Systems Biology Commons^™

Effect Of Genetic Background On The Dystrophic Phenotype In Mdx Mice., William D Coley, Laurent Bogdanik, Maria Candida Vila, Qing Yu, Terence A Partridge, Kanneboyina Nagaraju, +12 Additional Authors

Genomics and Precision Medicine Faculty Publications

Genetic background significantly affects phenotype in multiple mouse models of human diseases, including muscular dystrophy. This phenotypic variability is partly attributed to genetic modifiers that regulate the disease process. Studies have demonstrated that introduction of the γ-sarcoglycan null allele onto the DBA/2J background confers a more severe muscular dystrophy phenotype than the original strain, demonstrating the presence of genetic modifier loci in the DBA/2J background. To characterize the phenotype of dystrophin deficiency on the DBA/2J background, we created and phenotyped DBA/2J-congenic Dmdmdx mice (D2-mdx) and compared them to the original, C57BL/10ScSn-Dmdmdx (B10-mdx) model. These strains were compared to their respective …

Sidestream Smoke Exposure Increases The Susceptibility Of Airway Epithelia To Adenoviral Infection, Priyanka Sharma, Abimbola O. Kolawole, Susan B. Core, Adriana E. Kajon, Katherine J.D.A. Excoffon

Biological Sciences Faculty Publications

Background: Although significant epidemiological evidence indicates that cigarette smoke exposure increases the incidence and severity of viral infection, the molecular mechanisms behind the increased susceptibility of the respiratory tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses and important causative agents of acute respiratory disease. The Coxsackievirus and adenovirus receptor (CAR) is the primary receptor for many adenoviruses. We hypothesized that cigarette smoke exposure increases epithelial susceptibility to adenovirus infection by increasing the abundance of apical CAR. Methodology and Findings: Cultured human airway epithelial cells (CaLu-3) were used as a model to investigate the effect of sidestream cigarette …

Age-Associated Methylation Suppresses Spry1, Leading To A Failure Of Re-Quiescence And Loss Of The Reserve Stem Cell Pool In Elderly Muscle., Anne Bigot, William J Duddy, Zamalou G Ouandaogo, Elisa Negroni, Virginie Mariot, Svetlana Ghimbovschi, Brennan Harmon, Aurore Wielgosik, Camille Loiseau, Joseph Devaney, Julie Dumonceaux, Gillian Butler-Browne, Vincent Mouly, Stéphanie Duguez

Genomics and Precision Medicine Faculty Publications

The molecular mechanisms by which aging affects stem cell number and function are poorly understood. Murine data have implicated cellular senescence in the loss of muscle stem cells with aging. Here, using human cells and by carrying out experiments within a strictly pre-senescent division count, we demonstrate an impaired capacity for stem cell self-renewal in elderly muscle. We link aging to an increased methylation of the SPRY1 gene, a known regulator of muscle stem cell quiescence. Replenishment of the reserve cell pool was modulated experimentally by demethylation or siRNA knockdown of SPRY1. We propose that suppression of SPRY1 by age-associated …

The Potential For A Blood Test For Scabies, Larry G. Arlian, Hermann Feldmeier, Majorie S. Morgan

Biological Sciences Faculty Publications

Scabies, caused by the mite S. scabiei that burrows in the skin of humans, is a contagious skin disease that affects millions of people worldwide. It is a significant public health burden in economically disadvantaged populations, and outbreaks are common in nursing homes, daycare facilities, schools and workplaces in developed countries. It causes significant morbidity, and in chronic cases, associated bacterial infections can lead to renal and cardiac diseases. Scabies is very difficult to diagnose by the usual skin scrape test, and a presumptive diagnosis is often made based on clinical signs such as rash and itch that can …

Gene Diversification Of An Emerging Pathogen: A Decade Of Mutation In A Novel Fish Viral Hemorrhagic Septicemia (Vhs) Substrain Since Its First Appearance In The Laurentian Great Lakes, Carol A. Stepien, Lindsey R. Pierce, Douglas W. Leaman, Megan D. Niner, Brian S. Shepherd

