refereed
Veterinary Research. 2016 Nov 21;47(1):118
http://hdl.handle.net/10919/78656
https://doi.org/10.1186/s13567-016-0402-5
en
http://creativecommons.org/licenses/by/4.0/
The Author(s)
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/1075262022-01-12T08:11:24Zcom_10919_78629com_10919_78628com_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_78630col_10919_78882col_10919_24342
Potential Role of Flavivirus NS2B-NS3 Proteases in Viral Pathogenesis and Anti-flavivirus Drug Discovery Employing Animal Cells and Models: A Review
Wahaab, Abdul
Mustafa, Bahar E
Hameed, Muddassar
Stevenson, Nigel J.
Anwar, Muhammad Naveed
Liu, Ke
Wei, Jianchao
Qiu, Yafeng
Ma, Zhiyong
Flaviviruses are known to cause a variety of diseases in humans in different parts of the world. There are very limited numbers of antivirals to combat flavivirus infection, and therefore new drug targets must be explored. The flavivirus NS2B-NS3 proteases are responsible for the cleavage of the flavivirus polyprotein, which is necessary for productive viral infection and for causing clinical infections; therefore, they are a promising drug target for devising novel drugs against different flaviviruses. This review highlights the structural details of the NS2B-NS3 proteases of different flaviviruses, and also describes potential antiviral drugs that can interfere with the viral protease activity, as determined by various studies. Moreover, optimized in vitro reaction conditions for studying the NS2B-NS3 proteases of different flaviviruses may vary and have been incorporated in this review. The increasing availability of the in silico and crystallographic/structural details of flavivirus NS2B-NS3 proteases in free and drug-bound states can pave the path for the development of promising antiflavivirus drugs to be used in clinics. However, there is a paucity of information available on using animal cells and models for studying flavivirus NS2B-NS3 proteases, as well as on the testing of the antiviral drug efficacy against NS2B-NS3 proteases. Therefore, on the basis of recent studies, an effort has also been made to propose potential cellular and animal models for the study of flavivirus NS2B-NS3 proteases for the purposes of exploring flavivirus pathogenesis and for testing the efficacy of possible drugs targets, in vitro and in vivo.
2022-01-11T13:47:44Z
2022-01-11T13:47:44Z
2022-01-11T13:47:44Z
2021-12-28
Article - Refereed
Wahaab, A.; Mustafa, B.E.; Hameed, M.; Stevenson, N.J.; Anwar, M.N.; Liu, K.; Wei, J.; Qiu, Y.; Ma, Z. Potential Role of Flavivirus NS2B-NS3 Proteases in Viral Pathogenesis and Anti-flavivirus Drug Discovery Employing Animal Cells and Models: A Review. Viruses 2021, 14, 44.
http://hdl.handle.net/10919/107526
https://doi.org/10.3390/v14010044
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/1119572022-09-23T07:17:02Zcom_10919_78629com_10919_78628com_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_78630col_10919_78882col_10919_24342
Probiotic as Adjuvant Significantly Improves Protection of the Lanzhou Trivalent Rotavirus Vaccine against Heterologous Challenge in a Gnotobiotic Pig Model of Human Rotavirus Infection and Disease
Parreno, Viviana
Bai, Muqun
Liu, Fangning
Jing, Jiqiang
Olney, Erika
Li, Guohua
Wen, Ke
Yang, Xingdong
Castellucc, Tammy Bui
Kocher, Jacob F.
Zhou, Xu
Yuan, Lijuan
This preclinical study in the gnotobiotic (Gn) pig model of human rotavirus (HRV) infection and disease evaluates the effect of probiotic <i>Lactobacillus rhamnosus</i> GG (LGG) as a mucosal adjuvant on the immunogenicity and cross-protective efficacy of the Lanzhou live oral trivalent (G2, G3, G4) vaccine (TLV, aka LLR3). Gn pigs were immunized with three doses of TLV with or without concurrent administration of nine doses of LGG around the time of the first dose of the TLV vaccination, and were challenged orally with the virulent heterotypic Wa G1P[8] HRV. Three doses of TLV were highly immunogenic and conferred partial protection against the heterotypic HRV infection. LGG significantly enhanced the intestinal and systemic immune responses and improved the effectiveness of protection against the heterotypic HRV challenge-induced diarrhea and virus shedding. In conclusion, we demonstrated the immune-stimulating effects of probiotic LGG as a vaccine adjuvant and generated detailed knowledge regarding the cross-reactive and type-specific antibody and effector B and T cell immune responses induced by the TLV. Due to the low cost, ease of distribution and administration, and favorable safety profiles, LGG as an adjuvant has the potential to play a critical role in improving rotavirus vaccine efficacy and making the vaccines more cost-effective.
2022-09-22T13:16:36Z
2022-09-22T13:16:36Z
2022-09-22T13:16:36Z
2022-09-14
Article - Refereed
Parreno, V.; Bai, M.; Liu, F.; Jing, J.; Olney, E.; Li, G.; Wen, K.; Yang, X.; Castellucc, T.B.; Kocher, J.F.; Zhou, X.; Yuan, L. Probiotic as Adjuvant Significantly Improves Protection of the Lanzhou Trivalent Rotavirus Vaccine against Heterologous Challenge in a Gnotobiotic Pig Model of Human Rotavirus Infection and Disease. Vaccines 2022, 10, 1529.
http://hdl.handle.net/10919/111957
https://doi.org/10.3390/vaccines10091529
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/1010622020-12-11T08:11:13Zcom_10919_24259com_10919_5559col_10919_24342
Mitofusin 2 regulates neutrophil adhesive migration and the actin cytoskeleton
Zhou, Wenqing
Hsu, Alan Y.
Wang, Yueyang
Syahirah, Ramizah
Wang, Tianqi
Jeffries, Jacob
Wang, Xu
Mohammad, Haroon
Seleem, Mohamed N.
Umulis, David
Deng, Qing
Biomedical Sciences and Pathobiology
Mitochondria
Chemotaxis
Rac
Zebrafish
Actin
Leukocyte
Neutrophils rely on glycolysis for energy production. How mitochondria regulate neutrophil function is not fully understood. Here, we report that mitochondrial outer membrane protein Mitofusin 2 (MFN2) regulates neutrophilhomeostasis andchemotaxis in vivo. Mfn2-deficientneutrophils are released from the hematopoietic tissue, trapped in the vasculature in zebrafish embryos, and not capable of chemotaxis. Consistent with this, human neutrophil-like cells that are deficient for MFN2 fail to arrest on activated endothelium under sheer stress or perform chemotaxis on 2D surfaces. Deletion of MFN2 results in a significant reduction of neutrophil infiltration to the inflamed peritoneal cavity in mice. Mechanistically, MFN2-deficient neutrophil-like cells display disrupted mitochondria-ER interaction, heightened intracellular Ca2+ levels and elevated Rac activation after chemokine stimulation. Restoring a mitochondria-ER tether rescues the abnormal Ca2+ levels, Rac hyperactivation and chemotaxis defect resulting from MFN2 depletion. Finally, inhibition of Rac activation restores chemotaxis in MFN2-deficient neutrophils. Taken together, we have identified that MFN2 regulates neutrophil migration via maintaining the mitochondria-ER interaction to suppress Rac activation, and uncovered a previously unrecognized role of MFN2 in regulating cell migration and the actin cytoskeleton. This article has an associated First Person interview with the first authors of the paper.
2020-12-10T14:36:38Z
2020-12-10T14:36:38Z
2020-12-10T14:36:38Z
2020-09
Article - Refereed
0021-9533
jcs248880
http://hdl.handle.net/10919/101062
https://doi.org/10.1242/jcs.248880
133
17
32788232
1477-9137
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/490382023-06-14T14:38:22Zcom_10919_24259com_10919_5559com_10919_24231com_10919_5532col_10919_24342col_10919_24306
Effect of hydrogen peroxide and other protease inhibitors on Cryptosporidium parvum excystation and in vitro development
Kniel, Kalmia E.
Sumner, Susan S.
Pierson, Merle D.
Zajac, Anne M.
Hackney, Cameron Raj
Fayer, Ronald
Lindsay, David S.
Biomedical Sciences and Pathobiology
Food Science and Technology
proteolytic activity
proteinase activity
serine-protease
oocysts
sporozoites
cells
invasion
identification
inactivation
merozoites
parasitology
This study was undertaken to observe the effects of hydrogen peroxide on Cryptosporidium parvum oocysts with respect to protease activity in comparison to known protease inhibitors. In assessing the possible mechanisms of action of hydrogen peroxide, treatment effectiveness was analyzed using 3 assays and the potential roles of proteases and cations were considered. Treatment of C. parvum oocysts with hydrogen peroxide inhibited protease activity up to 50% compared with untreated controls. Treatment of oocysts with chemicals that affect sulfhydryls, including N-ethylmaleimide and dithiolthreitol, inhibited protease activity by > 90%. Treatment of oocysts with these chemicals, along with the protease inhibitors, phenylmethylsulfonyl fluoride (PMSF), ethylenediamine-tetraacetic acid, and cystatin, inhibited protease activity as well as in vitro excystation and infection in a cell culture assay. Several mechanisms may result in the successful inhibition of infection and excystation by hydrogen peroxide treatment, including: oxidation of oocyst wall proteins or lipids, chelating of cations necessary for infection, or hydroxyl radical-induced DNA damage to sporozoites, or both.
2014-06-20T14:13:12Z
2014-06-20T14:13:12Z
2014-06-20T14:13:12Z
2004-08
Article - Refereed
K. E. Kniel, S. S. Sumner, M. D. Pierson, A. M. Zajac, C. R. Hackney, R. Fayer, and D. S. Lindsay (2004). 'Effect of Hydrogen Peroxide and Other Protease Inhibitors on Cryptosporidium parvum Excystation and In Vitro Development," Journal of Parasitology, Vol. 90, No. 4, pp. 885-888. doi: http://dx.doi.org/10.1645/GE-203R1
0022-3395
http://hdl.handle.net/10919/49038
http://www.bioone.org/doi/abs/10.1645/GE-203R1
https://doi.org/10.1645/ge-203r1
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/740222024-03-12T15:58:56Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Non-inflammasome forming NLRs in inflammation and tumorigenesis
Allen, Irving C.
Immunology
Nod-like receptors
NLRP12
NLRX1
NLRC3
NF-kappa B,TRAF
cancer
pattern recognition receptors
NF-KAPPA-B
INNATE IMMUNE-SYSTEM
CUTTING EDGE
LISTERIA-MONOCYTOGENES
SIGNALING PATHWAYS
NALP3 INFLAMMASOME
COLON INFLAMMATION
INDUCED ACTIVATION
BREAST-CARCINOMA
MELANOMA-CELLS
Aberrant inflammation is an enabling characteristic of tumorigenesis. Thus, signaling cascades that alter inflammatory activation and resolution are of specific relevance to disease pathogenesis. Pattern recognition receptors (PRRs) are essential mediators of the host immune response and have emerged as critical elements affecting multiple facets of tumor pathobiology. The nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins are intracellular PRRs that sense microbial and non-microbial products. Members of the NLR family can be divided into functional sub-groups based on their ability to either positively or negatively regulate the host immune response. Recent studies have identified a novel sub-group of non-inflammasome forming NLRs that negatively regulate diverse biological pathways associated with both inflammation and tumorigenesis. Understanding the mechanisms underlying the function of these unique NLRs will assist in the rationale design of future therapeutic strategies targeting a wide spectrum of inflammatory diseases and cancer. Here, we will discuss recent findings associated with this novel NLR sub-group and mechanisms by which these PRRs may function to alter cancer pathogenesis.
2017-01-08T21:33:53Z
2017-01-08T21:33:53Z
2017-01-08T21:33:53Z
2014-04-22
Article - Refereed
Review
1664-3224
http://hdl.handle.net/10919/74022
https://doi.org/10.3389/fimmu.2014.00169
5
en
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000354134500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1
http://creativecommons.org/licenses/by/3.0/
Creative Commons Attribution 3.0 Unported
Frontiers
oai:vtechworks.lib.vt.edu:10919/1000222023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Screening of Natural Products and Approved Oncology Drug Libraries for Activity against Clostridioides difficile
Pal, Rusha
Seleem, Mohamed N.
TOXIN-B
INFECTION
EPIDEMIOLOGY
VIRULENCE
METRONIDAZOLE
FIDAXOMICIN
INHIBITION
VANCOMYCIN
MICROBIOTA
MECHANISM
Clostridioides difficile is the most common cause of healthcare-associated diarrhea. Infection of the gastrointestinal tract with this Gram-positive, obligate anaerobe can lead to potentially life-threatening conditions in the antibiotic-treated populace. New therapeutics are urgently needed to treat this infection and prevent its recurrence. Here, we screened two libraries from the National Cancer Institute, namely, the natural product set III library (117 compounds) and the approved oncology drugs set V library (114 compounds), against C. difficile. In the two libraries screened, 17 compounds from the natural product set III library and 7 compounds from the approved oncology drugs set V library were found to exhibit anticlostridial activity. The most potent FDA-approved drugs (mitomycin C and mithramycin A) and a promising natural product (aureomycin) were further screened against 20 clinical isolates of C. difficile. The anticancer drugs, mitomycin C (MIC50 = 0.25 μg/ml) and mithramycin A (MIC50 = 0.015 μg/ml), and the naturally derived tetracycline derivative, aureomycin (MIC50 = 0.06 μg/ml), exhibited potent activity against C. difficile strains. Mithramycin A and aureomycin were further found to inhibit toxin production by this pathogen. Given their efficacy, these compounds can provide a quick supplement to current treatment to address the unmet needs in treating C. difficile infection and preventing its recurrence.
2020-09-21T16:11:16Z
2020-09-21T16:11:16Z
2020-09-21T16:11:16Z
2020-04-06
Article - Refereed
2045-2322
10.1038/s41598-020-63029-0 (PII)
http://hdl.handle.net/10919/100022
https://doi.org/10.1038/s41598-020-63029-0
10
1
Seleem, Mohamed [0000-0003-0939-0458]
32249833 (pubmed)
2045-2322
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Nature Publishing Group
oai:vtechworks.lib.vt.edu:10919/490372023-12-19T13:34:26Zcom_10919_78629com_10919_78628com_10919_24259com_10919_5559com_10919_18738com_10919_5539col_10919_78791col_10919_24342col_10919_23145
Dopamine Stimulates Propagation of Toxoplasma gondii Tachyzoites in Human Fibroblast and Primary Neonatal Rat Astrocyte Cell Cultures
Strobl, Jeannine S.
Goodwin, David G.
Rzigalinski, Beverly A.
Lindsay, David S.
Electrical and Computer Engineering
Biomedical Sciences and Pathobiology
Human-skin fibroblasts
Behavioral abnormalities
Monoamine-oxidase
Decreased level
Novelty seeking
Infected mice
Acid
Cytomegalovirus
Schizophrenia
Disorders
Parasitology
Toxoplasma gondii is an obligate intracellular parasite often found in the brain of humans. Research has shown a correlation between prevalence of antibody titers to T. gondii and psychological illness in humans. Recent studies indicate that individuals seropositive for T. gondii antibodies are more likely to develop psychotic disorders including schizophrenia, which is associated with changes in the dopamine neurotransmitter system. Dopamine in the brain may play a role in proliferation, chemoattraction, infection efficiency, or stage conversion of T. gondii. Because tachyzoites are the first developmental stage to reach the brain, the present study was conducted to determine the effects of dopamine on their development in vitro. In human fibroblast host cells, dopamine was added at either 100 nM or 250 nM to cell culture media, and the numbers of tachyzoites produced at 48 hr were determined and compared to vehicle-treated controls. An increase of tachyzoite numbers and increased destruction in cell monolayer were observed at both concentrations of dopamine. Dopamine used at 250 nM caused a significant (P < 0.05) increase in tachyzoites counts compared to controls. Dopamine antagonists (10 mu M) did not significantly alter dopamine-stimulated tachyzoite production in human fibroblasts. In primary neonatal rat astrocyte cell cultures, dopamine (200 mu M) significantly (P < 0.05) increased numbers of intracellular tachyzoites after 24 hr. The role that this increase plays in tachyzoite production under the stimulus of dopamine in the modulation of neural infection in humans awaits further studies.
2014-06-20T14:13:12Z
2014-06-20T14:13:12Z
2014-06-20T14:13:12Z
2012-12-01
Article - Refereed
Jeannine S. Strobl, David G. Goodwin, Beverly A. Rzigalinski, and David S. Lindsay (2012). "Dopamine Stimulates Propagation of Toxoplasma gondii Tachyzoites in Human Fibroblast and Primary Neonatal Rat Astrocyte Cell Cultures," Journal of Parasitology, Vol. 98, No. 6, pp. 1296-1299. doi: http://dx.doi.org/10.1645/GE-2760.1
0022-3395
http://hdl.handle.net/10919/49037
http://www.bioone.org/doi/abs/10.1645/GE-2760.1
https://doi.org/10.1645/ge-2760.1
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Society of Parasitology
oai:vtechworks.lib.vt.edu:10919/928862023-12-12T14:54:57Zcom_10919_24259com_10919_5559com_10919_24263col_10919_24342col_10919_24345
A Comparison of Liver Sampling Techniques in Dogs
Kemp, Stephanie D.
Zimmerman, Kurt L.
Panciera, David L.
Monroe, William E.
Leib, Michael S.
Lanz, Otto I.
Fibrosis
Hepatitis
Laparoscopy
Needle biopsy
Background: The liver sampling technique in dogs that consistently provides samples adequate for accurate histopathologic interpretation is not known.
Hypothesis/ Objectives: To compare histopathologic results of liver samples obtained by punch, cup, and 14 gauge needle to large wedge samples collected at necropsy.
Animals: Seventy dogs undergoing necropsy.
Methods: Prospective study. Liver specimens were obtained from the left lateral liver lobe with an 8 mm punch, a 5 mm cup, and a 14 gauge needle. After sample acquisition, two larger tissue samples were collected near the center of the left lateral lobe to be used as a histologic standard for comparison. Histopathologic features and numbers of portal triads in each sample were recorded.
