Systems Biology Commons^™

An Analysis Of Dna Methylation In Human Adipose Tissue Reveals Differential Modification Of Obesity Genes Before And After Gastric Bypass And Weight Loss, Miles C. Benton, Alice Johnstone, David Eccles, Brennan Harmon, Mark T. Hayes, Rod A. Lea, Lyn Griffiths, Eric P. Hoffman, Richard S. Stubbs, Donia Macartney-Coxson

Genomics and Precision Medicine Faculty Publications

Background

Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans.

Results

Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is …

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.

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 …

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 …

'In' Or 'As' Space?: A Model Of Complexity, With Philosophical, Simulatory, And Empirical Ramifications, Charles H. Smith

DLPS Faculty Publications

A General Systems model based on ideas originating with the writings of Benedict de Spinoza is described, starting with its philosophical underpinnings, and proceeding on to its relation to modern systems concepts, including attempts to simulate the relationships posed, and measure real world structures. Central to the idea is the notion that spatial extension may not have a prior existence, but emerges only through an entropy maximization process in which information and energy exchange is balanced among some limited number of subsystems that in sum comprise any given functioning complex system. Related published empiricism concerning geographical/geological systems – the hypsometry …

The N-Acetylglutamate Synthase Family: Structures, Function And Mechanisms, Dashuang Shi, Norma M. Allewell, Mendel Tuchman

Genomics and Precision Medicine Faculty Publications

N-acetylglutamate synthase (NAGS) catalyzes the production of N-acetylglutamate (NAG) from acetyl-CoA and L-glutamate. In microorganisms and plants, the enzyme functions in the arginine biosynthetic pathway, while in mammals, its major role is to produce the essential co-factor of carbamoyl phosphate synthetase 1 (CPS1) in the urea cycle. Recent work has shown that several different genes encode enzymes that can catalyze NAG formation. A bifunctional enzyme was identified in certain bacteria, which catalyzes both NAGS and N-acetylglutamate kinase (NAGK) activities, the first two steps of the arginine biosynthetic pathway. Interestingly, these bifunctional enzymes have higher sequence similarity to vertebrate NAGS than …

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 …

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 …

Culture Conditions Affect Expression Of Dux4 In Fshd Myoblasts, Sachchida Nand Pandey, Hunain Khawaja, Yi-Wen Chen

Genomics and Precision Medicine Faculty Publications

Facioscapulohumeral muscular dystrophy (FSHD) is believed to be caused by aberrant expression of double homeobox 4 (DUX4) due to epigenetic changes of the D4Z4 region at chromosome 4q35. Detecting DUX4 is challenging due to its stochastic expression pattern and low transcription level. In this study, we examined different cDNA synthesis strategies and the sensitivity for DUX4 detection. In addition, we investigated the effects of dexamethasone and knockout serum replacement (KOSR) on DUX4 expression in culture. Our data showed that DUX4 was consistently detected in cDNA samples synthesized using Superscript III. The sensitivity of DUX4 detection was higher in the samples …

Muscular Dystrophy In The Mdx Mouse Is A Severe Myopathy Compounded By Hypotrophy, Hypertrophy And Hyperplasia., William Duddy, Stephanie Duguez, Helen Johnston, Tatiana V. Cohen, Aditi Phadke, Heather Gordish-Dressman, Kanneboyina Nagaraju, Viola Gnocchi, Siewhui Low, Terence Partridge

Genomics and Precision Medicine Faculty Publications

Background

Preclinical testing of potential therapies for Duchenne muscular dystrophy (DMD) is conducted predominantly of the mdx mouse. But lack of a detailed quantitative description of the pathology of this animal limits our ability to evaluate the effectiveness of putative therapies or their relevance to DMD.

Methods

Accordingly, we have measured the main cellular components of muscle growth and regeneration over the period of postnatal growth and early pathology in mdx and wild-type (WT) mice; phalloidin binding is used as a measure of fibre size, myonuclear counts and BrdU labelling as records of myogenic activity.

Results

We confirm a two-phase …

The Actn3 R577x Polymorphism Is Associated With Cardiometabolic Fitness In Healthy Young Adults., Chelsea L Deschamps, Kimberly E Connors, Matthias S Klein, Virginia L Johnsen, Jane Shearer, Hans J Vogel, Joseph M. Devaney, Heather Gordish-Dressman, Gina M Many, Whitney Barfield, Eric P. Hoffman, William E Kraus, Dustin S Hittel

Genomics and Precision Medicine Faculty Publications

Homozygosity for a premature stop codon (X) in the ACTN3 “sprinter” gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) study. Both males and females with the RR vs XX genotype achieved higher mean VO2 peak scores (47.8 ± 1.5 vs …

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.

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …