Systems Biology Commons^™

Upregulated Il-1Β In Dysferlin-Deficient Muscle Attenuates Regeneration By Blunting The Response To Pro-Inflammatory Macrophages., Tatiana V. Cohen, Gina M. Many, Bryan D. Fleming, Viola F. Gnocchi, Svetlana Ghimbovschi, David M. Mosser, Eric P. Hoffman, Terence A. Partridge

Genomics and Precision Medicine Faculty Publications

BACKGROUND: Loss-of-function mutations in the dysferlin gene (DYSF) result in a family of muscle disorders known collectively as the dysferlinopathies. Dysferlin-deficient muscle is characterized by inflammatory foci and macrophage infiltration with subsequent decline in muscle function. Whereas macrophages function to remove necrotic tissue in acute injury, their prevalence in chronic myopathy is thought to inhibit resolution of muscle regeneration. Two major classes of macrophages, classical (M1) and alternative (M2a), play distinct roles during the acute injury process. However, their individual roles in chronic myopathy remain unclear and were explored in this study.

METHODS: To test the roles of the two …

From Genome To Structure And Back Again: A Family Portrait Of The Transcarbamylases., Dashuang Shi, Norma M. Allewell, Mendel Tuchman

Genomics and Precision Medicine Faculty Publications

No abstract provided.

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 …

Elusive Sources Of Variability Of Dystrophin Rescue By Exon Skipping., Maria Candida Vila, Margaret Benny Klimek, James S Novak, Sree Rayavarapu, Kitipong Uaesoontrachoon, Jessica F Boehler, Heather Gordish-Dressman, Terence A Partridge, Kristy J. Brown, Yetrib Hathout, John Van Den Anker, Eric P. Hoffman, Kanneboyina Nagaraju, +7 Additional Authors

Genomics and Precision Medicine Faculty Publications

BACKGROUND: Systemic delivery of anti-sense oligonucleotides to Duchenne muscular dystrophy (DMD) patients to induce de novo dystrophin protein expression in muscle (exon skipping) is a promising therapy. Treatment with Phosphorodiamidate morpholino oligomers (PMO) lead to shorter de novo dystrophin protein in both animal models and DMD boys who otherwise lack dystrophin; however, restoration of dystrophin has been observed to be highly variable. Understanding the factors causing highly variable induction of dystrophin expression in pre-clinical models would likely lead to more effective means of exon skipping in both pre-clinical studies and human clinical trials.

METHODS: In the present study, we investigated …

Annexin A1 Deficiency Does Not Affect Myofiber Repair But Delays Regeneration Of Injured Muscles., Evgenia Leikina, Aurelia Defour, Kamran Melikov, Jack H Van Der Meulen, Kanneboyina Nagaraju, Shivaprasad Bhuvanendran, Claudia Gebert, Karl Pfeifer, Leonid V. Chernomordik, Jyoti K. Jaiswal

Genomics and Precision Medicine Faculty Publications

Repair and regeneration of the injured skeletal myofiber involves fusion of intracellular vesicles with sarcolemma and fusion of the muscle progenitor cells respectively. In vitro experiments have identified involvement of Annexin A1 (Anx A1) in both these fusion processes. To determine if Anx A1 contributes to these processes during muscle repair in vivo, we have assessed muscle growth and repair in Anx A1-deficient mouse (AnxA1-/-). We found that the lack of Anx A1 does not affect the muscle size and repair of myofibers following focal sarcolemmal injury and lengthening contraction injury. However, the lack of Anx A1 delayed muscle regeneration …

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 …

In-Silico Models For Capturing The Static And Dynamic Characteristics Of Robustness Within Complex Networks, Bhanu K. Kamapantula

Theses and Dissertations

Understanding the role of structural patterns within complex networks is essential to establish the governing principles of such networks. Social networks, biological networks, technological networks etc. can be considered as complex networks where information processing and transport plays a central role. Complexity in these net works can be due to abstraction, scale, functionality and structure. Depending on the abstraction each of these can be categorized further. Gene regulatory networks are one such category of biological networks. Gene regulatory networks (GRNs) are assumed to be robust under internal and external perturbations. Network motifs such as feed-forward loop motif and bifan motif …

Acclimation, Adaptation, Traits And Trade-Offs In Plankton Functional Type Models: Reconciling Terminology For Biology And Modelling, Kevin J. Flynn, Michael St. John, John A. Raven, David O. F. Skibinski, J. Icarus Allen, Aditee Mitra, Eileen E. Hofmann