Results: The mean number of portal triads obtained by each sampling method were 2.9 in needle samples, 3.4 in cup samples, 12 in punch samples, and 30.7 in the necropsy samples. The diagnoses in 66% of needle samples, 60% of cup samples, and 69% of punch samples were in agreement with the necropsy samples, and these proportions were not significantly different from each other. The corresponding kappa coefficients were 0.59 for needle biopsies, 0.52 for cup biopsies, and 0.62 for punch biopsies.
Conclusion and Clinical Importance: The histopathologic interpretation of a liver sample in the dog is unlikely to vary if the liver biopsy specimen contains at least 3- 12 portal triads. However, in comparison large necropsy samples, the accuracy of all tested methods was relatively low.
2019-08-08T12:44:50Z
2019-08-08T12:44:50Z
2019-08-08T12:44:50Z
2015-01
Article - Refereed
0891-6640
http://hdl.handle.net/10919/92886
https://doi.org/10.1111/jvim.12508
29
1
25417960
1939-1676
en
http://creativecommons.org/licenses/by-nc/4.0/
Creative Commons Attribution-NonCommercial 4.0 International
American College of Veterinary Internal Medicine
oai:vtechworks.lib.vt.edu:10919/496512023-12-19T13:34:26Zcom_10919_24259com_10919_5559col_10919_24342
Besnoitia oryctofelisi n. sp (Protozoa : Apicomplexa) from domestic rabbits
Dubey, Jitender P.
Sreekumar, C.
Lindsay, David S.
Hill, D.
Rosenthal, B. M.
Venturini, L.
Venturini, M. C.
Greiner, E. C.
besnoitia oryctofelisi
n. sp.
b. darlingi
rabbits
cats
gerbils
mice
schizonts
cell culture
argentina
opossum didelphis-marsupialis
rangifer-tarandus-tarandus
experimental
intermediate
sarcocystis-falcatula
caprine besnoitiosis
electron-microscopy
cyclic transmission
cell cultures
jellisoni
darlingi
parasitology
A species of Besnoitia from naturally infected rabbits from Argentina was propagated experimentally in mice, gerbils, rabbits, cats, and cell cultures. Cats fed tissue cysts from rabbits shed oocysts with a prepatent period of nine to 13 days. Sporulated oocysts were infective to gerbils, rabbits, outbred Swiss Webster and interferon gamma gene knockout mice. Bradyzoites were infective orally to gerbils and cats. Tachyzoites were successfully cultivated and maintained in vitro in bovine monocytes and African green monkey kidney cells. Schizonts were seen in the lamina propria of the small intestine of cats fed tissue cysts; the largest ones measured 52 x 45 mum. Schizonts were also present in mesenteric lymph nodes, livers, and other extra-intestinal organs of cats fed tissue cysts. Oocysts were 10-14 x 10-13 mum in size. This rabbit-derived species of Besnoitia resembled B. darlingi of the North American opossum, Didelphis virginiana with an opossum-cat cycle, but it was not transmissible to D. virginiana, and B. darlingi of opossums was not transmissible to rabbits. Based on biological, serological, antigenic, and molecular differences between the rabbit and the opossum Besnoitia, a new name, B. oryctofelisi is proposed for the parasite from domestic rabbits from Argentina.
2014-07-21T15:49:43Z
2014-07-21T15:49:43Z
2014-07-21T15:49:43Z
2003-06
Article - Refereed
Dubey, J. P.; Sreekumar, C.; et al., "Besnoitia oryctofelisi n. sp (Protozoa : Apicomplexa) from domestic rabbits," Parasitology (2003), 126, 521-539. DOI: 10.1017/s0031182003003123
0031-1820
http://hdl.handle.net/10919/49651
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=152109&fulltextType=RA&fileId=S0031182003003123
https://doi.org/10.1017/s0031182003003123
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
Cambridge University Press
oai:vtechworks.lib.vt.edu:10919/1039872021-10-08T16:43:32Zcom_10919_8195com_10919_25799com_10919_24259com_10919_5559col_10919_78882col_10919_24342
A Natural Botanical Product, Resveratrol, Effectively Suppresses Vesicular Stomatitis Virus Infection In Vitro
Lin, Shih-Chao
Zhang, Xiang
Lehman, Caitlin W.
Pan, Han-Chi
Wen, Ya
Chen, Shiow-Yi
Biomedical Sciences and Pathobiology
resveratrol
vesicular stomatitis virus
antiviral activity
veterinary science
husbandry farming
Numerous natural phytochemicals such as resveratrol are acknowledged as potent botanical agents in regulating immune responses. However, it is less understood whether such immunomodulatory phytochemicals are appropriate for use as direct treatments in veterinary viral diseases. In the present study, we investigated the efficacy of resveratrol in suppressing vesicular stomatitis virus (VSV) infection. Outbreaks of VSV can cause massive economic loss in poultry and livestock husbandry farming, and VSV treatment is in need of therapeutic development. We utilized a recombinant VSV that expresses green fluorescent protein (GFP) to measure viral replication in cells treated with resveratrol. Our findings revealed that resveratrol treatment affords a protective effect, shown by increased viability and reduced viral replication, as indicated by a reduction in fluorescent signals. Additionally, we found that resveratrol inhibition of VSV infection occurs via suppression of the caspase cascade. Structural analysis also indicated that resveratrol potentially interacts with the active sites of caspase-3 and -7, facilitating antiviral activity. The potential effect of resveratrol on reducing VSV infection in vitro suggests that resveratrol should be further investigated as a potential veterinary therapeutic or prophylactic agent.
2021-06-24T14:54:16Z
2021-06-24T14:54:16Z
2021-06-24T14:54:16Z
2021-06-17
Article - Refereed
Lin, S.-C.; Zhang, X.; Lehman, C.W.; Pan, H.-C.; Wen, Y.; Chen, S.-Y. A Natural Botanical Product, Resveratrol, Effectively Suppresses Vesicular Stomatitis Virus Infection In Vitro. Plants 2021, 10, 1231.
http://hdl.handle.net/10919/103987
https://doi.org/10.3390/plants10061231
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/1000492023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_78629com_10919_78628com_10919_24259com_10919_5559col_10919_70873col_10919_78791col_10919_24342
Effects of Chronic Social Stress and Maternal Intranasal Oxytocin and Vasopressin on Offspring Interferon-gamma and Behavior
Murgatroyd, Christopher A.
Hicks-Nelson, Alexandria
Fink, Alexandria
Beamer, Gillian
Gurel, Kursat
Elnady, Fawzy
Pittet, Florent
Nephew, Benjamin C.
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
social stress
depression
depression and anxiety disorders
interferon-gamma
oxytocin
vasopressin
social behavior
inflammation
V1A RECEPTOR ANTAGONIST
ARGININE-VASOPRESSIN
GENE-EXPRESSION
CARE
RATS
DEPRESSION
AGGRESSION
PROLACTIN
ANXIETY
CORTICOSTERONE
1103 Clinical Sciences
1111 Nutrition and Dietetics
Recent studies support the hypothesis that the adverse effects of early-life adversity and transgenerational stress on neural plasticity and behavior are mediated by inflammation. The objective of the present study was to investigate the immune and behavioral programing effects of intranasal (IN) vasopressin (AVP) and oxytocin (OXT) treatment of chronic social stress (CSS)-exposed F1 dams on F2 juvenile female offspring. It was hypothesized that maternal AVP and OXT treatment would have preventative effects on social stress-induced deficits in offspring anxiety and social behavior and that these effects would be associated with changes in interferon-γ (IFNγ). Control and CSS-exposed F1 dams were administered IN saline, AVP, or OXT during lactation and the F2 juvenile female offspring were assessed for basal plasma IFNγ and perseverative, anxiety, and social behavior. CSS F2 female juvenile offspring had elevated IFNγ levels and exhibited increased repetitive/perseverative and anxiety behaviors and deficits in social behavior. These effects were modulated by AVP and OXT in a context- and behavior-dependent manner, with OXT exhibiting preventative effects on repetitive and anxiety behaviors and AVP possessing preventative effects on social behavior deficits and anxiety. Basal IFNγ levels were elevated in the F2 offspring of OXT-treated F1 dams, but IFNγ was not correlated with the behavioral effects. These results support the hypothesis that maternal AVP and OXT treatment have context- and behavior-specific effects on peripheral IFNγ levels and perseverative, anxiety, and social behaviors in the female offspring of early-life social stress-exposed dams. Both maternal AVP and OXT are effective at preventing social stress-induced increases in self-directed measures of anxiety, and AVP is particularly effective at preventing impairments in overall social contact. OXT is specifically effective at preventing repetitive/perseverative behaviors, yet is ineffective at preventing deficits in overall social behavior.
