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- 5th International Symposium on Focused UltrasoundAbounader, Roger; Abraham, Christopher; Adema, Gosse; Agrawal, Punit; Airan, Raag; Aleman, Dionne; Alexander, Phillip; Alkins, Ryan; Alnazeer, Moez; Altman, Michael; Aly, Amirah; Amaral, Joao G.; Amrahli, Maral; Amraoui, Sana; Andarawewa, Kumari; Andriyakhina, Yulia; Angstadt, Mary; Ankou, Bénédicte; Arias, Ana C.; Arvanitis, Costas; Asadnia, Kiana; Aubert, Isabelle; Aubry, Jean-Francois; Aubry, Jean-Francois; Aurup, Christian; Bader, Kenneth; Badr, Lena; Baek, Hongchae; Barbato, Gaetano; Beccaria, Kevin; Bellorofonte, Carlo; Benson, Lee; Bernus, Olivier; Berriet, Rémi; Bertolina, Jim; Beskin, Viktoriya; Bessière, Francis; Bethune, Allison; Bezzi, Mario; Bond, Aaron; Bonomo, Guido; Borowsky, Alexander; Borys, Nicolas; Böttcher, Joachim; Bouley, Donna; Bour, Pierre; Bourekas, Eric; Brenin, David; Brokman, Omer; Brosh, Inbar; Buckner, Andrew; Bullock, Timothy; Cafarelli, Andrea; Cahill, Jessica; Camarena, Francisco; Camelo-Piragua, Sandra; Campbell, Benjamin; Campbell, Fiona; Cannata, Jon; Canney, Michael; Carlson, Roy; Carneiro, Antonio; Carpentier, Alexandre; Catheline, Stefan; Cavin, Ian; Cesana, Claudio; Chabok, Hamid R.; Chamanara, Marzieh; Chang, Jin H.; Chang, Won S.; Changizi, Barbara; Chapelon, Jean Y.; Chaplin, Vandiver; Chapman, Martin; Chaudhary, Neeraj; Chaussy, Christian; Chen, Cherry; Chen, Johnny; Chen, Wohsing; Chen, Xiaoming; Chevalier, Philippe; Chiou, George; Chisholm, Alexander; Christofferson, Ivy; Chung, Hyun H.; Ciuti, Gastone; Clement, Gregory; Cooper, Mark; Corea, Joseph; Corso, Cristiano; Cosman, Josh; Coughlin, Dezba; Crake, Calum; Cunitz, Bryan; Curiel, Laura; Curley, Colleen T.; Czarnota, Gregory; Dababou, Susan; Dallapiazza, Robert; de Bever, Joshua; de Jager, Bram; de Ruiter, Joost; de Senneville, Baudouin D.; Deckers, Roel; Delattre, Jean-Yves; den Brok, Martijn; Dhanaliwala, Ali; Diodato, Alessandro; Dixon, Adam; Donner, Elizabeth; Downs, Matthew; Du, Zhongmin; Dubois, Rémi; Dupre, Aurelien; Eikelenboom, Dylan; Elias, W. J.; Ellens, Nicholas; Endre, Ruby; Eran, Ayelet; Erasmus, Hans-Peter; Everstine, Ashli; Farahani, Keyvan; Farrer, Alexis; Farry, Justin; Federau, Christian; Feng, Xue; Ferrer, Cyril; Ferrera, Vincent; Fishman, Paul; Foley, Jessica; Frenkel, Victor; Fütterer, Jurgen; Gach, H. M.; Gandhi, Dheeraj; Gertner, Michael; Goldsher, Dorit; Gorgone, Alessandro; Greillier, Paul; Griesenauer, Rebekah; Grissom, William; Grondin, Julien; Guha, Chandan; Gulati, Amitabh; Gullapalli, Rao; Guo, Sijia; Gupta, Samit; Gurm, Hitinder; Gwinn, Ryder; Hadley, Rock; Haïssaguerre, Michel; Hammoud, Dima; Hananel, Arik; Hargrove, Amelia; Hatch, Robert; Haworth, Kevin; Hazan, Eilon; He, Ye; Heemels, Maurice; Heerschap, Arend; Hilas, Elaine; Hoang-Xuan, Khe; Hocini, Mélèze; Hodaie, Mojgan; Hofmann, Denis; Holland, Christy; Hoogenboom, Martijn; Hopyan, Sevan; Hossack, John; Houdouin, Alexandre; Hsu, Po-Hung; Hu, Jim; Hurwitz, Mark; Huss, Diane; Hwang, Chang-il; Hwang, Joo H.; Idbaih, Ahmed; Ikeuchi, Masahiko; Ingham, Elizabeth; Ives, Kimberly; Izumi, Masashi; Jackson-Lewis, Vernice; Janát-Amsbury, Margit; Jang, Kee W.; Jedruszczuk, Kathleen; Jiménez-Gambín, Sergio; Jiménez, Noé; Johnson, Sara; Jonathan, Sumeeth; Joy, Joyce; Jung, Hyun H.; Jung, Na Y.; Kahn, Itamar; Kamimura, Hermes; Kamrava, Seyed K.; Kang, Jeeun; Kang, Kook J.; Kang, Soo Y.; Kao, Yi-tzu; Katti, Prateek; Kawasaki, Motohiro; Kaye, Elena; Keupp, Jochen; Kim, AeRang; Kim, Harry; Kim, Hyun-Chul; Kim, Hyuncheol; Kim, Hyungmin; Kim, Min S.; Kim, Namho; Kiyasu, Katsuhito; Kneepkens, Esther; Knopp, Michael; Kobus, Thiele; Koral, Korgun; Kreider, Wayne; Krishna, Vibhor; Krug, Roland; Krupa, Steve; Kuo, Chia-Chun; Kwiecinski, Wojciech; Lacoste, Romain; Lam, Heather; Lamberti-Pasculli, Maria; Lang, Brian; Larner, James; Larrabee, Zachary; Leach, J. K.; LeBlang, Suzanne; Leclercq, Delphine; Lee, Hak J.; Lee, Jong-Hwan; Lehericy, Stéphane; Leighton, Wan; Leung, Steven; Lewis, Bobbi; Lewis, Matthew; Li, Dawei; Linn, Sabine; Lipsman, Nir; Liu, Hao-Li; Liu, Jingfei; Lopes, M. B.; Lotz, Jeff; Lu, Xin; Lundt, Jonathan; Luo, Xi; Lustgarten, Lior; Lustig, Micheal; Macoskey, Jonathan; Madore, Bruno; Maev, Roman; Magat, Julie; Maimbourg, Guillaume; Maimon, Noam; Mainprize, Todd; Malayer, Jerry; Maples, Danny; Marquet, Fabrice; Marrocchio, Cristina; Marx, Mike; Mastorakos, Panagiotis; Mauri, Giovanni; McLean, Hailey; McMichael, John; Mead, Brian P.; Melodelima, David; Melot-Dusseau, Sandrine; Menciassi, Arianna; Merrill, Robb; Meyer, Joshua; Midiri, Massimo; Miga, Michael; Migliore, Ilaria G.; Miller, Eric; Minalga, Emilee; Moon, Hyungwon; Moore, David; Mourad, Pierre; Mouratidis, Petros; Mueller, Michael; Mugler, John; Muller, Sébastien; Namba, Hirofumi; Naor, Omer; Nassar, Maria; Nazai, Navid; Negron, Karina; Negussie, Ayele; Nguyen, Thai-Son; Nicolay, Klaas; Nikolaeva, Anastasia V.; Oetgen, Matthew; Olive, Kenneth; Olumolade, Oluyemi; Orsi, Franco; Owens, Gabe; Ozilgen, Arda; Padegimas, Linas; Palermo, Carmine; Pan, Chia-Hsin; Pandey, Aditya; Papadakis, Georgios; Park, Chang