Biological Sciences Faculty Publications

Viral Hemorrhagic Septicemia virus (VHSv) is an RNA rhabdovirus, which causes one of the world's most serious fish diseases, infecting >80 freshwater and marine species across the Northern Hemisphere. A new, novel, and especially virulent substrain—VHSv-IVb—first appeared in the Laurentian Great Lakes about a decade ago, resulting in massive fish kills. It rapidly spread and has genetically diversified. This study analyzes temporal and spatial mutational patterns of VHSv-IVb across the Great Lakes for the novel non-virion (Nv) gene that is unique to this group of novirhabdoviruses, in relation to its glycoprotein (G), phosphoprotein (P), …

Macroecology Of North American Suckers (Catostomidae): Tests Of Bergmann's And Rapoport's Rules, Stephen J. Jacquemin, Jason C. Doll

Biological Sciences Faculty Publications

Discerning spatial macroecological patterns in freshwater fishes has broad implications for community assembly, ecosystem dynamics, management, and conservation. This study explores the potential interspecific covariation of geographic range (Rapoport's rule) and body size (Bergmann's rule) with latitude in North American sucker fishes (Cypriniformes: Catostomidae). While numerous tests of Rapoport's and Bergmann's rules are documented in the literature, comparatively few of these studies have specifically tested for these patterns, and none have incorporated information reflecting shared ancestry into analyses of North American freshwater fish through a hierarchical model. This study utilized a hierarchical modeling approach with Bayesian inference to evaluate the …

Bioregulatory Systems Medicine: An Innovative Approach To Integrating The Science Of Molecular Networks, Inflammation, And Systems Biology With The Patient's Autoregulatory Capacity?, Alyssa W Goldman, Yvonne Burmeister, Konstantin Cesnulevicius, Martha Herbert, Mary Kane, David Lescheid, Timothy Mccaffrey, Myron Schultz, Bernd Seilheimer, Alta Smit, Georges St Laurent, Brian Berman

Medicine Faculty Publications

Bioregulatory systems medicine (BrSM) is a paradigm that aims to advance current medical practices. The basic scientific and clinical tenets of this approach embrace an interconnected picture of human health, supported largely by recent advances in systems biology and genomics, and focus on the implications of multi-scale interconnectivity for improving therapeutic approaches to disease. This article introduces the formal incorporation of these scientific and clinical elements into a cohesive theoretical model of the BrSM approach. The authors review this integrated body of knowledge and discuss how the emergent conceptual model offers the medical field a new avenue for extending the …

Century-Long Warming Trends In The Upper Water Column Of Lake Tanganyika, Benjamin Kraemer, Simon Hook, Timo Huttula, Pekka Kotilainen, Catherine M. O'Reilly, Anu Peltonen, Pierre-Denis Plisnier, Jouko Sarvala, Rashid Tamatamah, Yvonne Vadeboncoeur, Bernhard Wehrli, Peter B. Mcintyre

Biological Sciences Faculty Publications

Lake Tanganyika, the deepest and most voluminous lake in Africa, has warmed over the last century in response to climate change. Separate analyses of surface warming rates estimated from in situ instruments, satellites, and a paleolimnological temperature proxy (TEX86) disagree, leaving uncertainty about the thermal sensitivity of Lake Tanganyika to climate change. Here, we use a comprehensive database of in situ temperature data from the top 100 meters of the water column that span the lake’s seasonal range and lateral extent to demonstrate that long-term temperature trends in Lake Tanganyika depend strongly on depth, season, and latitude. The observed spatiotemporal …

Morphometry And Average Temperature Affect Lake Stratification Responses To Climate Change, Benjamin Kraemer, Orlane Anneville, Sudeep Chandra, Margaret Dix, Esko Kuusisto, David M. Livingstone, Alon Rimmer, S. Geoffrey Schladow, Eugene Silow, Lewis M. Sitoki, Rashid Tamatamah, Yvonne Vadeboncoeur, Peter B. Mcintyre

Biological Sciences Faculty Publications

Climate change is affecting lake stratification with consequences for water quality and the benefits that lakes provide to society. Here we use long-term temperature data (1970–2010) from 26 lakes around the world to show that climate change has altered lake stratification globally and that the magnitudes of lake stratification changes are primarily controlled by lake morphometry (mean depth, surface area, and volume) and mean lake temperature. Deep lakes and lakes with high average temperatures have experienced the largest changes in lake stratification even though their surface temperatures tend to be warming more slowly. These results confirm that the nonlinear relationship …

Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr.