2020-09-21T18:57:57Z
2020-09-21T18:57:57Z
2020-09-21T18:57:57Z
2016-12-14
Article
1664-2392
http://hdl.handle.net/10919/100049
https://doi.org/10.3389/fendo.2016.00155
7
Elnady, Fawzy [0000-0003-4282-7949]
28018290 (pubmed)
1664-2392
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Frontiers
oai:vtechworks.lib.vt.edu:10919/751252023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_5540com_10919_24259com_10919_5559col_10919_70873col_10919_71752col_10919_24342
Enterobacter cloacae inhibits human norovirus infectivity in gnotobiotic pigs
Lei, Shaohua
Samuel, Helen
Twitchell, Erica
Bui, Tammy
Ramesh, Ashwin
Wen, Ke
Weiss, Mariah
Li, Guohua
Yang, Xingdong
Jiang, Xi
Yuan, Lijuan
Human noroviruses (HuNoVs) are the leading cause of epidemic gastroenteritis worldwide. Study of HuNoV biology has been hampered by the lack of an efficient cell culture system. Recently, enteric commensal bacteria Enterobacter cloacae has been recognized as a helper in HuNoV infection of B cells in vitro. To test the influences of E. cloacae on HuNoV infectivity and to determine whether HuNoV infects B cells in vivo, we colonized gnotobiotic pigs with E. cloacae and inoculated pigs with 2.74 × 10(4) genome copies of HuNoV. Compared to control pigs, reduced HuNoV shedding was observed in E. cloacae colonized pigs, characterized by significantly shorter duration of shedding in post-inoculation day 10 subgroup and lower cumulative shedding and peak shedding in individual pigs. Colonization of E. cloacae also reduced HuNoV titers in intestinal tissues and in blood. In both control and E. cloacae colonized pigs, HuNoV infection of enterocytes was confirmed, however infection of B cells was not observed in ileum, and the entire lamina propria in sections of duodenum, jejunum, and ileum were HuNoV-negative. In summary, E. cloacae inhibited HuNoV infectivity, and B cells were not a target cell type for HuNoV in gnotobiotic pigs, with or without E. cloacae colonization.
2017-02-22T15:38:36Z
2017-02-22T15:38:36Z
2017-02-22T15:38:36Z
2016-04-26
Article - Refereed
http://hdl.handle.net/10919/75125
https://doi.org/10.1038/srep25017
6
2045-2322
en
http://www.ncbi.nlm.nih.gov/pubmed/27113278
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/1159752023-08-04T07:12:07Zcom_10919_24259com_10919_5559com_10919_24262com_10919_24263col_10919_24342col_10919_24344col_10919_24345
Bead size has a greater effect on in vitro elution from antimicrobial-impregnated calcium sulfate beads than drug concentration
Olsen, Ronald S.
Sawyere, Dominique M.
Davis, Jennifer L.
Lanz, Otto I.
Werre, Stephen R.
OBJECTIVE To compare the elution characteristics of amikacin-impregnated calcium sulfate (CaSO4) beads based on different drug concentrations and bead size configurations. SAMPLE Six groups of amikacin-impregnated CaSO4 beads and one negative control group. PROCEDURES Amikacin-impregnated CaSO4 beads were formed with either 500 mg (low-concentration) or 1 g (high-concentration) of amikacin per 15 g CaSO4 hemihydrate powder. The number of beads necessary to approximate 150 mg of amikacin for each of the 3 bead sizes (3 mm, 5 mm, and 7 mm) at both low and high concentrations were placed in 6 mL of phosphate-buffered saline. The saline was sampled at 14 time points over 28 days. Amikacin concentrations were determined using liquid chromatography-mass spectrometry. RESULTS Smaller beads reached higher mean peak concentrations than larger beads (P < .0006). Peak concentrations for the low-and high-concentration groups were 20.5 mg/mL and 27.4 mg/mL, 13.1 mg/mL and 14.0 mg/mL, and 8.85 mg/mL and 6.75 mg/mL for the 3 mm, 5 mm, and 7 mm beads, respectively. Bead size also affected the length of therapeutic duration, lasting 6 days for the 3 mm and 5 mm beads and 9 days for the 7 mm beads. However, this was only statistically evident among the high-concentration beads (P < .044). Antimicrobial concentration within the same bead sizes did not affect elution. CLINICAL RELEVANCE Amikacin-impregnated CaSO4 beads achieved extreme supratherapeutic eluent concentrations. While additional studies are needed, bead size significantly affected elution with smaller beads reaching higher peak concentrations and 7 mm, high-concentration beads demonstrating a longer therapeutic duration than smaller beads.
2023-08-03T14:39:25Z
2023-08-03T14:39:25Z
2023-08-03T14:39:25Z
2023-05
Article - Refereed
0002-9645
http://hdl.handle.net/10919/115975
https://doi.org/10.2460/ajvr.22.12.0216
84
5
36881500
1943-5681
en
http://creativecommons.org/licenses/by-nc/4.0/
Creative Commons Attribution-NonCommercial 4.0 International
American Veterinary Medical Association
oai:vtechworks.lib.vt.edu:10919/1000302023-12-19T13:34:26Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Photolysis of Staphyloxanthin in Methicillin-Resistant Staphylococcus aureus Potentiates Killing by Reactive Oxygen Species
Dong, Pu-Ting
Mohammad, Haroon
Hui, Jie
Leanse, Leon G.
Li, Junjie
Liang, Lijia
Dai, Tianhong
Seleem, Mohamed N.
Cheng, Ji-Xin
Chemistry, Multidisciplinary
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Chemistry
Materials Science
methicillin-resistant Staphylococcus aureus (MRSA)
phototherapy
staphyloxanthin photobleaching
transient absorption microscopy
BIOSYNTHESIS
MICROBIOLOGY
FLUORESCENCE
CAROTENOIDS
COMBINATION
DAPTOMYCIN
DEPENDENCE
VIRULENCE
BIOFILMS
DRUGS
methicillin‐resistant Staphylococcus aureus (MRSA)
Confronted with the severe situation that the pace of resistance acquisition is faster than the clinical introduction of new antibiotics, health organizations are calling for effective approaches to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, an approach to treat MRSA through photolysis of staphyloxanthin, an antioxidant residing in the microdomain of S. aureus membrane, is reported. This photochemistry process is uncovered through transient absorption imaging and quantitated by absorption spectroscopy, Raman spectroscopy, and mass spectrometry. Photolysis of staphyloxanthin transiently elevates the membrane permeability and renders MRSA highly susceptible to hydrogen peroxide attack. Consequently, staphyloxanthin photolysis by low-level 460 nm light eradicates MRSA synergistically with hydrogen peroxide and other reactive oxygen species. The effectiveness of this synergistic therapy is well validated in MRSA planktonic culture, MRSA-infected macrophage cells, stationary-phase MRSA, persisters, S. aureus biofilms, and two mice wound infection models. Collectively, the work demonstrates that staphyloxanthin photolysis is a new therapeutic platform to treat MRSA infections.
2020-09-21T16:14:00Z
2020-09-21T16:14:00Z
2020-09-21T16:14:00Z
2019-06-05
Article - Refereed
2198-3844
ADVS1026 (PII)
http://hdl.handle.net/10919/100030
https://doi.org/10.1002/advs.201900030
6
11
Seleem, Mohamed [0000-0003-0939-0458]
31179216 (pubmed)
2198-3844
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Wiley
oai:vtechworks.lib.vt.edu:10919/1114112022-08-02T07:11:46Zcom_10919_24259com_10919_5559col_10919_24342
Leptomeningeal anastomoses: Mechanisms of pial collateral remodeling in ischemic stroke
Kaloss, Alexandra M.
Theus, Michelle H.
arteriogenesis
ischemic stroke
large vessel occlusion
leptomeningeal anastomoses
pial collateral
Arterial collateralization, as determined by leptomeningeal anastomoses or pial collateral vessels, is a well-established vital player in cerebral blood flow restoration and neurological recovery from ischemic stroke. A secondary network of cerebral collateral circulation apart from the Circle of Willis, exist as remnants of arteriole development that connect the distal arteries in the pia mater. Recent interest lies in understanding the cellular and molecular adaptations that control the growth and remodeling, or arteriogenesis, of these pre-existing collateral vessels. New findings from both animal models and human studies of ischemic stroke suggest a multi-factorial and complex, temporospatial interplay of endothelium, immune and vessel-associated cell interactions may work in concert to facilitate or thwart arteriogenesis. These valuable reports may provide critical insight into potential predictors of the pial collateral response in patients with large vessel occlusion and may aid in therapeutics to enhance collateral function and improve recovery from stroke. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology
2022-08-01T12:51:19Z
2022-08-01T12:51:19Z
2022-08-01T12:51:19Z
2022-02-03
Article - Refereed
2692-9368
e1553
http://hdl.handle.net/10919/111411
https://doi.org/10.1002/wsbm.1553
35118835
en
http://creativecommons.org/licenses/by-nc-nd/4.0/
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Wiley
oai:vtechworks.lib.vt.edu:10919/1088522022-02-25T13:22:56Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559col_10919_70873col_10919_24342
Progression of diabetes is associated with changes in the ileal transcriptome and ileal-colon morphology in the UC Davis Type 2 Diabetes Mellitus rat
Piccolo, Brian D.
Graham, James L.
Kang, Ping
Randolph, Christopher E.
Shankar, Kartik
Yeruva, Laxmi
Fox, Renee
Robeson, Michael S.
Moody, Becky
LeRoith, Tanya
Stanhope, Kimber L.
Adams, Sean H.
Havel, Peter J.