CCPO Publications

We propose definitions in terminology to enhance ongoing collaborations between biologists and modellers on plankton ecology. Organism "functional type" should refer to commonality in ecology not biogeochemistry; the latter is largely an emergent property of the former, while alignment with ecology is also consistent with usage in terrestrial science. Adaptation should be confined, as in genetics, to consideration of species inter-generational change; most so-called "adaptive" plankton models are thus acclimative, modifying vital rates in response to stimuli. Trait trade-off approaches should ideally only be considered for describing intra-generational interactions; in applications between generations, and certainly between unrelated species, such concepts …

Graph-Based Regularization In Machine Learning: Discovering Driver Modules In Biological Networks, Xi Gao

Theses and Dissertations

Curiosity of human nature drives us to explore the origins of what makes each of us different. From ancient legends and mythology, Mendel's law, Punnett square to modern genetic research, we carry on this old but eternal question. Thanks to technological revolution, today's scientists try to answer this question using easily measurable gene expression and other profiling data. However, the exploration can easily get lost in the data of growing volume, dimension, noise and complexity. This dissertation is aimed at developing new machine learning methods that take data from different classes as input, augment them with knowledge of feature relationships, …

The Sensitivity Of Soil Respiration To Soil Temperature, Moisture, And Carbon Supply At The Global Scale, Andrew Hursh

Graduate Student Theses, Dissertations, & Professional Papers

Soil respiration is one of the most important terms in the global carbon budget, yet we know very little about how important environmental factors control this process at the global scale. Soils contain more carbon than terrestrial biomass and the atmosphere combined and contribute ten times more carbon dioxide to the atmosphere each year than the burning of fossil fuels. This study provides new insight on the factors driving soil respiration at the global scale by assimilating satellite observations of soil moisture, temperature, and net primary productivity with the Global Soil Respiration Database (SRDB).While temperature, moisture, carbon supply and other …

High Rates Of Hiv Seroconversion In Pregnant Women And Low Reported Levels Of Hiv Testing Among Male Partners In Southern Mozambique: Results From A Mixed Methods Study, Caroline De Schacht, Heather J. Hoffman, Nedio Mabunda, Carlota Lucas, Catharina L. Alons, Ana Madonela, Adolfo Vubil, Orlando C. Ferreira, Nurbai Calu, Iolanda S. Santos, Ilesh V. Jani, Laura Guay

Genomics and Precision Medicine Faculty Publications

Introduction

Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV. Identification and support for HIV negative pregnant women and their partners, particularly serodiscordant couples, are critical. A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy, associated risk factors and factors influencing partner's HIV testing.

Methods

Between April 2008 and November 2011, a prospective cohort of 1230 HIV negative pregnant women was followed during pregnancy. A structured questionnaire, HIV testing, and collection of dried blood spots were done at 2–3 scheduled visits. HIV incidence rates were calculated by repeat HIV testing …

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 …

Whole Exome Sequencing In Family Trios Reveals De Novo Mutations In Pura As A Cause Of Severe Neurodevelopmental Delay And Learning Disability, David Hunt, Richard J. Leventer, Cas Simons, Ryan J. Taft, Kathryn J. Swoboda, Mary Gawne-Cain, Alex C. Magee, Perter D. Turnpenny, Diana Baralle

Genomics and Precision Medicine Faculty Publications

Background De novo mutations are emerging as an important cause of neurocognitive impairment, and whole exome sequencing of case-parent trios is a powerful way of detecting them. Here, we report the findings in four such trios.

Methods The Deciphering Developmental Disorders study is using whole exome sequencing in family trios to investigate children with severe, sporadic, undiagnosed developmental delay. Three of our patients were ascertained from the first 1133 children to have been investigated through this large-scale study. Case 4 was a phenotypically isolated case recruited into an undiagnosed rare disorders sequencing study.