Honors Scholar Theses

Repeated concussive traumatic brain injury (rcTBI) is the most prominent form of head injury affecting the brain, with an estimated 1.7 million Americans affected each year (Kuhn 2012). Neurologists have been concerned about the danger of repeated head impacts since the 1920’s, but researchers have only begun to understand the long-term effects of rcTBI (McKee 2009). Although symptoms can be as mild as dizziness, current research suggests that multiple concussions can lead to a progressive degenerative brain disease known as chronic traumatic encephalopathy (CTE) (Luo 2008, McKee 2009, Kane 2013). Research on the brain is just beginning to scratch the …

The Heritability Of Shell Morphometrics In The Freshwater Pulmonate Gastropod Physa, Robert T. Dillon Jr., Stephen J. Jacquemin

Biological Sciences Faculty Publications

The cosmopolitan freshwater pulmonate snail Physa acuta hybridizes readily with Physa carolinae in the laboratory, although their F1 progeny are sterile. The two species differ qualitatively in shell shape, the former bearing a more globose shell and the latter more fusiform. We performed a hybridization experiment, measuring a set of 14 traditional (linear) and landmark-based shell morphological variables on even-aged parents and their offspring from both hybrids and purebred control lines. Parent-offspring regression yielded a strikingly high heritability estimate for score on the first relative warp axis, h² = 0.819 ± 0.073, a result that would seem to confirm …

Targeted Single Molecule Sequencing Methodology For Ovarian Hyperstimulation Syndrome., Funda Orkunoglu-Suer, Arthur F. Harralson, David Frankfurter, Paul Gindoff, Travis J. O'Brien

Genomics and Precision Medicine Faculty Publications

BACKGROUND: One of the most significant issues surrounding next generation sequencing is the cost and the difficulty assembling short read lengths. Targeted capture enrichment of longer fragments using single molecule sequencing (SMS) is expected to improve both sequence assembly and base-call accuracy but, at present, there are very few examples of successful application of these technologic advances in translational research and clinical testing. We developed a targeted single molecule sequencing (T-SMS) panel for genes implicated in ovarian response to controlled ovarian hyperstimulation (COH) for infertility.

RESULTS: Target enrichment was carried out using droplet-base multiplex polymerase chain reaction (PCR) technology (RainDance®) …

Adenovirus Entry From The Apical Surface Of Polarized Epithelia Is Facilitated By The Host Innate Immune Response, Poornima L.N. Kotha, Priyanka Sharma, Abimbola O. Kolawole, Ran Yan, Mahmoud Alghamri, Trisha L. Brockman, Julian Gomez-Cambronero, Julian Cambronero

Biological Sciences Faculty Publications

Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAR^Ex8 may be to facilitate host innate immunity. We show that IL-8, …

The Mayfly Newsletter, Peter M. Grant

The Mayfly Newsletter

The Mayfly Newsletter is the official newsletter of the Permanent Committee of the International Conferences on Ephemeroptera.

The Quest For Ash Resistance To Eab: Towards A Mechanistic Understanding, Daniel A. Herms, Don Cipollini, K. S. Knight, J. L. Koch, T. M. Poland, Chad Michael Rigsby, Justin G.A. Whitehill, Pierluigi Bonello

Biological Sciences Faculty Publications

Since emerald ash borer (EAB), Agrilus planipennis, was discovered in North America in 2002, it has killed many millions of ash trees in North America, and ash mortality now exceeds 99% near the epicenter of the invasion in southeast Michigan (Klooster et al. 2014). The development of EAB-resistant ash trees will be critical for restoration of ash in natural and urban forests. Goals of our collaboration are to identify, breed and screen ash germplasm for EAB resistance and silvicultural traits; and identify mechanisms of EAB resistance to facilitate breeding and screening.

Genetic Modifiers Of Duchenne Muscular Dystrophy And Dilated Cardiomyopathy., Andrea Barp, Luca Bello, Luisa Politano, Paola Melacini, Chiara Calore, Eric P. Hoffman, +16 Additional Authors

Genomics and Precision Medicine Faculty Publications

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m2 as …

Transcriptional Pathways Associated With Skeletal Muscle Changes After Spinal Cord Injury And Treadmill Locomotor Training., Celine Baligand, Yi-Wen Chen, Fan Ye, Sachchida Nand Pandey, San-Huei Lai, Min Liu, Krista Vandenborne

Genomics and Precision Medicine Faculty Publications

The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and …

The Implications Of Hiv Treatment On The Hiv-Malaria Coinfection Dynamics: A Modeling Perspective, F. Nyabadza, B. T. Bekele, Megan A. Rúa, D. M. Malonza, N. Chiduku, M. Kgosimore

Biological Sciences Faculty Publications

Most hosts harbor multiple pathogens at the same time in disease epidemiology. Multiple pathogens have the potential for interaction resulting in negative impacts on host fitness or alterations in pathogen transmission dynamics. In this paper we develop a mathematical model describing the dynamics of HIV-malaria coinfection. Additionally, we extended our model to examine the role treatment (of malaria and HIV) plays in altering populations’ dynamics. Our model consists of 13 interlinked equations which allow us to explore multiple aspects of HIV-malaria transmission and treatment. We perform qualitative analysis of the model that includes positivity and boundedness of solutions. Furthermore, we …

Ectomycorrhizal Fungal Communities And Enzymatic Activities Vary Across An Ecotone Between A Forest And Field, Megan A. Rúa, Becky Moore, Nicole Hergott, Lily Van, Colin R. Jackson, Jason D. Hoeksema

Biological Sciences Faculty Publications

Extracellular enzymes degrade macromolecules into soluble substrates and are important for nutrient cycling in soils, where microorganisms, such as ectomycorrhizal (ECM) fungi, produce these enzymes to obtain nutrients. Ecotones between forests and fields represent intriguing arenas for examining the effect of the environment on ECM community structure and enzyme activity because tree maturity, ECM composition, and environmental variables may all be changing simultaneously. We studied the composition and enzymatic activity of ECM associated with loblolly pine (Pinus taeda) across an ecotone between a forest where P. taeda is established and an old field where P. taeda saplings had been growing …

Population Differentiation And Habitat Selection Of A Montane Red Fox Population In The Greater Yellowstone Ecosystem, Patrick Cross

Graduate Student Theses, Dissertations, & Professional Papers

Montane red fox (Vulpes vulpes) populations across the western United States are genetically and morphologically distinct from foxes at lower elevations. These montane populations also share a preference for subalpine forest habitats. One hypothesis is that they stem from boreal forest-associated ancestors that expanded during the Pleistocene when boreal forests extended farther south than they do today. Forest habitat selection may therefore aid the persistence of native populations surrounded by non-native conspecifics. Alternatively, this behavior may be an avoidance mechanism in response to competition with larger coyotes (Canis latrans), or a product of the fox's natural adaptability. The red fox …

Habitat Eradication And Cropland Intensification May Reduce Parasitoid Diversity And Natural Pest Control Services In Annual Crop Fields, D. K. Letourneau, Sara G. Bothwell Allen, Robert R. Kula, Michael J. Sharkey, John O. Stireman Iii

Biological Sciences Faculty Publications

California’s central coast differs from many agricultural areas in the U.S., which feature large tracts of monoculture production fields and relatively simple landscapes. Known as the nation’s salad bowl, and producing up to 90% of U.S. production of lettuces, broccoli and Brussels sprouts, this region is a mosaic of fresh vegetable fields, coastal meadow, chaparral shrubs, riparian and woodland habitat. We tested for relationships between the percent cover of crops, riparian and other natural landscape vegetation and the species richness of parasitic wasps and flies foraging in crops, such as broccoli, kale and cauliflower, and interpreted our results with respect …

Continuing Progress Towards A Phylogeny Of Tachinidae, John O. Stireman Iii, James E. O'Hara, John K. Moulton, Pierfilippo Cerretti, Isaac S. Winkler, Jeremy D. Blaschke, Z. L. Burington

Biological Sciences Faculty Publications

Readers of this newsletter are likely familiar with our ongoing project to establish a framework phylogeny of world Tachinidae (see articles in The Tachinid Times 26 and 27). This collaborative project, involving myself, Jim O’Hara, Kevin Moulton, Pierfilippo Cerretti, Isaac Winkler and a long list of collaborating tachinidophiles was initiated in 2012 with funding from the U.S. National Science Foundation. Our goal is to produce a robust phylogenetic framework of Tachinidae that can be used to inform tachinid taxonomy, systematics research, and the patterns of tachinid evolution. In previous issues of The Tachinid Times we summarized our progress to date …

A New Species And Synonymy Of The Neotropical Eucelatoria Townsend And Redescription Of Myiodoriops Townsend, Diego J. Inclán, John O. Stireman Iii