K.; Park, Sang M.; Parker, Jonathon; Parvizi, Mohammad H.; Pascal-Tenorio, Aurea; Patel, Janish; Patz, Sam; Payen, Thomas; Perich, Eloi; Pernot, Mathieu; Perol, David; Perry, James; Pillarisetty, Venu; Pioche, Mathieu; Pizzuto, Matthew; Plaksin, Michael; Plata, Juan; Price, Karl; Prince, Jessica; Przedborski, Serge; Quinones-Hinojosa, Alfredo; Ramachandran, Akhilesh; Ranjan, Ashish; Ravikumar, Vinod; Reichenbach, Juergen; Repasky, Elizabeth; Rezai, Ali; Ritter, Philippe; Rivoire, Michel; Rochman, Carrie; Rosenberg, Jarrett; Rosnitskiy, Pavel B.; Ruiz, Antonio; Sahgal, Arjun; Samiotaki, Gesthimani; Sanghvi, Narendra; Santin, Mathieu D.; Santos, Domiciano; Sasaki, Noboru; Sastra, Steve; Schade, George; Schall, Jeffrey; Schlesinger, Ilana; Schmitt, Paul; Schwaab, Julia; Scionti, Stephen; Scipione, Roberto; Scoarughi, Gian L.; Scott, Serena; Sebeke, Lukas; Seifabadi, Reza; Seo, Jai; Sesenoglu-Laird, Ozge; Shah, Binit; Shahriari, Kian; Shaikh, Sumbul; Shea, Jill; Shi, Jiaqi; Shim, Jenny; Shinkov, Alexander; Shuman, Jillian; Silvestrini, Matthew; Sim, Changbeom; Sin, Vivian; Sinai, Alon; Singh, Manoj; Sinilshchikov, Ilya; Skalina, Karin; Slingluff, Craig; So, Po-Wah; Solomon, Stephen; Son, Keon H.; Sperling, Scott; Stein, Ruben; Stein, Sherman; Stevens, Aaron; Stimec, Jennifer; Storm, Gert; Straube, William; Suelmann, Britt; Sutton, Jonathan; Svedin, Bryant; Takemasa, Ryuichi; Takiguchi, Mitsuyoshi; Tam, Emily; Tan, Jeremy; Tang, Xinyan; Tanter, Mickael; Tebebi, Pamela; Tehrani, Seruz; Temple, Michael; Teofilovic, Dejan; ter Haar, Gail; Terzi, Marina E.; Thueroff, Stefan; Timbie, Kelsie; Tognarelli, Selene; Tretbar, Steffen; Trudeau, Maureen; Tsai, Yi-Chieh; Tsysar, Sergey A.; Tucci, Samantha; Tuveson, David; Ushida, Takahiro; Vaessen, Paul; Vaillant, Fanny; Van Arsdell, Glen; van Breugel, Johanna; Van der Jeugd, Anneke; Van der Jeugd, Anneke; Van der Wall, Elsken; van Diest, Paul; van Stralen, Marijn; Varano, Gianluca; Velat, Manuela; Vidal-Jove, Joan; Vigna, Paolo D.; Vignot, Alexandre; Vincenot, Jeremy; Vykhodtseva, Natalia; Wang, Bin; Wang, Han; Wang, Kevin; Wang, Qi; Wang, Qingguo; Wang, Shengping; Wang, Yak-Nam; Wang, Zhaorui; Wardlow, Rachel; Warren, Amy; Waszczak, Barbara; Watson, Katherine; Webb, Taylor; Wei-Bin, Shen; Wei, Kuo-Chen; Weiss, Steffen; Weissler, Yoni; Werner, Beat; Wesseling, Pieter; Williams, Noelle; Wilson, Emmanuel; Wintermark, Max; Witkamp, Arjen; Wong, Carlos; Wu, Jing-Fu; Wydra, Adrian; Xu, Alexis; Xu, Doudou; Xu, Su; Yang, Georgiana; Yang, Nai-Yi; Yao, Chen; Yarowsky, Paul; Ye, Patrick P.; Yuldashev, Petr; Zaaroor, Menashe; Zachiu, Cornel; Zahos, Peter; Zangos, Stephan; Zhang, Dandan; Zhang, Hua; Zhang, Jimin; Zhang, Junhai; Zhang, Xi; Zhao, Li; Zhong, Pei; Zhuo, Jiachen; Zidowitz, Stephan; Zinke, Wolf; Zorgani, Ali (2016-11-21)
- Aberrant placental immune parameters in the feline immunodeficiency virus (FIV)-infected cat suggest virus-induced changes in T cell functionChumbley, Lyndon B.; Boudreaux, Crystal E.; Coats, Karen S. (2013-07-19)Background Immune activity during pregnancy must be tightly regulated to ensure successful pregnancy. This regulation includes the suppression of inflammatory activity that could target the semi-allogeneic fetus. Tregs are immunosuppressive; Th17 cells are pro-inflammatory. A precise balance in the two cell populations is critical to pregnancy maintenance, while dysregulation in this balance accompanies compromised pregnancy in humans and mice. FIV is known to target Tregs preferentially in the infected cat. Therefore, it may be hypothesized that FIV infection alters the placental Treg/Th17 cell balance resulting in aberrant immunomodulator expression by these cells and consequent pregnancy perturbation. Methods RNA was purified from random sections of whole placental tissues collected from both uninfected and FIV-infected queens at early pregnancy, including tissues from viable and nonviable fetuses. Real time qPCR was performed to quantify expression of intranuclear markers of Tregs (FoxP3) and Th17 cells (RORΩ); cytokine products of Tregs (IL-10 and TGF-β), Th17 cells (IL-2, IL-6, and IL-17a), and macrophages (IL-1β); and the FIV gag gene. Pairwise comparisons were made to evaluate coexpression patterns between the cytokines and between the cytokines and the virus. Results Both FoxP3 and RORΩ were reduced in placentas of infected animals. Neither infection status nor fetal viability affected placental expression of IL-1β. However, fetal nonviability was associated with reduced levels of all other cytokines. Infection and fetal nonviability impacted coexpression of various cytokine pairs. No obvious bias toward Treg or Th17 cells was observed. Conclusions FIV infection coupled with fetal nonviability alters expression patterns of T cell cytokines. These data suggest that functionally altered placental T cell leukocyte populations may occur in the infected queen and possibly contribute to fetal nonviability.