RNA-seq
UCD-T2DM rat
crypt
diabetes
microbiome
villi
0606 Physiology
1103 Clinical Sciences
1116 Medical Physiology
Deterioration in glucose homeostasis has been associated with intestinal dysbiosis, but it is not known how metabolic dysregulation alters the gastrointestinal environment. We investigated how the progression of diabetes alters ileal and colonic epithelial mucosal structure, microbial abundance, and transcript expression in the University of California Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model. Male UCD-T2DM rats (age ~170 days) were included if <1-month (n = 6, D1M) or 3-month (n = 6, D3M) post-onset of diabetes. Younger nondiabetic UCD-T2DM rats were included as a nondiabetic comparison (n = 6, ND, age ~70 days). Ileum villi height/crypt depths and colon crypt depths were assessed by histology. Microbial abundance of colon content was measured with 16S rRNA sequencing. Ileum and colon transcriptional abundances were analyzed using RNA sequencing. Ileum villi height and crypt depth were greater in D3M rats compared to ND. Colon crypt depth was greatest in D3M rats compared to both ND and D1M rats. Colon abundances of Akkermansia and Muribaculaceae were lower in D3M rats relative to D1M, while Oscillospirales, Phascolarctobacterium, and an unidentified genus of Lachnospiraceae were higher. Only two transcripts were altered by diabetes advancement within the colon; however, 2039 ileal transcripts were altered. Only colonic abundances of Sptlc3, Enpp7, Slc7a15, and Kctd14 had more than twofold changes between D1M and D3M rats. The advancement of diabetes in the UCD-T2DM rat results in a trophic effect on the mucosal epithelia and was associated with regulation of gastrointestinal tract RNA expression, which appears more pronounced in the ileum relative to the colon.
2022-02-24T18:37:37Z
2022-02-24T18:37:37Z
2022-02-24T18:37:37Z
2021-11-01
Article - Refereed
2051-817X
http://hdl.handle.net/10919/108852
https://doi.org/10.14814/phy2.15102
9
22
LeRoith, Tanya [0000-0002-1196-6949]
34806320
2051-817X
en
https://www.ncbi.nlm.nih.gov/pubmed/34806320
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Wiley
oai:vtechworks.lib.vt.edu:10919/734662023-07-13T12:32:34Zcom_10919_5com_10919_25799com_10919_24259com_10919_5559com_10919_23274com_10919_5539com_10919_24263col_10919_70873col_10919_24342col_10919_23275col_10919_24345
Frame-Based Stereotactic Biopsy of Canine Brain Masses: Technique and Clinical Results in 26 Cases
Rossmeisl, John H. Jr.
Andriani, Rudy T.
Cecere, Thomas E.
Lahmers, Kevin K.
LeRoith, Tanya
Zimmerman, Kurt L.
Gibo, Denise M.
Debinski, Waldemar
Biomedical Sciences and Pathobiology
Small Animal Clinical Sciences
School of Biomedical Engineering and Sciences
brain tumor
dog
glioma
neurooncology
neurosurgery
This report describes the methodology, diagnostic yield, and adverse events (AE) associated with frame-based stereotactic brain biopsies (FBSB) obtained from 26 dogs with solitary forebrain lesions. Medical records were reviewed from dogs that underwent FBSB using two stereotactic headframes designed for use in small animals and compatible with computed tomographic (CT) and magnetic resonance (MR) imaging. Stereotactic plans were generated from MR and CT images using commercial software, and FBSB performed both with (14/26) and without intraoperative image guidance. Records were reviewed for diagnostic yield, defined as the proportion of biopsies producing a specific neuropathological diagnosis, AE associated with FBSB, and risk factors for the development of AE. Postprocedural AE were evaluated in 19/26 dogs that did not proceed to a therapeutic intervention immediately following biopsy. Biopsy targets included intra-axial telencephalic masses (24/26), one intra-axial diencephalic mass, and one extra-axial parasellar mass. The median target volume was 1.99 cm(3). No differences in patient, lesion, or outcome variables were observed between the two headframe systems used or between FBSB performed with or without intraoperative CT guidance. The diagnostic yield of FBSB was 94.6%. Needle placement error was a significant risk factor associated with procurement of non-diagnostic biopsy specimens. Gliomas were diagnosed in 24/26 dogs, and meningioma and granulomatous meningoencephalitis in 1 dog each. AE directly related to FBSB were observed in a total of 7/26 (27%) of dogs. Biopsy-associated clinical morbidity, manifesting as seizures and transient neurological deterioration, occurred in 3/19 (16%) of dogs. The case fatality rate was 5.2% (1/19 dogs), with death attributable to intracranial hemorrhage. FBSB using the described apparatus was relatively safe and effective at providing neuropathological diagnoses in dogs with focal forebrain lesions.
2016-11-16T01:51:07Z
2016-11-16T01:51:07Z
2016-11-16T01:51:07Z
2015
Article - Refereed
http://hdl.handle.net/10919/73466
https://doi.org/10.3389/fvets.2015.00020
2
en
http://www.ncbi.nlm.nih.gov/pubmed/26664949
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
oai:vtechworks.lib.vt.edu:10919/967902020-10-22T03:36:23Zcom_10919_24259com_10919_5559com_10919_91918com_10919_84995com_10919_5553col_10919_24342col_10919_91919col_10919_84996
Molecular Phenotyping and Genomic Characterization of a Novel Neuroactive Bacterium Strain, Lactobacillus murinus HU-1
Lebovitz, Yeonwoo
Theus, Michelle H.
Center for Veterinary Regenerative Medicine
Biomedical Sciences and Pathobiology
School of Neuroscience
genome sequence
gut-brain axis
Lactobacillus murinus
microbiome
probiotic
2020-02-10T20:07:05Z
2020-02-10T20:07:05Z
2020-02-10T20:07:05Z
2019-10-04
Article - Refereed
1663-9812
1162
http://hdl.handle.net/10919/96790
https://doi.org/10.3389/fphar.2019.01162
10
31636567
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/967632022-02-26T00:17:14Zcom_10919_78629com_10919_78628com_10919_24259com_10919_5559col_10919_78630col_10919_24342
Host nutritional status affects alphavirus virulence, transmission, and evolution
Weger-Lucarelli, James
Carrau, Lucia
Levi, Laura I.
Rezelj, Veronica V.
Vallet, Thomas
Blanc, Herve
Boussier, Jeremy
Megrian, Daniela
Coutermarsh-Ott, Sheryl
LeRoith, Tanya
Vignuzzi, Marco
Malnourishment, specifically overweight/obesity and undernourishment, affects more than 2.5 billion people worldwide, with the number affected ever-increasing. Concurrently, emerging viral diseases, particularly those that are mosquito-borne, have spread dramatically in the past several decades, culminating in outbreaks of several viruses worldwide. Both forms of malnourishment are known to lead to an aberrant immune response, which can worsen disease outcomes and reduce vaccination efficacy for viral pathogens such as influenza and measles. Given the increasing rates of malnutrition and spread of arthropod-borne viruses (arboviruses), there is an urgent need to understand the role of host nutrition on the infection, virulence, and transmission of these viruses. To address this gap in knowledge, we infected lean, obese, and undernourished mice with arthritogenic arboviruses from the genus Alphavirus and assessed morbidity, virus replication, transmission, and evolution. Obesity and undernourishment did not consistently influence virus replication in the blood of infected animals except for reductions in virus in obese mice late in infection. However, morbidity was increased in obese mice under all conditions. Using Mayaro virus (MAYV) as a model arthritogenic alphavirus, we determined that both obese and undernourished mice transmit virus less efficiently to mosquitoes than control (lean) mice. In addition, viral genetic diversity and replicative fitness were reduced in virus isolated from obese compared to lean controls. Taken together, nutrition appears to alter the course of alphavirus infection and should be considered as a critical environmental factor during outbreaks.
2020-02-07T14:34:40Z
2020-02-07T14:34:40Z
2020-02-07T14:34:40Z
2019-11
Article - Refereed
1553-7366
e1008089
http://hdl.handle.net/10919/96763
https://doi.org/10.1371/journal.ppat.1008089
15
11
31710653
1553-7374
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/1047082023-11-29T11:19:59Zcom_10919_5com_10919_25799com_10919_78629com_10919_78628com_10919_24259com_10919_5559com_10919_103712com_10919_25796col_10919_70873col_10919_78630col_10919_24342col_10919_103713
Structural and molecular biology of hepatitis E virus
Wang, Bo
Meng, Xiang-Jin
Center for Emerging, Zoonotic, and Arthropod-borne Pathogens
Biomedical Sciences and Pathobiology
Genetic Diversity
Genomic organization
Hepatitis E Virus (HEV)
Life cycle of HEV
Proteins and functions
Virion structure
0103 Numerical and Computational Mathematics
0802 Computation Theory and Mathematics
Hepatitis E virus (HEV) is one of the most common causes of acute viral hepatitis, mainly transmitted by fecal-oral route but has also been linked to fulminant hepatic failure, chronic hepatitis, and extrahepatic neurological and renal diseases. HEV is an emerging zoonotic pathogen with a broad host range, and strains of HEV from numerous animal species are known to cross species barriers and infect humans. HEV is a single-stranded, positive-sense RNA virus in the family Hepeviridae. The genome typically contains three open reading frames (ORFs): ORF1 encodes a nonstructural polyprotein for virus replication and transcription, ORF2 encodes the capsid protein that elicits neutralizing antibodies, and ORF3, which partially overlaps ORF2, encodes a multifunctional protein involved in virion morphogenesis and pathogenesis. HEV virions are non-enveloped spherical particles in feces but exist as quasi-enveloped particles in circulating blood. Two types of HEV virus-like particles (VLPs), small T = 1 (270 Å) and native virion-sized T = 3 (320–340 Å) have been reported. There exist two distinct forms of capsid protein, the secreted form (ORF2S) inhibits antibody neutralization, whereas the capsid-associated form (ORF2C) self-assembles to VLPs. Four cis-reactive elements (CREs) containing stem-loops from secondary RNA structures have been identified in the non-coding regions and are critical for virus replication. This mini-review discusses the current knowledge and gaps regarding the structural and molecular biology of HEV with emphasis on the virion structure, genomic organization, secondary RNA structures, viral proteins and their functions, and life cycle of HEV.
2021-08-25T16:17:35Z
2021-08-25T16:17:35Z
2021-08-25T16:17:35Z
2021-01-01
Article - Refereed
2001-0370
PMC8079827
S2001-0370(21)00115-X (PII)
http://hdl.handle.net/10919/104708
https://doi.org/10.1016/j.csbj.2021.03.038
19
Meng, Xiang-Jin [0000-0002-2739-1334]
33995894
2001-0370
en
https://www.ncbi.nlm.nih.gov/pubmed/33995894
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Elsevier
oai:vtechworks.lib.vt.edu:10919/1032602021-05-14T07:15:55Zcom_10919_78629com_10919_78628com_10919_24259com_10919_5559col_10919_78630col_10919_24342
Evaluation of ebselen in resolving a methicillin-resistant Staphylococcus aureus infection of pressure ulcers in obese and diabetic mice
Mohammad, Haroon
Abutaleb, Nader S.
Dieterly, Alexandra M.
Lyle, L. Tiffany
Seleem, Mohamed N.
Biomedical Sciences and Pathobiology
Pressure ulcers (PUs) are a source of morbidity in individuals with restricted mobility including individuals that are obese or diabetic. Infection of PUs with pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), impairs ulcers from healing. The present study evaluated ebselen as a topical antibacterial to treat MRSA-infected PUs. Against two different S. aureus strains, including MRSA USA300, resistance to ebselen did not emerge after 14 consecutive passages. Resistance to mupirocin emerged after only five passages. Additionally, ebselen was found to exert a modest postantibiotic effect of five hours against two MRSA strains. Ebselen was subsequently evaluated in MRSA-infected PUs in two models using obese and diabetic mice. In obese mice, topical ebselen (89.2% reduction) and oral linezolid (84.5% reduction) similarly reduced the burden of MRSA in infected PUs. However, in diabetic mice, topical ebselen (45.8% reduction in MRSA burden) was less effective. Histopathological evaluation of ulcers in diabetic mice determined that ebselen treatment resulted in fewer bacterial colonies deep within the dermis and that the treatment exhibited evidence of epithelial regeneration. Topical mupirocin was superior to ebselen in reducing MRSA burden in infected PUs both in obese (98.7% reduction) and diabetic (99.3% reduction) mice. Ebselen's antibacterial activity was negatively impacted as the bacterial inoculum was increased from 10(5) CFU/mL to 10(7) CFU/mL. These results suggest that a higher dose of ebselen, or a longer course of treatment, may be needed to achieve a similar effect as mupirocin in topically treating MRSA-infected pressure ulcers.
2021-05-13T12:03:58Z
2021-05-13T12:03:58Z
2021-05-13T12:03:58Z
2021-02-22
Article - Refereed
1932-6203
e0247508
http://hdl.handle.net/10919/103260
https://doi.org/10.1371/journal.pone.0247508
16
2
33617589
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/1023002023-11-29T19:08:34Zcom_10919_78629com_10919_78628com_10919_5540com_10919_24259com_10919_5559col_10919_78791col_10919_71752col_10919_24342
Abrogation of atypical neurogenesis and vascular-derived EphA4 prevents repeated mild TBI-induced learning and memory impairments
Greer, Kisha
Gudenschwager-Basso, Erwin K.
Kelly, Colin
Cash, Alison
Kowalski, Elizabeth A.
Cerna, Steven
Ocampo, Collin Tanchanco
Wang, Xia
Theus, Michelle H.
Biomedical Sciences and Pathobiology
Brain injury resulting from repeated mild traumatic insult is associated with cognitive dysfunction and other chronic co-morbidities. The current study tested the effects of aberrant neurogenesis in a mouse model of repeated mild traumatic brain injury (rmTBI). Using Barnes Maze analysis, we found a significant reduction in spatial learning and memory at 24 days post-rmTBI compared to repeated sham (rSham) injury. Cell fate analysis showed a greater number of BrdU-labeled cells which co-expressed Prox-1 in the DG of rmTBI-injured mice which coincided with enhanced cFos expression for neuronal activity. We then selectively ablated dividing neural progenitor cells using a 7-day continuous infusion of Ara-C prior to rSham or rmTBI. This resulted in attenuation of cFos and BrdU-labeled cell changes and prevented associated learning and memory deficits. We further showed this phenotype was ameliorated in EphA4f.(/f)/Tie2-Cre knockout compared to EphA4f.(/f) wild type mice, which coincided with altered mRNA transcript levels of MCP-1, Cx43 and TGF beta. These findings demonstrate that cognitive decline is associated with an increased presence of immature neurons and gene expression changes in the DG following rmTBI. Our data also suggests that vascular EphA4-mediated neurogenic remodeling adversely affects learning and memory behavior in response to repeated insult.
2021-02-08T15:46:23Z
2021-02-08T15:46:23Z
2021-02-08T15:46:23Z
2020-09-21
Article - Refereed
2045-2322
15374
http://hdl.handle.net/10919/102300
https://doi.org/10.1038/s41598-020-72380-1
10
1
32958852
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/648302023-12-19T13:34:26Zcom_10919_5540com_10919_24259com_10919_5559col_10919_71752col_10919_24342
Toll-Like Receptor Responses to Peste des petits ruminants Virus in Goats and Water Buffalo
Dhanasekaran, Sakthivel
Biswas, Moanaro
Vignesh, Ambothi R.
Ramya, R.
Raj, Gopal Dhinakar
Tirumurugaan, Krishnaswamy G.
Raja, Angamuthu
Kataria, Ranjit S.
Parida, Satya
Elankumaran, Subbiah
Hegde, Nagendra
Goats
Cytokines
Viral replication
Gene expression
Viral gene expression
Sheep
Toll-like receptors
Veterinary disease
Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep and goats, caused by the Peste des petits ruminants virus (PPRV). Differences in susceptibility to goat plague among different breeds and water buffalo exist. The host innate immune system discriminates between pathogen associated molecular patterns and self antigens through surveillance receptors known as Toll like receptors (TLR). We investigated the role of TLR and cytokines in differential susceptibility of goat breeds and water buffalo to PPRV. We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signaling molecules correlation with susceptibility vs resistance. Naturally susceptible goat breeds, Barbari and Tellichery, had dampened innate immune responses to PPRV and increased viral loads with lower basal expression levels of TLR 3/7. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viral loads in infected PBMC. Water buffalo produced higher levels of interferon (IFN) α in comparison with goats at transcriptional and translational levels. Pre-treatment of Vero cells with human IFNα resulted in reduction of PPRV replication, confirming the role of IFNα in limiting PPRV replication. Treatment with IRS66, a TLR7 antagonist, resulted in the reduction of IFNα levels, with increased PPRV replication confirming the role of TLR7. Single nucleotide polymorphism analysis of TLR7 of these goat breeds did not show any marked nucleotide differences that might account for susceptibility vs resistance to PPRV. Analyzing other host genetic factors might provide further insights on susceptibility to PPRV and genetic polymorphisms in the host.
2016-02-16T08:03:31Z
2016-02-16T08:03:31Z
2016-02-16T08:03:31Z
2014-11-04
Article - Refereed
Dhanasekaran S, Biswas M, Vignesh AR, Ramya R, Raj GD, et al. (2014) Toll-Like Receptor Responses to Peste des petits ruminants Virus in Goats and Water Buffalo. PLoS ONE 9(11): e111609. doi:10.1371/journal.pone.0111609
1932-6203
http://hdl.handle.net/10919/64830
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111609
https://doi.org/10.1371/journal.pone.0111609
9
11
en
http://creativecommons.org/licenses/by/4.0/
Dhanasekaran, Sakthivel
Biswas, Moanaro
Vignesh, Ambothi R.
Ramya, R.
Raj, Gopal Dhinakar
Tirumurugaan, Krishnaswamy G.
Raja, Angamuthu
Kataria, Ranjit S.
Parida, Satya
Subbiah, Elankumaran
Creative Commons Attribution 4.0 International
Public Library of Science
oai:vtechworks.lib.vt.edu:10919/1114192022-08-03T07:12:40Zcom_10919_78629com_10919_78628com_10919_24259com_10919_5559col_10919_78630col_10919_24342
Advanced sequencing approaches detected insertions of viral and human origin in the viral genome of chronic hepatitis E virus patients
Papp, C-Patrick
Biedermann, Paula
Harms, Dominik
Wang, Bo
Kebelmann, Marianne
Choi, Mira
Helmuth, Johannes
Corman, Victor M.
Thuermer, Andrea
Altmann, Britta
Klink, Patrycja
Hofmann, Joerg
Bock, C-Thomas
ribavirin treatment failure
polyproline region
mutations
infection
england
growth
The awareness of hepatitis E virus (HEV) increased significantly in the last decade due to its unexpectedly high prevalence in high-income countries. There, infections with HEV-genotype 3 (HEV-3) are predominant which can progress to chronicity in immunocompromised individuals. Persistent infection and antiviral therapy can select HEV-3 variants; however, the spectrum and occurrence of HEV-3 variants is underreported. To gain in-depth insights into the viral population and to perform detailed characterization of viral genomes, we used a new approach combining long-range PCR with next-generation and third-generation sequencing which allowed near full-length sequencing of HEV-3 genomes. Furthermore, we developed a targeted ultra-deep sequencing approach to assess the dynamics of clinically relevant mutations in the RdRp-region and to detect insertions in the HVR-domain in the HEV genomes. Using this new approach, we not only identified several insertions of human (AHNAK, RPL18) and viral origin (RdRp-derived) in the HVR-region isolated from an exemplary sample but detected a variant containing two different insertions simultaneously (AHNAK- and RdRp-derived). This finding is the first HEV-variant recognized as such showing various insertions in the HVR-domain. Thus, this molecular approach will add incrementally to our current knowledge of the HEV-genome organization and pathogenesis in chronic hepatitis E.
2022-08-02T13:08:38Z
2022-08-02T13:08:38Z
2022-08-02T13:08:38Z
2022-02-02
Article - Refereed
2045-2322
1720
http://hdl.handle.net/10919/111419
https://doi.org/10.1038/s41598-022-05706-w
12
1
35110582
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Nature Portfolio
oai:vtechworks.lib.vt.edu:10919/1119322023-11-29T19:08:40Zcom_10919_5com_10919_25799com_10919_5540com_10919_24259com_10919_5559com_10919_91912com_10919_23198col_10919_70873col_10919_71752col_10919_24342col_10919_91916
EGR2 Deletion Suppresses Anti-DsDNA Autoantibody and IL-17 Production in Autoimmune-Prone B6/lpr Mice: A Differential Immune Regulatory Role of EGR2 in B6/lpr Versus Normal B6 Mice
Dai, Rujuan
Wang, Zhuang
Heid, Bettina
Eden, Kristin
Reilly, Christopher M.
Ahmed, S. Ansar
EGR2
IL-17
anti-dsDNA autoantibody
double negative T cell
murine model
plasma cell
Autoimmune Disease
Lupus
2 Aetiology
2.1 Biological and endogenous factors
Inflammatory and immune system
Previous studies have reported that deletion of the transcription factor, early growth response protein 2 (EGR2), in normal C57BL/6 (B6) resulted in the development of lupus-like autoimmune disease. However, increased EGR2 expression has been noted in human and murine lupus, which challenges the notion of the autoimmune suppressive role of EGR2 in B6 mice. In this study, we derived both conditional EGR2-/-B6/lpr and EGR2-/-B6 mice to elucidate the immune and autoimmune regulatory roles of EGR2 in autoinflammation (B6/lpr) versus physiologically normal (B6) conditions. We found that conditional EGR2 deletion increased spleen weight, enhanced T cell activation and IFNγ production, and promoted germinal center B cells and LAG3+ regulatory T cells development in both B6/lpr and B6 mice. Nevertheless, EGR2 deletion also showed strikingly differential effects in these two strains on T lymphocyte subsets profile, Foxp3+ Tregs and plasma cell differentiation, anti-dsDNA autoantibodies and immunoglobulins production, and on the induction of IL-17 in in vitro activated splenocytes. Specifically, EGR2 deletion in B6/lpr mice significantly decreased serum levels of anti-dsDNA autoantibodies, total IgG, IgM, IgG1, and IgG2a with reduced plasma cells differentiation. Furthermore, EGR2 deletion in B6/lpr mice had no obvious effect on IgG immunocomplex deposition, medium caliber vessel, and glomeruli inflammation but increased complement C3 immunocomplex deposition and large caliber vessel inflammation in the kidneys. Importantly, we demonstrated that EGR2 deletion in B6/lpr mice significantly reduced pathogenic CD4-CD8-CD3+B220+ double negative T cells, which correlated with the reduced anti-dsDNA autoantibodies in serum and decreased IL-17 production in splenocytes of EGR2-/-B6/lpr mice. Together, our data strongly suggest that the role of EGR2 is complex. The immunoregulatory role of EGR2 varies at normal or autoinflammation conditions and should not be generalized in differential experimental settings.
2022-09-20T16:39:36Z
2022-09-20T16:39:36Z
2022-09-20T16:39:36Z
2022-06-15
Article - Refereed
1664-3224
http://hdl.handle.net/10919/111932
https://doi.org/10.3389/fimmu.2022.917866
13
35784356
1664-3224
en
https://www.ncbi.nlm.nih.gov/pubmed/35784356
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Frontiers
oai:vtechworks.lib.vt.edu:10919/986012023-11-29T19:08:41Zcom_10919_8195com_10919_25799com_10919_5540com_10919_24259com_10919_5559col_10919_78882col_10919_71752col_10919_24342
Hepatitis E Virus Seroprevalence and Associated Risk Factors in Apparently Healthy Individuals from Osun State, Nigeria
Osundare, Folakemi Abiodun
Klink, Patrycja
Majer, Catharina
Akanbi, Olusola Aanuoluwapo
Wang, Bo
Faber, Mirko
Harms, Dominik
Bock, C.-Thomas
Opaleye, Oladele Oluyinka
hepatitis E virus
seroprevalence
ELISA
PCR
risk factors
Hepatitis E virus (HEV) infection is a major public health concern in low-income countries, yet incidence and prevalence estimates are often lacking. Serum (<i>n</i> = 653) and faecal (<i>n</i> = 150) samples were collected from apparently healthy individuals using convenience sampling technique in six communities (Ore, Oke-Osun, Osogbo, Ede, Esa-Odo, and Iperindo) from Osun State, Nigeria. Serum samples were analysed for total anti-HEV IgG/IgM and anti-HEV IgM using commercially available HEV ELISA kits. Total anti-HEV positive serum and all stool samples were analysed for HEV RNA by RT-PCR. Overall, 15.0% (<i>n</i> = 98/653) and 3.8% (<i>n</i> = 25/653) of the serum samples were positive for anti-HEV total and IgM antibodies, respectively. Total anti-HEV and IgM in Ore, Oke-Osun, Osogbo, Ede, Esa-Odo, and Iperindo was 21.0% (<i>n</i> = 13/62) and 3.2% (<i>n</i> = 2/62), 19.4% (<i>n</i> = 20/103) and 6.8% (<i>n</i> = 7/103), 11.4% (<i>n</i> = 12/105) and 2.9% (<i>n</i> = 3/105), 8.0% (<i>n</i> = 16/199) and 1.5% (<i>n</i> = 3/199), 22.0% (<i>n</i> = 22/100) and 10.0% (<i>n</i> = 10/100), and 17.9% (<i>n</i> = 15/84) and 0.0% (<i>n</i> = 0/84), respectively. All samples (stool and serum) were HEV RNA negative. Anti-HEV seroprevalence was associated with rural location, increasing age, alcohol consumption, and rearing of animals. This study demonstrated a high anti-HEV seroprevalence in Osun State, indicating the need to implement surveillance and asses the hepatitis E burden in Nigeria.
2020-05-29T12:00:17Z
2020-05-29T12:00:17Z
2020-05-29T12:00:17Z
2020-05-20
Article - Refereed
Osundare, F.A.; Klink, P.; Majer, C.; Akanbi, O.A.; Wang, B.; Faber, M.; Harms, D.; Bock, C.-T.; Opaleye, O.O. Hepatitis E Virus Seroprevalence and Associated Risk Factors in Apparently Healthy Individuals from Osun State, Nigeria. Pathogens 2020, 9, 392.
http://hdl.handle.net/10919/98601
https://doi.org/10.3390/pathogens9050392
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/1115622022-08-20T07:19:14Zcom_10919_24259com_10919_5559com_10919_91913com_10919_23198col_10919_24342col_10919_91914
Editorial: RNA Localization and Localized Translation in Neurons
Farris, Shannon
Hacisuleyman, Ezgi
Donlin-Asp, Paul
Cioni, Jean-Michel
RNA localization
local translation
RNA transport
neuron
axon
dendrite
2022-08-19T12:58:57Z
2022-08-19T12:58:57Z
2022-08-19T12:58:57Z
2022-01-12
Article
1662-5145
831038
http://hdl.handle.net/10919/111562
https://doi.org/10.3389/fnint.2021.831038
15
35095435
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
Frontiers
oai:vtechworks.lib.vt.edu:10919/1031692022-02-28T15:10:54Zcom_10919_78629com_10919_78628com_10919_24259com_10919_5559col_10919_78630col_10919_24342
N-(1,3,4-Oxadiazol-2-yl)Benzamides as Antibacterial Agents against Neisseria gonorrhoeae
Naclerio, George A.
