Fralin Life Sciences Institute

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Note: In 2019, the Biocomplexity Institute became part of the Fralin Life Sciences Institute.

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10 Ways to Make an Accessible Collaborative Environment for People with Disabilities
Mortazavigazar, Amir (Virginia Tech Global Change Center, 2022-10-07)
2002 Annual Report
Virginia Bioinformatics Institute (Virginia Bioinformatics Institute, 2002-11-03)
2010 Scientific Report: Virginia Bioinformatics Institute
Virginia Bioinformatics Institute (Virginia Bioinformatics Institute, 2010-06-09)
2022 CeZAP Infectious Diseases Symposium
(Virginia Tech, 2022-10-07)
A program for the symposium held on October 7, 2022, at The Inn at Virginia Tech.
2023 CeZAP Infectious Diseases Research Symposium
(Virginia Tech, 2023-10)
A program for the symposium held on October 6, 2023, at The Inn at Virginia Tech.
3,4-Dihydroxyphenylacetaldehyde synthase and cuticle formation in insects
Liao, Chenghong; Liang, Jing; Han, Qian; Li, Jianyong (2018-06-02)
Cuticle is the most important structure that protects mosquitoes and other insect species from adverse environmental conditions and infections of microorganism. The physiology and biochemistry of insect cuticle formation have been studied for many years and our understanding of cuticle formation and hardening has increased considerably. This is especially true for flexible cuticle. The recent discovery of a novel enzyme that catalyzes the production of 3,4-dihydroxyphenylacetaldehyde (DOPAL) in insects provides intriguing insights concerning the flexible cuticle formation in insects. For convenience, the enzyme that catalyzes the production DOPAL from L-dopa is named DOPAL synthase. In this mini-review, we summarize the biochemical pathways of cuticle formation and hardening in general and discuss DOPAL synthase-mediated protein crosslinking in insect flexible cuticle in particular.
9th Hellbender Symposium
(Virginia Tech. Global Change Center, 2019-06)
The Hellbender Symposium is a biennial event where hellbender researchers from all over the United States and other parts of the world meet to present and discuss their research.
A Tale of Two States: Comparing Implementation of NEPA in Virginia and California
Mortazavigazar, Amir (Virginia Tech Global Change Center, 2023-03-20)
Abscisic Acid: A Novel Nutraceutical for Glycemic Control
Zocchi, Elena; Hontecillas, Raquel; Leber, Andrew; Einerhand, Alexandra; Carbo, Adria; Bruzzone, Santina; Tubau-Juni, Nuria; Philipson, Noah; Zoccoli-Rodriguez, Victoria; Sturla, Laura; Bassaganya-Riera, Josep (Frontiers, 2017-06-13)
Abscisic acid is naturally present in fruits and vegetables, and it plays an important role in managing glucose homeostasis in humans. According to the latest U.S. dietary survey, about 92% of the population might have a deficient intake of ABA due to their deficient intake of fruits and vegetables. This review summarizes the in vitro, preclinical, mechanistic, and human translational findings obtained over the past 15 years in the study of the role of ABA in glycemic control. In 2007, dietary ABA was first reported to ameliorate glucose tolerance and obesity-related inflammation in mice. The most recent findings regarding the topic of ABA and its proposed receptor lanthionine synthetase C-like 2 in glycemic control and their interplay with insulin and glucagon-like peptide-1 suggest a major role for ABA in the physiological response to a glucose load in humans. Moreover, emerging evidence suggests that the ABA response might be dysfunctional in diabetic subjects. Follow on intervention studies in healthy individuals show that low-dose dietary ABA administration exerts a beneficial effect on the glycemia and insulinemia profiles after oral glucose load. These recent findings showing benefits in humans, together with extensive efficacy data in mouse models of diabetes and inflammatory disease, suggest the need for reference ABA values and its possible exploitation of the glycemia-lowering effects of ABA for preventative purposes. Larger clinical studies on healthy, prediabetic, and diabetic subjects are needed to determine whether addressing the widespread dietary ABA deficiency improves glucose control in humans.
Abstracts from the 3rd Conference on Aneuploidy and Cancer: Clinical and Experimental Aspects
Cornish-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 China
Lau, 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.
Accurate human microsatellite genotypes from high-throughput resequencing data using informed error profiles
Highnam, Gareth; Franck, Christopher T.; Martin, Andy; Stephens, Calvin; Puthige, Ashwin; Mittelman, David (Oxford University Press, 2013-01)
Repetitive sequences are biologically and clinically important because they can influence traits and disease, but repeats are challenging to analyse using short-read sequencing technology. We present a tool for genotyping microsatellite repeats called RepeatSeq, which uses Bayesian model selection guided by an empirically derived error model that incorporates sequence and read properties. Next, we apply RepeatSeq to high-coverage genomes from the 1000 Genomes Project to evaluate performance and accuracy. The software uses common formats, such as VCF, for compatibility with existing genome analysis pipelines. Source code and binaries are available at http://github.com/adaptivegenome/repeatseq.
Accurate Strand-Specific Quantification of Viral RNA
Plaskon, Nicole E.; Adelman, Zach N.; Myles, Kevin M. (PLOS, 2009-10-22)
The presence of full-length complements of viral genomic RNA is a hallmark of RNA virus replication within an infected cell. As such, methods for detecting and measuring specific strands of viral RNA in infected cells and tissues are important in the study of RNA viruses. Strand-specific quantitative real-time PCR (ssqPCR) assays are increasingly being used for this purpose, but the accuracy of these assays depends on the assumption that the amount of cDNA measured during the quantitative PCR (qPCR) step accurately reflects amounts of a specific viral RNA strand present in the RT reaction. To specifically test this assumption, we developed multiple ssqPCR assays for the positive-strand RNA virus o'nyong-nyong (ONNV) that were based upon the most prevalent ssqPCR assay design types in the literature. We then compared various parameters of the ONNV-specific assays. We found that an assay employing standard unmodified virus-specific primers failed to discern the difference between cDNAs generated from virus specific primers and those generated through false priming. Further, we were unable to accurately measure levels of ONNV (−) strand RNA with this assay when higher levels of cDNA generated from the (+) strand were present. Taken together, these results suggest that assays of this type do not accurately quantify levels of the anti-genomic strand present during RNA virus infectious cycles. However, an assay permitting the use of a tag-specific primer was able to distinguish cDNAs transcribed from ONNV (−) strand RNA from other cDNAs present, thus allowing accurate quantification of the anti-genomic strand. We also report the sensitivities of two different detection strategies and chemistries, SYBR® Green and DNA hydrolysis probes, used with our tagged ONNV-specific ssqPCR assays. Finally, we describe development, design and validation of ssqPCR assays for chikungunya virus (CHIKV), the recent cause of large outbreaks of disease in the Indian Ocean region.
Activation of PAD4 in NET formation
Rohrbach, Amanda S.; Slade, Daniel J.; Thompson, Paul R.; Mowen, Kerri A. (2012)
Peptidylarginine deiminases, or PADs, convert arginine residues to the non-ribosomally encoded amino acid citrulline in a variety of protein substrates. PAD4 is expressed in granulocytes and is essential for the formation of neutrophil extracellular traps (NETs) via PAD4-mediated histone citrullination. Citrullination of histones is thought to promote NET formation by inducing chromatin decondensation and facilitating the expulsion of chromosomal DNA that is coated with antimicrobial molecules. Numerous stimuli have been reported to lead to PAD4 activation and NET formation. However, how this signaling process proceeds and how PAD4 becomes activated in cells is largely unknown. Herein, we describe the various stimuli and signaling pathways that have been implicated in PAD4 activation and NET formation, including the role of reactive oxygen species generation. To provide a foundation for the above discussion, we first describe PAD4 structure and function, and how these studies led to the development of PAD-specific inhibitors. A comprehensive survey of the receptors and signaling pathways that regulate PAD4 activation will be important for our understanding of innate immunity, and the identification of signaling intermediates in PAD4 activation may also lead to the generation of pharmaceuticals to target NET-related pathogenesis.
ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra
Hinkelmann, 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.
Adaptive Imaging Cytometry to Estimate Parameters of Gene Networks Models in Systems and Synthetic Biology
Ball, David A.; Lux, Matthew W.; Adames, Neil R.; Peccoud, Jean (PLOS, 2014-09-11)
The use of microfluidics in live cell imaging allows the acquisition of dense time-series from individual cells that can be perturbed through computer-controlled changes of growth medium. Systems and synthetic biologists frequently perform gene expression studies that require changes in growth conditions to characterize the stability of switches, the transfer function of a genetic device, or the oscillations of gene networks. It is rarely possible to know a priori at what times the various changes should be made, and the success of the experiment is unknown until all of the image processing is completed well after the completion of the experiment. This results in wasted time and resources, due to the need to repeat the experiment to fine-tune the imaging parameters. To overcome this limitation, we have developed an adaptive imaging platform called GenoSIGHT that processes images as they are recorded, and uses the resulting data to make real-time adjustments to experimental conditions. We have validated this closed-loop control of the experiment using galactose-inducible expression of the yellow fluorescent protein Venus in Saccharomyces cerevisiae. We show that adaptive imaging improves the reproducibility of gene expression data resulting in more accurate estimates of gene network parameters while increasing productivity ten-fold.
Adaptive strategy biases in engineered ecosystems: Implications for plant community dynamics and the provisioning of ecosystem services to people
Krauss, Lauren; Rippy, Megan A. (2022-11-22)
1. Plant communities in green stormwater infrastructure (GSI) such as biofilters play an integral role in ecosystem services provisioning, such that many design manuals now feature plant lists that guide vegetation selection. 2. This study looks at the implications of those lists for biofilter plant communities and their services, focusing on (1) how plants are selected across US climate zones, (2) whether selected plants exhibit adaptive strategy biases (i.e. towards competitive, stress tolerant or ruderal strategies that might impact ecosystem services provisioning) and (3) whether human-induced selection or natural climatic processes underly any biases revealed. 3. Our results suggest that biofilter plant strategies are significantly biased towards stress tolerance or competitiveness (depending on the climate zone) and away from ruderalness relative to the broader pool of native and wetland-adapted native species. 4. Competitive bias was evident in humid-continental climates and stress-tolerant bias in hot coastal/arid climates, with some degree of anti-ruderal bias present across all zones. 5. These biases are correlated with human concerns related to water availability and climate (water conservation; p < 0.05, irrigation; p < 0.1, climate extremes; p < 0.1). They do not appear to reflect strict climatological limits (i.e. limits that are independent of preferences or design constraints imposed by people) because they are not also evident for native plants. 6. The benefits and costs of relaxing these biases are discussed, focusing on the implications for water quality, hydrologic, and cultural services provisioning and the dynamicity of GSI ecosystems, particularly their capacity to self-repair, a prerequisite for the development of self-sustaining GSI.
Addressing the Contribution of Indirect Potable Reuse to Inland Freshwater Salinization
Bhide, Shantanu V.; Grant, Stanley B.; Parker, Emily A.; Rippy, Megan A.; Godrej, Adil N.; Kaushal, Sujay S.; Prelewicz, Gregory; Saji, Niffy; Curtis, Shannon; Vikesland, Peter J.; Maile-Moskowitz, Ayella; Edwards, Marc A.; Lopez, Kathryn; Birkland, Thomas A.; Schenk, Todd (2021-02-02)
Inland freshwater salinity is rising worldwide, a phenomenon called the freshwater salinization syndrome (FSS). We investigate a potential conflict between managing the FSS and indirect potable reuse, the practice of augmenting water supplies through the addition of reclaimed wastewater to surface waters and groundwaters. From time-series data collected over 25 years, we quantify the contributions of three salinity sources—a wastewater reclamation facility and two rapidly urbanizing watersheds—to the rising concentration of sodium (a major ion associated with the FSS) in a regionally important drinking water reservoir in the Mid-Atlantic United States. Sodium mass loading to the reservoir is primarily from watershed runoff during wet weather and reclaimed wastewater during dry weather. Across all timescales evaluated, sodium concentration in the reclaimed wastewater is higher than in outflow from the two watersheds. Sodium in reclaimed wastewater originates from chemicals added during wastewater treatment, industrial and commercial discharges, human excretion, and down-drain disposal of drinking water and sodium-rich household products. Thus, numerous opportunities exist to reduce the contribution of indirect potable reuse to sodium pollution at this site, and the FSS more generally. These efforts will require deliberative engagement with a diverse community of watershed stakeholders and careful consideration of the local political, social, and environmental context.
Advances in Morphodynamic Modeling of Coastal Barriers: A Review
Hoagland, Steven W. H.; Jeffries, Catherine R.; Irish, Jennifer L.; Weiss, Robert; Mandli, Kyle; Vitousek, Sean; Johnson, Catherine M.; Cialone, Mary A. (ASCE, 2023-05-30)
As scientific understanding of barrier morphodynamics has improved, so has the ability to reproduce observed phenomena and predict future barrier states using mathematical models. To use existing models effectively and improve them, it is important to understand the current state of morphodynamic modeling and the progress that has been made in the field. This manuscript offers a review of the literature regarding advancements in morphodynamic modeling of coastal barrier systems and summarizes current modeling abilities and limitations. Broadly, this review covers both event-scale and long-term morphodynamics. Each of these sections begins with an overview of commonly modeled phenomena and processes, followed by a review of modeling developments. After summarizing the advancements toward the stated modeling goals, we identify research gaps and suggestions for future research under the broad categories of improving our abilities to acquire and access data, furthering our scientific understanding of relevant processes, and advancing our modeling frameworks and approaches.
Advancing livestock genomics education and research in developing countries using strategies from the Virginia Tech PREP and IMSD training programs
Smith, Edward J. (2019-07-11)
Our unique and impactful research and education program plan includes distinct activities that target three overlapping phases of each trainee’s tenure, which we define as the “moving in,” “moving through,” and “moving out” phases. During the “moving in” phase, 8 trainees “who need a PREP” will be recruited and assigned to mentors using our proven strategy that is “scholar-driven” and combines mentor qualities such as prior experience, which has resulted in a 98% retention for each of our 3 funding cycles. $409,537 annually or ~2.1 Million for five years. our successful interdisciplinary Initiative for Maximizing Student Development (IMSD) program for pre-doctoral (graduate) and pre-baccalaureate (undergraduate) students from groups underrepresented in careers in the biomedical and behavioral sciences. Our training program is a partnership with departments and interdisciplinary graduate programs which takes advantage of Virginia Tech’s (VT) history of excellence in Engineering and the Behavioral and Life Sciences. With lessons learned in the last eight years, we will continue to recruit across disciplines and from diverse geographic areas and institutions. From the first cycle, 2007-12, a total of 23 pre-doctoral students participated in the VT IMSD program. A total of 16 (or 69.5%) have completed and received the PhD degree; Total Year 1: $467,489.

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