- Ablation outcome of irreversible electroporation on potato monitored by impedance spectrum under multi-electrode systemZhao, Yajun; Liu, Hongmei; Bhonsle, Suyashree P.; Wang, Yilin; Davalos, Rafael V.; Yao, Chenguo (2018-09-20)Background Irreversible electroporation (IRE) therapy relies on pulsed electric fields to non-thermally ablate cancerous tissue. Methods for evaluating IRE ablation in situ are critical to assessing treatment outcome. Analyzing changes in tissue impedance caused by electroporation has been proposed as a method for quantifying IRE ablation. In this paper, we assess the hypothesis that irreversible electroporation ablation outcome can be monitored using the impedance change measured by the electrode pairs not in use, getting more information about the ablation size in different directions. Methods Using a square four-electrode configuration, the two diagonal electrodes were used to electroporate potato tissue. Next, the impedance changes, before and after treatment, were measured from different electrode pairs and the impedance information was extracted by fitting the data to an equivalent circuit model. Finally, we correlated the change of impedance from various electrode pairs to the ablation geometry through the use of fitted functions; then these functions were used to predict the ablation size and compared to the numerical simulation results. Results The change in impedance from the electrodes used to apply pulses is larger and has higher deviation than the other electrode pairs. The ablation size and the change in resistance in the circuit model correlate with various linear functions. The coefficients of determination for the three functions are 0.8121, 0.8188 and 0.8691, respectively, showing satisfactory agreement. The functions can well predict the ablation size under different pulse numbers, and in some directions it did even better than the numerical simulation method, which used different electric field thresholds for different pulse numbers. Conclusions The relative change in tissue impedance measured from the non-energized electrodes can be used to assess ablation size during treatment with IRE according to linear functions.
- Abstracts from the 3rd Conference on Aneuploidy and Cancer: Clinical and Experimental AspectsCornish-Bowden, Athel; Rasnick, David; Heng, Henry H.; Horne, Steven; Abdallah, Batoul; Liu, Guo; Ye, Christine J.; Bloomfield, Mathew; Vincent, Mark D.; Aldaz, C. M.; Karlsson, Jenny; Valind, Anders; Jansson, Caroline; Gisselsson, David; Graves, Jennifer A. M.; Stepanenko, Aleksei A.; Andreieva, Svitlana V.; Korets, Kateryna V.; Mykytenko, Dmytro O.; Huleyuk, Nataliya L.; Baklaushev, Vladimir P.; Kovaleva, Oksana A.; Chekhonin, Vladimir P.; Vassetzky, Yegor S.; Avdieiev, Stanislav S.; Bakker, Bjorn; Taudt, Aaron S.; Belderbos, Mirjam E.; Porubsky, David; Spierings, Diana C. J.; de Jong, Tristan V.; Halsema, Nancy; Kazemier, Hinke G.; Hoekstra-Wakker, Karina; Bradley, Allan; de Bont, Eveline S. J. M.; van den Berg, Anke; Guryev, Victor; Lansdorp, Peter M.; Tatché, Maria C.; Foijer, Floris; Liehr, Thomas; Baudoin, Nicolaas C.; Nicholson, Joshua M.; Soto, Kimberly; Quintanilla, Isabel; Camps, Jordi; Cimini, Daniela; Dürrbaum, M.; Donnelly, N.; Passerini, V.; Kruse, C.; Habermann, B.; Storchová, Z.; Mandrioli, Daniele; Belpoggi, Fiorella; Silbergeld, Ellen K.; Perry, Melissa J.; Skotheim, Rolf I.; Løvf, Marthe; Johannessen, Bjarne; Hoff, Andreas M.; Zhao, Sen; SveeStrømme, Jonas M.; Sveen, Anita; Lothe, Ragnhild A.; Hehlmann, R.; Voskanyan, A.; Fabarius, A.; Böcking, Alfred; Biesterfeld, Stefan; Berynskyy, Leonid; Börgermann, Christof; Engers, Rainer; Dietz, Josef; Fritz, A.; Sehgal, N.; Vecerova, J.; Stojkovicz, B.; Ding, H.; Page, N.; Tye, C.; Bhattacharya, S.; Xu, J.; Stein, G.; Stein, J.; Berezney, R.; Gong, Xue; Grasedieck, Sarah; Swoboda, Julian; Rücker, Frank G.; Bullinger, Lars; Pollack, Jonathan R.; Roumelioti, Fani-Marlen; Chiourea, Maria; Raftopoulou, Christina; Gagos, Sarantis; Duesberg, Peter; Bloomfield, Mathew; Hwang, Sunyoung; Gustafsson, Hans T.; O’Sullivan, Ciara; Acevedo-Colina, Aracelli; Huang, Xinhe; Klose, Christian; Schevchenko, Andrej; Dickson, Robert C.; Cavaliere, Paola; Dephoure, Noah; Torres, Eduardo M.; Stampfer, Martha R.; Vrba, Lukas; LaBarge, Mark A.; Futscher, Bernard; Garbe, James C.; Trinh, Andrew L.; Zhou, Yi-Hong; Digman, Michelle (2017-06-22)
- Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in ChinaLau, Eric H. Y.; Zheng, Jiandong; Tsang, Tim K.; Liao, Qiaohong; Lewis, Bryan L.; Brownstein, John S.; Sanders, Sharon; Wong, Jessica Y.; Mekaru, Sumiko R.; Rivers, Caitlin; Wu, Peng; Jiang, Hui; Li, Yu; Yu, Jianxing; Zhang, Qian; Chang, Zhaorui; Liu, Fengfeng; Peng, Zhibin; Leung, Gabriel M.; Feng, Luzhao; Cowling, Benjamin J.; Yu, Hongjie (2014-05-28)Background Appropriate public health responses to infectious disease threats should be based on best-available evidence, which requires timely reliable data for appropriate analysis. During the early stages of epidemics, analysis of ‘line lists’ with detailed information on laboratory-confirmed cases can provide important insights into the epidemiology of a specific disease. The objective of the present study was to investigate the extent to which reliable epidemiologic inferences could be made from publicly-available epidemiologic data of human infection with influenza A(H7N9) virus. Methods We collated and compared six different line lists of laboratory-confirmed human cases of influenza A(H7N9) virus infection in the 2013 outbreak in China, including the official line list constructed by the Chinese Center for Disease Control and Prevention plus five other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of Hong Kong and FluTrackers, based on publicly-available information. We characterized clinical severity and transmissibility of the outbreak, using line lists available at specific dates to estimate epidemiologic parameters, to replicate real-time inferences on the hospitalization fatality risk, and the impact of live poultry market closure. Results Demographic information was mostly complete (less than 10% missing for all variables) in different line lists, but there were more missing data on dates of hospitalization, discharge and health status (more than 10% missing for each variable). The estimated onset to hospitalization distributions were similar (median ranged from 4.6 to 5.6 days) for all line lists. Hospital fatality risk was consistently around 20% in the early phase of the epidemic for all line lists and approached the final estimate of 35% afterwards for the official line list only. Most of the line lists estimated >90% reduction in incidence rates after live poultry market closures in Shanghai, Nanjing and Hangzhou. Conclusions We demonstrated that analysis of publicly-available data on H7N9 permitted reliable assessment of transmissibility and geographical dispersion, while assessment of clinical severity was less straightforward. Our results highlight the potential value in constructing a minimum dataset with standardized format and definition, and regular updates of patient status. Such an approach could be particularly useful for diseases that spread across multiple countries.
- Acetylcholinesterase of the sand fly, Phlebotomus papatasi (Scopoli): construction, expression and biochemical properties of the G119S orthologous mutantTemeyer, Kevin B.; Tong, Fan; Totrov, Maxim M.; Tuckow, Alexander P.; Chen, Qiao-Hong; Carlier, Paul R.; Pérez de León, Adalberto A.; Bloomquist, Jeffrey R. (2014-12-10)Background Phlebotomus papatasi vectors zoonotic cutaneous leishmaniasis. Previous expression of recombinant P. papatasi acetylcholinesterase (PpAChE1) revealed 85% amino acid sequence identity to mosquito AChE and identified synthetic carbamates that effectively inhibited PpAChE1 with improved specificity for arthropod AChEs compared to mammalian AChEs. We hypothesized that the G119S mutation causing high level resistance to organophosphate insecticides in mosquitoes may occur in PpAChE1 and may reduce sensitivity to inhibition. We report construction, expression, and biochemical properties of rPpAChE1 containing the G119S orthologous mutation. Methods Targeted mutagenesis introduced the G119S orthologous substitution in PpAChE1 cDNA. Recombinant PpAChE1 enzymes containing or lacking the G119S mutation were expressed in the baculoviral system. Biochemical assays were conducted to determine altered catalytic properties and inhibitor sensitivity resulting from the G119S substitution. A molecular homology model was constructed to examine the modeled structural interference with docking of inhibitors of different classes. Genetic tests were conducted to determine if the G119S orthologous codon existed in polymorphic form in a laboratory colony of P. papatasi. Results Recombinant PpAChE1 containing the G119S substitution exhibited altered biochemical properties, and reduced inhibition by compounds that bind to the acylation site on the enzyme (with the exception of eserine). Less resistance was directed against bivalent or peripheral site inhibitors, in good agreement with modeled inhibitor docking. Eserine appeared to be a special case capable of inhibition in the absence of covalent binding at the acylation site. Genetic tests did not detect the G119S mutation in a laboratory colony of P. papatasi but did reveal that the G119S codon existed in polymorphic form (GGA + GGC). Conclusions The finding of G119S codon polymorphism in a laboratory colony of P. papatasi suggests that a single nucleotide transversion (GGC → AGC) may readily occur, causing rapid development of resistance to organophosphate and phenyl-substituted carbamate insecticides under strong selection. Careful management of pesticide use in IPM programs is important to prevent or mitigate development and fixation of the G119S mutation in susceptible pest populations. Availability of recombinant AChEs enables identification of novel inhibitory ligands with improved efficacy and specificity for AChEs of arthropod pests.
- Acoustic differences between healthy and depressed people: a cross-situation studyWang, Jingying; Zhang, Lei; Liu, Tianli; Pan, Wei; Hu, Bin; Zhu, Tingshao (2019-10-15)Background Abnormalities in vocal expression during a depressed episode have frequently been reported in people with depression, but less is known about if these abnormalities only exist in special situations. In addition, the impacts of irrelevant demographic variables on voice were uncontrolled in previous studies. Therefore, this study compares the vocal differences between depressed and healthy people under various situations with irrelevant variables being regarded as covariates. Methods To examine whether the vocal abnormalities in people with depression only exist in special situations, this study compared the vocal differences between healthy people and patients with unipolar depression in 12 situations (speech scenarios). Positive, negative and neutral voice expressions between depressed and healthy people were compared in four tasks. Multiple analysis of covariance (MANCOVA) was used for evaluating the main effects of variable group (depressed vs. healthy) on acoustic features. The significances of acoustic features were evaluated by both statistical significance and magnitude of effect size. Results The results of multivariate analysis of covariance showed that significant differences between the two groups were observed in all 12 speech scenarios. Although significant acoustic features were not the same in different scenarios, we found that three acoustic features (loudness, MFCC5 and MFCC7) were consistently different between people with and without depression with large effect magnitude. Conclusions Vocal differences between depressed and healthy people exist in 12 scenarios. Acoustic features including loudness, MFCC5 and MFCC7 have potentials to be indicators for identifying depression via voice analysis. These findings support that depressed people’s voices include both situation-specific and cross-situational patterns of acoustic features.
- Acutely enhancing affective state and social connection following an online dance intervention during the COVID-19 social isolation crisisHumphries, Ashlee; Tasnim, Noor; Rugh, Rachel; Patrick, Morgan; Basso, Julia C. (2023-01-16)The COVID-19 pandemic has forced many throughout the world to isolate themselves from their respective communities to stop the spread of disease. Although this form of distancing can prevent the contraction of a virus, it results in social isolation and physical inactivity. Consequently, our communities have become heavily reliant on digital solutions to foster social connection and increase physical activity when forced to isolate. Dance is a multidimensional form of physical activity that includes sensory, motor, cognitive, rhythmic, creative, and social elements. Long-term, interventional studies in dance have shown positive effects on both mental and social health; however, little has been done to examine the acute effects and no studies to date have explored the relationship between the affective state and social outcomes of dance. We examined the hypothesis that online dance is associated with improvements in affective state and social connection during a time of social isolation, namely, the COVID-19 crisis. Healthy adults (age ≥ 18; n = 47) engaged in a single session of 60 min of self-selected online dance, completing a series of validated self-reported questionnaires before and after class. We found that online dance was associated with improvements in affective state as measured by increased positive affect and self-esteem and decreased negative affect and depressive symptoms. Additionally, online dance was associated with improvements in social and community connectedness. Further, we found that those who experienced the largest increases in self-esteem and decreases in negative affect demonstrated the largest gains in social connectivity. Although in-person dance classes may be optimal for formalized dance training, online dance instruction offers an accessible platform that can provide mental and social health benefits during the COVID-19 social isolation crisis. We conclude that through online dance, individuals can experience a connection between the body, mind, and community.
- ADAM: Analysis of Discrete Models of Biological Systems Using Computer AlgebraHinkelmann, Franziska; Brandon, Madison; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard C. (2011-07-20)Background Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. Results We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Conclusions Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web-based tool for several different input formats, and it makes analysis of complex models accessible to a larger community, as it is platform independent as a web-service and does not require understanding of the underlying mathematics.
- Addressing opioid misuse through community-engaged strategy development: study protocol of a randomized controlled trialZimmerman, Emily B.; Rafie, Carlin; Wenzel, Sophie G.; Hosig, Kathryn; Villani, Domenique; Dance, Jon; Lee, Samantha S. (2024-07-19)Background: Involving stakeholders in the research process facilitates collaboration, increasing understanding of factors influencing their wellbeing and motivating community action. Currently, there is a need for randomized controlled trials to evaluate the effectiveness of community-engaged research approaches for health, well-being, and engagement outcomes. In this study, we evaluate the effectiveness of both the SEED Method and a modified Delphi method in a participatory project to develop local strategies to address the opioid epidemic in three rural communities. The purpose of this study is to increase the level of evidence for community-engaged research methods through a randomized controlled trial. Methods: Two communities will use the SEED Method and one will use a modified Delphi method. We aim to recruit a total of 144 participants (48 per community). The evaluation team will randomize participants to an intervention group or a control group. In addition, we will collect outcome data from the participatory research team members leading the projects in each county (n = 18) and from additional community members who participate in focus groups (n = 32). The primary outcome for all participants will be the change in self-reported civic engagement as measured by the total score on the Individual Mobilization Scale. Discussion: In the context of participatory action to address opioid misuse in rural counties, this study will provide an understanding of the effectiveness of two community engagement methods for increasing civic engagement, as well as the extent to which participants successfully create locally tailored action strategies. The study will also explore how the observed effects differ depending on the participant’s role in the project (stakeholder participant, community research team member, or focus group participant), which is an important consideration for participatory research.
- Adjust your own oxygen mask before helping those around you: an autoethnography of participatory researchSteketee, Abby M.; Archibald, Thomas G.; Harden, Samantha M. (2020-09-03)Background There is a need to unpack the empirical, practical, and personal challenges within participatory approaches advocated to optimize implementation. The unpredictable, chaotic nature of participatory approaches complicates application of implementation theories, methods, and strategies which do not address researchers’ situatedness within participatory processes. As an implementation scientist, addressing one’s own situatedness through critical reflection is important to unearth how conscious and unconscious approaches, including ontological and epistemological underpinnings, influence the participatory context, process, and outcomes. Therefore, the aim of this exploratory work is to investigate the heretofore blind spot toward the lived experience of implementation researchers within the participatory process. Methods We developed an integrated research-practice partnership (IRPP) to inform the implementation of a gestational weight gain (GWG) control program. Within this IRPP, one investigator conducted a 12-month autoethnography. Data collection and triangulation included field notes, cultural artifacts, and systematic timeline tracking. Data analysis included ethnographic-theoretical dialogue and restorying to synthesize key events and epiphanies into a narrative. Results Analysis revealed the unpredicted evolution of the GWG program into a maternal health fair and three themes within the researchers’ lived experience: (1) permeable work boundaries, (2) individual and collective blind spots toward the ontological and epistemological underpinnings of implementation paradigms, and (3) maladaptive behaviors seemingly reinforced by the research culture. These themes contributed to the chaos of implementation and to researchers’ experience of inadequate recovery from cognitive, emotional, and practical demands. These themes also demonstrated the importance of contextual factors, subjectivity, and value-based judgments within implementation research. Conclusion Building on extant qualitative research guidelines, we suggest that researchers anchor their approach to implementation in reflexivity, intentionally and iteratively reflecting on their own situatedness. Through this autoethnography, we have elucidated several strategies based on critical reflection including examining philosophical underpinnings of research, adopting restorative practices that align with one’s values, and embracing personal presence as a foundation of scientific productivity. Within the predominant (post-) positivism paradigms, autoethnography may be criticized as unscientifically subjective or self-indulgent. However, this work demonstrates that autoethnography is a vehicle for third-person observation and first-person critical reflection that is transformative in understanding and optimizing implementation contexts, processes, and outcomes.
- Advancing implementation science in community settings: the implementation strategies applied in communities (ISAC) compilationBalis, Laura E.; Houghtaling, Bailey; Clausen, Whitney; Lane, Hannah; Wende, Marilyn E.; Pereira, Emiliane; McLoughlin, Gabriella M.; Harden, Samantha M. (2024-11-26)Background: Implementation strategies have predominantly been operationalized and studied in clinical settings. Implementation strategies are also needed to improve evidence-based intervention (EBI) integration in community settings, but there is a lack of systematic characterization of their use, which limits generalizability of findings. The goals of this study were to determine which implementation strategies are most used to deliver primary prevention EBIs in community settings, develop a compilation and pragmatic strategy selection process with accompanying guidance tools, and understand practitioners’ preferences for dissemination. Methods: Purposive and snowball sampling was used to recruit community setting researchers and practitioners delivering primary prevention EBIs (nutrition, physical activity, tobacco prevention) in community settings: education, social services, city planning and transportation, workplaces, recreation/sport, faith-based, and other public health organizations. Semi-structured interviews were conducted using a guide based on the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework. Participants were asked to describe barriers experienced and strategies used to overcome them within each RE-AIM dimension. Practitioners were also asked about preferred dissemination strategies, prompted by Diffusion of Innovations theory concepts of sources (who provides information) and channels (how information is provided). A rapid deductive approach was used to analyze findings with a coding matrix aligned with the interview guide. Results: Researchers (n = 10) and practitioners (n = 8) across all targeted settings and intervention outcomes completed interviews. Interviewees shared unique implementation strategies (N = 40) which were used to overcome barriers related to multiple RE-AIM dimensions, most commonly implementation (n = 29) and adoption (n = 27). Most frequently mentioned implementation strategies were conduct pragmatic evaluation (n = 31), provide training (n = 26), change adaptable program components (n = 26), and leverage funding sources (n = 21). Webinars (n = 6) and listservs/newsletters (n = 5) were the most mentioned dissemination channels; national public health organizations (n = 13) were the most mentioned sources. Conclusions: Results reflect commonly used implementation strategies in community settings (e.g., training, technical assistance) and add novel strategies not reflected in current taxonomies. Dissemination preferences suggest the need to involve broad-reaching public health organizations. The resultant compilation (Implementation Strategies Applied in Communities) and strategy selection process provide resources to assist researchers and practitioners in applying strategies and improving EBI delivery in community settings.
- Advancing respirable coal mine dust source apportionment: a preliminary laboratory exploration of optical microscopy as a novel monitoring toolSanta, Nestor; Sarver, Emily A. (2024-04-16)Exposure to respirable coal mine dust (RCMD) can cause chronic and debilitating lung diseases. Real-time monitoring capabilities are sought which can enable a better understanding of dust components and sources. In many underground mines, RCMD includes three primary components which can be loosely associated with three major dust sources: coal dust from the coal seam itself, silicates from the surrounding rock strata, and carbonates from the inert ‘rock dust’ products that are applied to mitigate explosion hazards. A monitor which can reliably partition RCMD between these three components could thus allow source apportionment. And tracking silicates, specifically, could be valuable since the most serious health risks are typically associated with this component-particularly if abundant in crystalline silica. Envisioning a monitoring concept based on field microscopy, and following up on prior research using polarized light, the aim of the current study was to build and test a model to classify respirable-sized particles as either coal, silicates, or carbonates. For model development, composite dust samples were generated in the laboratory by successively depositing dust from high-purity materials onto a sticky transparent substrate, and imaging after each deposition event such that the identity of each particle was known a priori. Model testing followed a similar approach, except that real geologic materials were used as the source for each dust component. Results showed that the model had an overall accuracy of 86.5%, indicating that a field-microscopy based monitor could support RCMD source apportionment and silicates tracking in some coal mines.
- An aeroponic culture system for the study of root herbivory on Arabidopsis thalianaVaughan, Martha M.; Tholl, Dorothea; Tokuhisa, James G. (Biomed Central, 2011-03-10)Background Plant defense against herbivory has been studied primarily in aerial tissues. However, complex defense mechanisms have evolved in all parts of the plant to combat herbivore attack and these mechanisms are likely to differ in the aerial and subterranean environment. Research investigating defense responses belowground has been hindered by experimental difficulties associated with the accessibility and quality of root tissue and the lack of bioassays using model plants with altered defense profiles. Results We have developed an aeroponic culture system based on a calcined clay substrate that allows insect herbivores to feed on plant roots while providing easy recovery of the root tissue. The culture method was validated by a root-herbivore system developed for Arabidopsis thaliana and the herbivore Bradysia spp. (fungus gnat). Arabidopsis root mass obtained from aeroponically grown plants was comparable to that from other culture systems, and the plants were morphologically normal. Bradysia larvae caused considerable root damage resulting in reduced root biomass and water absorption. After feeding on the aeroponically grown root tissue, the larvae pupated and emerged as adults. Root damage of mature plants cultivated in aeroponic substrate was compared to that of Arabidopsis seedlings grown in potting mix. Seedlings were notably more susceptible to Bradysia feeding than mature plants and showed decreased overall growth and survival rates. Conclusions A root-herbivore system consisting of Arabidopsis thaliana and larvae of the opportunistic herbivore Bradysia spp. has been established that mimics herbivory in the rhizosphere. Bradysia infestation of Arabidopsis grown in this culture system significantly affects plant performance. The culture method will allow simple profiling and in vivo functional analysis of root defenses such as chemical defense metabolites that are released in response to belowground insect attack.
- AgroSeek: a system for computational analysis of environmental metagenomic data and associated metadataLiang, Xiao; Akers, Kyle; Keenum, Ishi M.; Wind, Lauren L.; Gupta, Suraj; Chen, Chaoqi; Aldaihani, Reem; Pruden, Amy; Zhang, Liqing; Knowlton, Katharine F.; Xia, Kang; Heath, Lenwood S. (2021-03-10)Background Metagenomics is gaining attention as a powerful tool for identifying how agricultural management practices influence human and animal health, especially in terms of potential to contribute to the spread of antibiotic resistance. However, the ability to compare the distribution and prevalence of antibiotic resistance genes (ARGs) across multiple studies and environments is currently impossible without a complete re-analysis of published datasets. This challenge must be addressed for metagenomics to realize its potential for helping guide effective policy and practice measures relevant to agricultural ecosystems, for example, identifying critical control points for mitigating the spread of antibiotic resistance. Results Here we introduce AgroSeek, a centralized web-based system that provides computational tools for analysis and comparison of metagenomic data sets tailored specifically to researchers and other users in the agricultural sector interested in tracking and mitigating the spread of ARGs. AgroSeek draws from rich, user-provided metagenomic data and metadata to facilitate analysis, comparison, and prediction in a user-friendly fashion. Further, AgroSeek draws from publicly-contributed data sets to provide a point of comparison and context for data analysis. To incorporate metadata into our analysis and comparison procedures, we provide flexible metadata templates, including user-customized metadata attributes to facilitate data sharing, while maintaining the metadata in a comparable fashion for the broader user community and to support large-scale comparative and predictive analysis. Conclusion AgroSeek provides an easy-to-use tool for environmental metagenomic analysis and comparison, based on both gene annotations and associated metadata, with this initial demonstration focusing on control of antibiotic resistance in agricultural ecosystems. Agroseek creates a space for metagenomic data sharing and collaboration to assist policy makers, stakeholders, and the public in decision-making. AgroSeek is publicly-available at https://agroseek.cs.vt.edu/ .
- Allele-specific methylation in the FADS genomic region in DNA from human saliva, CD4+ cells, and total leukocytesRahbar, Elaheh; Waits, Charlotte M. K.; Kirby, Edward H.; Miller, Leslie R.; Ainsworth, Hannah C.; Cui, Tao; Sergeant, Susan; Howard, Timothy D.; Langefeld, Carl D.; Chilton, Floyd H. (2018-04-06)Background Genetic variants within the fatty acid desaturase (FADS) gene cluster (human Chr11) are important regulators of long-chain (LC) polyunsaturated fatty acid (PUFA) biosynthesis in the liver and consequently have been associated with circulating LC-PUFA levels. More recently, epigenetic modifications such as DNA methylation, particularly within the FADS cluster, have been shown to affect LC-PUFA levels. Our lab previously demonstrated strong associations of allele-specific methylation (ASM) between a single nucleotide polymorphism (SNP) rs174537 and CpG sites across the FADS region in human liver tissues. Given that epigenetic signatures are tissue-specific, we aimed to evaluate the methylation status and ASM associations between rs174537 and DNA methylation obtained from human saliva, CD4+ cells and total leukocytes derived from whole blood. The goals were to (1) determine if DNA methylation from these peripheral samples would display similar ASM trends as previously observed in human liver tissues and (2) evaluate the associations between DNA methylation and circulating LC-PUFAs. Results DNA methylation at six CpG sites spanning FADS1 and FADS2 promoter regions and a putative FADS enhancer region were determined in two Caucasian cohorts of healthy volunteers: leukocytes in cohort 1 (n = 89, median age = 43, 35% male) and saliva and CD4+ cells in cohort 2 (n = 32, median age = 41, 41% male). Significant ASM between rs174537 and DNA methylation at three CpG sites located in the FADS2 promoter region (i.e., chr11:61594865, chr11:61594876, chr11:61594907) and one CpG site in the putative enhancer region (chr11:61587979) were observed with leukocytes. In CD4+ cells, significant ASM was observed at CpG sites chr11:61594876 and chr11:61584894. Genotype at rs174537 was significantly associated with DNA methylation from leukocytes. Similar trends were observed with CD4+ cells, but not with saliva. DNA methylation from leukocytes and CD4+ cells also significantly correlated with circulating omega-6 LC-PUFAs. Conclusions We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans.
- Altered microRNA composition in the uterine lumen fluid in cattle (Bos taurus) pregnancies initiated by artificial insemination or transfer of an in vitro produced embryoBiase, Fernando H.; Moorey, Sarah E.; Schnuelle, Julie G.; Rodning, Soren; Ortega, Martha S.; Spencer, Thomas E. (2024-09-13)Background: MicroRNAs (miRNAs) are presented in the uterine lumen of many mammals, and in vitro experiments have determined that several miRNAs are important for the regulation of endometrial and trophoblast functions. Our aim was to identify and contrast the miRNAs present in extracellular vesicles (EVs) in the uterine lumen fluid (ULF) at the onset of attachment in cattle pregnancies (gestation d 18) initiated by artificial insemination (AI) or by the transfer of an in vitro-produced blastocyst (IVP-ET). A third group had no conceptus after the transfer of an IVP embryo. Results: The abundance of 263 annotated miRNAs was quantified in the EVs collected from ULF. There was an increase in the transcript abundance of 20 miRNAs in the ULF EVs from the AI pregnant group, while 4 miRNAs had a lower abundance relative to the group not containing a conceptus. Additionally, 4 miRNAs were more abundant in ULF EVs in the AI pregnant group relative to IVP-ET group (bta-mir-17, bta-mir-7-3, MIR7-1, MIR18A). Specific miRNAs in the ULF EVs were co-expressed with messenger RNAs expressed in extra-embryonic tissues and endometrium, including genes that are known to be their targets. Conclusions: The results provide biological insights into the participation of miRNAs in the regulation of trophoblast proliferation and differentiation, as well as in endometrium receptivity. The knowledge that in vitro cultured embryos can contribute to the altered abundance of specific miRNAs in the uterine lumen can lead to the development of corrective approaches to reduce conceptus losses during the first month of pregnancy in cattle.