Biological Sciences Faculty Publications

The New World tropics represents the most diverse region for tachinid parasitoids (Diptera: Tachinidae), but it also contains the most narrowly defined, and possibly the most confusing, tachinid genera of any biogeographic region. This over-splitting of genera and taxonomic confusion has limited progress toward our understanding the family in this region and much work is needed to revise, redefine, and make sense of the profusion of finely split taxa. In a recent analysis of the Neotropical genus Erythromelana Townsend, two species previously assigned to this genus, Euptilodegeeria obumbrata (Wulp) and Myiodoriops marginalis Townsend were reinstated as monotypic genera. In the …

Development And Evaluation Of A Model For Secondary Evolution Educators’ Professional Development Needs, William L. Romine, Ellen Barnett, Patricia J. Friedrichsen, Aaron J. Sickel

Biological Sciences Faculty Publications

Background

Professional development (PD) efforts have improved acceptance and pedagogical practice related to the theory of evolution in high school biology teachers. However, these teachers express need for more PD related to evolution. It therefore becomes necessary to understand teachers’ PD needs prior to structuring PD efforts.

Methods

We formulated and validated a model to explain secondary teachers’ PD needs using data from a survey of 276 secondary biology teachers who reported teaching evolution.

Results

In addition to reliable subscales, we found that obstacles to teaching evolution, school and community support for evolution instruction, confidence in evolution instruction, and prior …

White Fringetree, Chionanthus Virginicus, As A Novel Larval Host For Emerald Ash Boer, Don Cipollini

Biological Sciences Faculty Publications

Emerald ash borer is an invasive Asian pest of ash species in North America. All North American species of ash tested so far are susceptible to it, but there are no published reports of this insect developing fully in non-ash hosts in the field in North America. I report here evidence that EAB can attack and complete development in white fringetree, Chionanthus virginicus L., a species native to the southeastern U.S. that is also planted ornamentally.

Mechanisms Of Ash Resistance To Emerald Ash Borer: Progress And Gaps, Caterina Villari, Justin G.A. Whitehill, Don Cipollini, Daniel A. Herms, Pierluigi Bonello

Biological Sciences Faculty Publications

The emerald ash borer (EAB) invasion of North America has caused widespread mortality of native ash, and is threatening the native ash resources. As a consequence of its devastating impact, EAB has caught the attention of the scientific community, and several studies have focused on different aspects of the biology and behavior of this pest, including its interaction with host defenses. Here we present a review of the published literature on mechanisms of ash resistance to EAB, the understanding of which, despite starting from a tabula rasa, has achieved significant progress in the last few years.

Spatial Variation In Carbon And Nitrogen In Cultivated Soils In Henan Province, China: Potential Effect On Crop Yield, Xuelin Zhang, Qun Wang, Frank S. Gilliam, Yilun Wang, Feina Cha, Chaohai Li

Biological Sciences Faculty Research

Improved management of soil carbon (C) and nitrogen (N) storage in agro-ecosystems represents an important strategy for ensuring food security and sustainable agricultural development in China. Accurate estimates of the distribution of soil C and N stores and their relationship to crop yield are crucial to developing appropriate cropland management policies. The current study examined the spatial variation of soil organic C (SOC), total soil N (TSN), and associated variables in the surface layer (0–40 cm) of soils from intensive agricultural systems in 19 counties within Henan Province, China, and compared these patterns with crop yield. Mean soil C and …

Predation Risk, Elk, And Aspen: Comment, Robert L. Beschta, Cristina Eisenberg, John W. Laundre, William J. Ripple, Thomas P. Rooney

Biological Sciences Faculty Publications

No abstract provided.

The Mayfly Newsletter, Peter M. Grant

The Mayfly Newsletter

The Mayfly Newsletter is the official newsletter of the Permanent Committee of the International Conferences on Ephemeroptera.

A Quantitative Analysis Of Kalandars And Captive Bears In Pakistan, Thomas P. Rooney, Kendra C. Millam

Biological Sciences Faculty Publications

In 2013, the Bioresource Research Centre (Islamabad, Pakistan) conducted a comprehensive census of the remaining dancing and bear-baiting bears in Pakistan. This involved locating and counting the actual involved bears and bear keepers (kalandars), collecting detailed socio-economic data from the bear-keepers, and identifying attitudes and key drivers behind this livelihood. This report summarizes the findings from the census, reveals relationships in the data that are not immediately apparent, and identifies potential leverage points for ongoing campaign efforts.