Results Protein-altering de novo mutations in PURA …

Identification Of Cell Signaling Pathway Regulated By Micrornas In Cancer Cells Using A Systems Biological Approach, Sangbae Kim

Dissertations and Theses (Open Access)

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression via imperfect binding of the miRNA to specific sites in the 3' untranslated region of the mRNAs. Because prediction of miRNA targets is an essential step for understanding the functional roles of miRNAs, many computational approaches have been developed to identify miRNA targets. However, identifying targets remains challenging due to the inherent limitation of current prediction approaches based on imperfect complementarity between miRNA and its target mRNAs. To overcome these current limitations, we developed a novel correlation-based approach that is sequence independence to predict functional targets of miRNAs by …

Quantitative Analysis And Imaging-Based Insights Into The Characteristics And Mechanisms Of Yeast Pattern Formation, Lin Chen

Dissertations and Theses (Open Access)

Biofilm formation is a common lifestyle adapted by bacteria and fungi in response to various environmental stresses. Bacterial and fungal biofilms adhering to medical devices convey resistance to antibiotics or biocides, causing high rates of clinical infections. Microorganisms are protected from harsh environmental conditions by reduced stress penetration through the complex biofilm architecture with distinct patterns. Although the molecular regulations of surface patterning have been well characterized in bacteria, the mechanisms underlying the complex pattern formation in eukaryotic biofilms remain unclear.

This dissertation aims to investigate the salient features of robust colony expansion in yeast biofilms and the processes driving …

The Cedar Point Experience, 40 Years Of Field Based, Experiential Learning, Jon Garbisch

Discipline-Based Education Research Group Speaker Series

The Cedar Point Experience was born in the summer of 1975. At the urging of several biology faculty UNL leased the Goodall Cedar Point Girlscout Camp and offered a broad range of field based courses exploiting the local environment as their classroom. These instructors also had a strong interest in the area as a base for their own research. Today the UNL Cedar Point Biological Station with a few additional buildings can support around 100 people with full service dining, housing, classroom and lab space.

The instructional model has remained unchanged for the past 40 years. Field based or place …

Affinity Proteomics Within Rare Diseases: A Bio‐Nmd Study For Blood Biomarkers Of Muscular Dystrophies, Brucu Ayoglu, Amina Chaouch, Hans Lochmuller, Luisa Politano, Enrico Bertini, Sebahattin Cirak, +17 Additional Authors

Genomics and Precision Medicine Faculty Publications

Despite the recent progress in the broad‐scaled analysis of proteins in body fluids, there is still a lack in protein profiling approaches for biomarkers of rare diseases. Scarcity of samples is the main obstacle hindering attempts to apply discovery driven protein profiling in rare diseases. We addressed this challenge by combining samples collected within the BIO‐NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy using an antibody bead array platform with 384 antibodies. Based on concordance in statistical significance and confirmatory results obtained from analysis of both serum and plasma, we identified eleven …

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.

Asynchronous Remodeling Is A Driver Of Failed Regeneration In Duchenne Muscular Dystrophy, Sherry Dadgar, Zuyi Wang, Helen Johnston, Akanchha Kesari, Kanneboyina Nagaraju, Yi-Wen Chen, D. Ashley Hill, Terence A. Partridge, Robert J. Freishtat, Javad Nazarian, Jianhua Xuan, Yue Wang, Eric P. Hoffman

Genomics and Precision Medicine Faculty Publications

We sought to determine the mechanisms underlying failure of muscle regeneration that is observed in dystrophic muscle through hypothesis generation using muscle profiling data (human dystrophy and murine regeneration). We found that transforming growth factor β-centered networks strongly associated with pathological fibrosis and failed regeneration were also induced during normal regeneration but at distinct time points. We hypothesized that asynchronously regenerating microenvironments are an underlying driver of fibrosis and failed regeneration. We validated this hypothesis using an experimental model of focal asynchronous bouts of muscle regeneration in wild-type (WT) mice. A chronic inflammatory state and reduced mitochondrial oxidative capacity are …

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.

Rapid Identification Of A Novel Complex I Mt-Nd2 M.10134c>A Mutation In A Leigh Syndrome Patient, David K. Miller, Minal J. Menezes, Cas Simons, Lisa G. Riley, Sandra T. Cooper, Sean M. Grimmond, David R. Thorburn, John Christodoulou, Ryan J. Taft

Genomics and Precision Medicine Faculty Publications

Leigh syndrome (LS) is a rare progressive multi-system neurodegenerative disorder, the genetics of which is frequently difficult to resolve. Rapid determination of the genetic etiology of LS in a 5-year-old girl facilitated inclusion in Edison Pharmaceutical’s phase 2B clinical trial of EPI-743. SNP-arrays and high-coverage whole exome sequencing were performed on the proband, both parents and three unaffected siblings. Subsequent multi-tissue targeted high-depth mitochondrial sequencing was performed using custom long-range PCR amplicons. Tissue-specific mutant load was also assessed by qPCR. Complex I was interrogated by spectrophotometric enzyme assays and Western Blot. No putatively causal mutations were identified in nuclear-encoded genes. …