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Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley 2017 George Washington University

Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley

Genomics and Precision Medicine Faculty Publications

Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM. By disruption of phosphofurin acidic cluster sorting protein 2 (PACS-2), mitofusins (Mfn1/2), and dynamin related protein 1 ...


The Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Rs4340 Associates With Habitual Physical Activity Among European American Adults., Michael Bruneau, Theodore J Angelopoulos, Paul Gordon, Niall Moyna, Paul Visich, Robert Zoeller, Rick Seip, Stephen Bilbie, Paul Thompson, Joseph Devaney, Heather Gordish-Dressman, Eric Hoffman, Linda S Pescatello 2017 George Washington University

The Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Rs4340 Associates With Habitual Physical Activity Among European American Adults., Michael Bruneau, Theodore J Angelopoulos, Paul Gordon, Niall Moyna, Paul Visich, Robert Zoeller, Rick Seip, Stephen Bilbie, Paul Thompson, Joseph Devaney, Heather Gordish-Dressman, Eric Hoffman, Linda S Pescatello

Genomics and Precision Medicine Faculty Publications

BACKGROUND: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (ACE DIP) accounts for half of the variability in plasma ACE concentrations. ACE has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the ACE DIP on physical activity among 461 European Americans.

METHODS: Subjects completed the Paffenbarger Physical Activity Questionnaire for weekly walking distance. Multivariate analysis of covariance (MANCOVA) tested log-transformed differences in weekly walking distance among ACE DIP genotypes (II, ID, DD) with gender as a fixed factor, and age ...


The Mayfly Newsletter, Donna J. Giberson 2017 The Permanent Committee of the International Conferences on Ephemeroptera

The Mayfly Newsletter, Donna J. Giberson

The Mayfly Newsletter

No abstract provided.


Self-Consistent Theory Of Transcriptional Control In Complex Regulatory Architectures, Jasper Landman, Robert C. Brewster, Franz M. Weinert, Rob Phillips, Willem K. Kegel 2017 Utrecht University

Self-Consistent Theory Of Transcriptional Control In Complex Regulatory Architectures, Jasper Landman, Robert C. Brewster, Franz M. Weinert, Rob Phillips, Willem K. Kegel

Program in Systems Biology Publications and Presentations

Individual regulatory proteins are typically charged with the simultaneous regulation of a battery of different genes. As a result, when one of these proteins is limiting, competitive effects have a significant impact on the transcriptional response of the regulated genes. Here we present a general framework for the analysis of any generic regulatory architecture that accounts for the competitive effects of the regulatory environment by isolating these effects into an effective concentration parameter. These predictions are formulated using the grand-canonical ensemble of statistical mechanics and the fold-change in gene expression is predicted as a function of the number of transcription ...


Strand-Specific Libraries For High Throughput Rna Sequencing (Rna-Seq) Prepared Without Poly(A) Selection, Zhao Zhang, William E. Theurkauf, Zhiping Weng, Phillip D. Zamore 2017 University of Massachusetts Medical School

Strand-Specific Libraries For High Throughput Rna Sequencing (Rna-Seq) Prepared Without Poly(A) Selection, Zhao Zhang, William E. Theurkauf, Zhiping Weng, Phillip D. Zamore

Zhao Zhang

BACKGROUND: High throughput DNA sequencing technology has enabled quantification of all the RNAs in a cell or tissue, a method widely known as RNA sequencing (RNA-Seq). However, non-coding RNAs such as rRNA are highly abundant and can consume >70% of sequencing reads. A common approach is to extract only polyadenylated mRNA; however, such approaches are blind to RNAs with short or no poly(A) tails, leading to an incomplete view of the transcriptome. Another challenge of preparing RNA-Seq libraries is to preserve the strand information of the RNAs. DESIGN: Here, we describe a procedure for preparing RNA-Seq libraries from 1 ...


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 2017 Marshall University

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

Qun Wang

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 ...


African-American Esophageal Squamous Cell Carcinoma Expression Profile Reveals Dysregulation Of Stress Response And Detox Networks., Hayriye Verda Erkizan, Kory Johnson, Svetlana Ghimbovschi, Deepa Karkera, Gregory Trachiotis, Houtan Adib, Eric P Hoffman, Robert G Wadleigh 2017 George Washington University

African-American Esophageal Squamous Cell Carcinoma Expression Profile Reveals Dysregulation Of Stress Response And Detox Networks., Hayriye Verda Erkizan, Kory Johnson, Svetlana Ghimbovschi, Deepa Karkera, Gregory Trachiotis, Houtan Adib, Eric P Hoffman, Robert G Wadleigh

Genomics and Precision Medicine Faculty Publications

BACKGROUND: Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups.

METHODS: To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues.

RESULTS ...