Abutaleb, Nader S.
Alhashimi, Marwa
Seleem, Mohamed N.
Sintim, Herman O.
Biomedical Sciences and Pathobiology
Neisseria gonorrhoeae
1,3,4-oxadiazole
antibiotic
antimicrobial resistance
The Centers for Disease Control and Prevention (CDC) recognizes Neisseria gonorrhoeae as an urgent-threat Gram-negative bacterial pathogen. Additionally, resistance to frontline treatment (dual therapy with azithromycin and ceftriaxone) has led to the emergence of multidrug-resistant N. gonorrhoeae, which has caused a global health crisis. The drug pipeline for N. gonorrhoeae has been severely lacking as new antibacterial agents have not been approved by the FDA in the last twenty years. Thus, there is a need for new chemical entities active against drug-resistant N. gonorrhoeae. Trifluoromethylsulfonyl (SO2CF3), trifluoromethylthio (SCF3), and pentafluorosulfanyl (SF5) containing N-(1,3,4-oxadiazol-2-yl)benzamides are novel compounds with potent activities against Gram-positive bacterial pathogens. Here, we report the discovery of new N-(1,3,4-oxadiazol-2-yl)benzamides (HSGN-237 and -238) with highly potent activity against N. gonorrhoeae. Additionally, these new compounds were shown to have activity against clinically important Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Listeria monocytogenes (minimum inhibitory concentrations (MICs) as low as 0.25 mu g/mL). Both compounds were highly tolerable to human cell lines. Moreover, HSGN-238 showed an outstanding ability to permeate across the gastrointestinal tract, indicating it would have a high systemic absorption if used as an anti-gonococcal therapeutic.
2021-04-29T17:09:17Z
2021-04-29T17:09:17Z
2021-04-29T17:09:17Z
2021-03
Article - Refereed
2427
http://hdl.handle.net/10919/103169
https://doi.org/10.3390/ijms22052427
22
5
33671065
1422-0067
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
oai:vtechworks.lib.vt.edu:10919/751922023-12-19T13:34:26Zcom_10919_5540com_10919_24259com_10919_5559col_10919_71752col_10919_24342
The Parity-Associated Microenvironmental Niche in the Omental Fat Band Is Refractory to Ovarian Cancer Metastasis
Cohen, Courtney A.
Shea, Amanda A.
Heffron, C. Lynn
Schmelz, Eva M.
Roberts, Paul C.
Ovarian cancer is an insidious and aggressive disease of older women, typically undiscovered prior to peritoneal metastasis due to its asymptomatic nature and lack of early detection tools. Epidemiological studies suggest that child-bearing (parity) is associated with decreased ovarian cancer risk, although the molecular mechanisms responsible for this phenomenon have not been delineated. Ovarian cancer preferentially metastasizes to the omental fat band (OFB), a secondary lymphoid organ that aids in filtration of the peritoneal serous fluid (PSF) and helps combat peritoneal infections. In the present study we assessed how parity and age impact the immune compositional profile in the OFB of mice, both in the homeostatic state and as a consequence of peritoneal implantation of ovarian cancer. Using fluorescence-activated cell sorting analysis and quantitative realtime PCR, we found that parity was associated with a significant reduction in omental monocytic subsets and B1-B lymphocytes, correlating with reduced homeostatic expression levels of key chemoattractants and polarization factors (Ccl1, Ccl2, Arg1, Cxcl13). Of note, parous animals exhibited significantly reduced tumor burden following intraperitoneal implantation compared to nulliparous animals. This was associated with a reduction in tumor-associated neutrophils and macrophages, as well as in the expression levels of their chemoattractants (Cxcl1, Cxcl5) in the OFB and PSF. These findings define a pre-existing "parity-associated microenvironmental niche" in the OFB that is refractory to metastatic tumor seeding and outgrowth. Future studies designed to manipulate this niche may provide a novel means to mitigate peritoneal dissemination of ovarian cancer.
2017-02-27T20:46:05Z
2017-02-27T20:46:05Z
2017-02-27T20:46:05Z
2013-09-10
Article - Refereed
http://hdl.handle.net/10919/75192
https://doi.org/10.1158/1940-6207.CAPR-13-0227
6
11
en
http://rightsstatements.org/vocab/InC/1.0/
In Copyright
American Association for Cancer Research
oai:vtechworks.lib.vt.edu:10919/1109012023-08-30T19:29:23Zcom_10919_8195com_10919_25799com_10919_24216com_10919_5539com_10919_24259com_10919_5559com_10919_23765com_10919_24263col_10919_78882col_10919_24286col_10919_24342col_10919_24353col_10919_24345
High-Frequency Irreversible Electroporation (H-FIRE) Induced Blood-Brain Barrier Disruption Is Mediated by Cytoskeletal Remodeling and Changes in Tight Junction Protein Regulation
Partridge, Brittanie R.
Kani, Yukitaka
Lorenzo, Melvin F.
Campelo, Sabrina N.
Allen, Irving C.
Hinckley, Jonathan
Hsu, Fang-Chi
Verbridge, Scott S.
Robertson, John L.
Davalos, Rafael V.
Rossmeisl, John H.
Glioblastoma is the deadliest malignant brain tumor. Its location behind the blood–brain barrier (BBB) presents a therapeutic challenge by preventing effective delivery of most chemotherapeutics. H-FIRE is a novel tumor ablation method that transiently disrupts the BBB through currently unknown mechanisms. We hypothesized that H-FIRE mediated BBB disruption (BBBD) occurs via cytoskeletal remodeling and alterations in tight junction (TJ) protein regulation. Intracranial H-FIRE was delivered to Fischer rats prior to sacrifice at 1-, 24-, 48-, 72-, and 96 h post-treatment. Cytoskeletal proteins and native and ubiquitinated TJ proteins (TJP) were evaluated using immunoprecipitation, Western blotting, and gene-expression arrays on treated and sham control brain lysates. Cytoskeletal and TJ protein expression were further evaluated with immunofluorescent microscopy. A decrease in the F/G-actin ratio, decreased TJP concentrations, and increased ubiquitination of TJP were observed 1–48 h post-H-FIRE compared to sham controls. By 72–96 h, cytoskeletal and TJP expression recovered to pretreatment levels, temporally corresponding with increased claudin-5 and zonula occludens-1 gene expression. Ingenuity pathway analysis revealed significant dysregulation of claudin genes, centered around claudin-6 in H-FIRE treated rats. In conclusion, H-FIRE is capable of permeating the BBB in a spatiotemporal manner via cytoskeletal-mediated TJP modulation. This minimally invasive technology presents with applications for localized and long-lived enhanced intracranial drug delivery.
2022-06-23T18:49:30Z
2022-06-23T18:49:30Z
2022-06-23T18:49:30Z
2022-06-11
Article - Refereed
Partridge, B.R.; Kani, Y.; Lorenzo, M.F.; Campelo, S.N.; Allen, I.C.; Hinckley, J.; Hsu, F.-C.; Verbridge, S.S.; Robertson, J.L.; Davalos, R.V.; Rossmeisl, J.H. High-Frequency Irreversible Electroporation (H-FIRE) Induced Blood-Brain Barrier Disruption Is Mediated by Cytoskeletal Remodeling and Changes in Tight Junction Protein Regulation. Biomedicines 2022, 10, 1384.
http://hdl.handle.net/10919/110901
https://doi.org/10.3390/biomedicines10061384
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
MDPI
oai:vtechworks.lib.vt.edu:10919/862182023-12-19T13:34:26Zcom_10919_78629com_10919_78628com_10919_24259com_10919_5559col_10919_78630col_10919_24342
Expanding Host Range and Cross-Species Infection of Hepatitis E Virus
Meng, Xiang-Jin
zoonotic transmission
family hepeviridae
swine
prevalence
liver
humans
risk
food
Hepatitis E is an important public health disease [1]. Although the mortality rate is less than 1% in the general population, it can reach up to 25% in infected pregnant women. According to the World Health Organization, each year an estimated 20 million infections occur worldwide resulting in >3 million symptomatic cases and 56,600 hepatitis E-related deaths (http://www.who.int/mediacentre/factsheets/fs280/en/). Large explosive waterborne outbreaks of hepatitis E are generally seen in developing countries with poor sanitation conditions, whereas in industrialized countries, sporadic and cluster cases of hepatitis E have been reported. Hepatitis E is a self-limiting acute disease that normally does not go into chronicity. However, recently, chronic hepatitis E has become a significant clinical problem in immunocompromised individuals such as organ transplant recipients [2]. The discovery of animal strains of hepatitis E virus (HEV) [3] that infect across species barriers revolutionizes the way we used to think about this important disease. Hepatitis E is now recognized as a zoonotic disease, and animal reservoirs exist [4]. Herein, I briefly discuss the ever-expanding host ranges, cross-species infection, zoonotic risk, and food safety of HEV.
2018-12-04T18:42:14Z
2018-12-04T18:42:14Z
2018-12-04T18:42:14Z
2016-08-04
Article - Refereed
1553-7366
e1005695
http://hdl.handle.net/10919/86218
https://doi.org/10.1371/journal.ppat.1005695
12
8
27490119
1553-7374
en
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International
PLOS
qdc///col_10919_24342/100