- Altered phosphorylation, electrophysiology, and behavior on attenuation of PDE4B action in hippocampusCampbell, Susan L.; van Groen, Thomas; Kadish, Inga; Smoot, Lisa High Mitchell; Bolger, Graeme B. (BMC, 2017)Background: PDE4 cyclic nucleotide phosphodiesterases regulate 3′, 5′ cAMP abundance in the CNS and thereby regulate PKA activity and phosphorylation of CREB, which has been implicated in learning and memory, depression and other functions. The PDE4 isoform PDE4B1 also interacts with the DISC1 protein, implicated in neural development and behavioral disorders. The cellular functions of PDE4B1 have been investigated extensively, but its function(s) in the intact organism remained unexplored. Results: To specifically disrupt PDE4B1, we developed mice that express a PDE4B1-D564A transgene in the hippocampus and forebrain. The transgenic mice showed enhanced phosphorylation of CREB and ERK1/2 in hippocampus. Hippocampal neurogenesis was increased in the transgenic mice. Hippocampal electrophysiological studies showed increased baseline synaptic transmission and enhanced LTP in male transgenic mice. Behaviorally, male transgenic mice showed increased activity in prolonged open field testing, but neither male nor female transgenic mice showed detectable anxiety-like behavior or antidepressant effects in the elevated plus-maze, tail-suspension or forced-swim tests. Neither sex showed any significant differences in associative fear conditioning or showed any demonstrable abnormalities in pre-pulse inhibition. Conclusions: These data support the use of an isoform-selective approach to the study of PDE4B1 function in the CNS and suggest a probable role of PDE4B1 in synaptic plasticity and behavior. They also provide additional rationale and a refined approach to the development of small-molecule PDE4B1-selective inhibitors, which have potential functions in disorders of cognition, memory, mood and affect.
- Altered reward system reactivity for personalized circumscribed interests in autismKohls, Gregor; Antezana, Ligia; Mosner, Maya G.; Schultz, Robert T.; Yerys, Benjamin E. (2018-01-30)Background Neurobiological research in autism spectrum disorders (ASD) has paid little attention on brain mechanisms that cause and maintain restricted and repetitive behaviors and interests (RRBIs). Evidence indicates an imbalance in the brain’s reward system responsiveness to social and non-social stimuli may contribute to both social deficits and RRBIs. Thus, this study’s central aim was to compare brain responsiveness to individual RRBI (i.e., circumscribed interests), with social rewards (i.e., social approval), in youth with ASD relative to typically developing controls (TDCs). Methods We conducted a 3T functional magnetic resonance imaging (fMRI) study to investigate the blood-oxygenation-level-dependent effect of personalized circumscribed interest rewards versus social rewards in 39 youth with ASD relative to 22 TDC. To probe the reward system, we employed short video clips as reinforcement in an instrumental incentive delay task. This optimization increased the task’s ecological validity compared to still pictures that are often used in this line of research. Results Compared to TDCs, youth with ASD had stronger reward system responses for CIs mostly within the non-social realm (e.g., video games) than social rewards (e.g., approval). Additionally, this imbalance within the caudate nucleus’ responsiveness was related to greater social impairment. Conclusions The current data support the idea of reward system dysfunction that may contribute to enhanced motivation for RRBIs in ASD, accompanied by diminished motivation for social engagement. If a dysregulated reward system indeed supports the emergence and maintenance of social and non-social symptoms of ASD, then strategically targeting the reward system in future treatment endeavors may allow for more efficacious treatment practices that help improve outcomes for individuals with ASD and their families.
- The Alternaria genomes database: a comprehensive resource for a fungal genus comprised of saprophytes, plant pathogens, and allergenic speciesDang, Ha X.; Pryor, Barry M.; Peever, Tobin L.; Lawrence, Christopher B. (2015-03-25)Background Alternaria is considered one of the most common saprophytic fungal genera on the planet. It is comprised of many species that exhibit a necrotrophic phytopathogenic lifestyle. Several species are clinically associated with allergic respiratory disorders although rarely found to cause invasive infections in humans. Finally, Alternaria spp. are among the most well known producers of diverse fungal secondary metabolites, especially toxins. Description We have recently sequenced and annotated the genomes of 25 Alternaria spp. including but not limited to many necrotrophic plant pathogens such as A. brassicicola (a pathogen of Brassicaceous crops like cabbage and canola) and A. solani (a major pathogen of Solanaceous plants like potato and tomato), and several saprophytes that cause allergy in human such as A. alternata isolates. These genomes were annotated and compared. Multiple genetic differences were found in the context of plant and human pathogenicity, notably the pro-inflammatory potential of A. alternata. The Alternaria genomes database was built to provide a public platform to access the whole genome sequences, genome annotations, and comparative genomics data of these species. Genome annotation and comparison were performed using a pipeline that integrated multiple computational and comparative genomics tools. Alternaria genome sequences together with their annotation and comparison data were ported to Ensembl database schemas using a self-developed tool (EnsImport). Collectively, data are currently hosted using a customized installation of the Ensembl genome browser platform. Conclusion Recent efforts in fungal genome sequencing have facilitated the studies of the molecular basis of fungal pathogenicity as a whole system. The Alternaria genomes database provides a comprehensive resource of genomics and comparative data of an important saprophytic and plant/human pathogenic fungal genus. The database will be updated regularly with new genomes when they become available. The Alternaria genomes database is freely available for non-profit use at http://alternaria.vbi.vt.edu .