Crispr/Cas9-Mediated Genome Editing Induces Exon Skipping By Alternative Splicing Or Exon Deletion, Haiwei Mou, Jordan L. Smith, Lingtao Peng, Jill Moore, Xiao-Ou Zhang, Chun-Qing Song, Ankur Sheel, Deniz M. Ozata, Yingxiang Li, Charles P. Emerson Jr., Erik J. Sontheimer, Melissa J. Moore, Zhiping Weng, Wen Xue 2017 University of Massachusetts Medical School

Crispr/Cas9-Mediated Genome Editing Induces Exon Skipping By Alternative Splicing Or Exon Deletion, Haiwei Mou, Jordan L. Smith, Lingtao Peng, Jill Moore, Xiao-Ou Zhang, Chun-Qing Song, Ankur Sheel, Deniz M. Ozata, Yingxiang Li, Charles P. Emerson Jr., Erik J. Sontheimer, Melissa J. Moore, Zhiping Weng, Wen Xue

Program in Bioinformatics and Integrative Biology Publications and Presentations

CRISPR is widely used to disrupt gene function by inducing small insertions and deletions. Here, we show that some single-guide RNAs (sgRNAs) can induce exon skipping or large genomic deletions that delete exons. For example, CRISPR-mediated editing of beta-catenin exon 3, which encodes an autoinhibitory domain, induces partial skipping of the in-frame exon and nuclear accumulation of beta-catenin. A single sgRNA can induce small insertions or deletions that partially alter splicing or unexpected larger deletions that remove exons. Exon skipping adds to the unexpected outcomes that must be accounted for, and perhaps taken advantage of, in CRISPR experiments.


Improving Reproducibility Of Phenotypic Assessments In The Dyw Mouse Model Of Laminin-Α2 Related Congenital Muscular Dystrophy., Raffaella Willmann, Heather Gordish-Dressman, Sarina Meinen, Markus A Rüegg, Qing Yu, Kanneboyina Nagaraju, +several additional authors 2017 George Washington University

Improving Reproducibility Of Phenotypic Assessments In The Dyw Mouse Model Of Laminin-Α2 Related Congenital Muscular Dystrophy., Raffaella Willmann, Heather Gordish-Dressman, Sarina Meinen, Markus A Rüegg, Qing Yu, Kanneboyina Nagaraju, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Laminin-α2 related Congenital Muscular Dystrophy (LAMA2-CMD) is a progressive muscle disease caused by partial or complete deficiency of laminin-211, a skeletal muscle extracellular matrix protein. In the last decade, basic science research has queried underlying disease mechanisms in existing LAMA2-CMD murine models and identified possible clinical targets and pharmacological interventions. Experimental rigor in preclinical studies is critical to efficiently and accurately quantify both negative and positive results, degree of efficiency of potential therapeutics and determine whether to move a compound forward for additional preclinical testing. In this review, we compare published available data measured to assess three common parameters in ...


Shelterin Components Mediate Genome Reorganization In Response To Replication Stress, Takeshi Mizuguchi, Nitika Taneja, Emiko Matsuda, Jon-Matthew Belton, Peter FitzGerald, Job Dekker, Shiv I. Grewal S 2017 National Institutes of Health

Shelterin Components Mediate Genome Reorganization In Response To Replication Stress, Takeshi Mizuguchi, Nitika Taneja, Emiko Matsuda, Jon-Matthew Belton, Peter Fitzgerald, Job Dekker, Shiv I. Grewal S

Program in Systems Biology Publications and Presentations

The dynamic nature of genome organization impacts critical nuclear functions including the regulation of gene expression, replication, and DNA damage repair. Despite significant progress, the mechanisms responsible for reorganization of the genome in response to cellular stress, such as aberrant DNA replication, are poorly understood. Here, we show that fission yeast cells carrying a mutation in the DNA-binding protein Sap1 show defects in DNA replication progression and genome stability and display extensive changes in genome organization. Chromosomal regions such as subtelomeres that show defects in replication progression associate with the nuclear envelope in sap1 mutant cells. Moreover, high-resolution, genome-wide chromosome ...


Systems Immunology Of Diabetes-Tuberculosis Comorbidity Reveals Signatures Of Disease Complications, Cesar A. Prada-Medina, Kiyoshi F. Fukutani, Nathella Pavan Kumar, Leonardo Gil-Santana, Subash Babu, Flavio Lichtenstein, Kim West, Shanmugam Sivakumar, Pradeep A. Menon, Vijay Viswanathan, Bruno B. Andrade, Helder I. Nakaya, Hardy Kornfeld 2017 University of São Paulo, Brazil

Systems Immunology Of Diabetes-Tuberculosis Comorbidity Reveals Signatures Of Disease Complications, Cesar A. Prada-Medina, Kiyoshi F. Fukutani, Nathella Pavan Kumar, Leonardo Gil-Santana, Subash Babu, Flavio Lichtenstein, Kim West, Shanmugam Sivakumar, Pradeep A. Menon, Vijay Viswanathan, Bruno B. Andrade, Helder I. Nakaya, Hardy Kornfeld

Open Access Articles

Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM. Neutrophil count correlated with the molecular degree of perturbation, especially in TBDM patients. Body mass index ...


B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips 2017 Seton Hall University

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory ...


Comparison Of The Regulatory Dynamics Of Related Small Gene Regulatory Networks That Control The Response To Cold Shock In Saccharomyces Cerevisiae, Natalie Williams 2017 Loyola Marymount University

Comparison Of The Regulatory Dynamics Of Related Small Gene Regulatory Networks That Control The Response To Cold Shock In Saccharomyces Cerevisiae, Natalie Williams

Honors Thesis

The Dahlquist Lab investigates the global, transcriptional response of Sacchromyces cerevisiae, baker’s yeast, to the environmental stress of cold shock, using DNA microarrays for the wild type strain and strains deleted for a particular regulatory transcription factor. Gene regulatory networks (GRNs) consist of transcription factors (TF), genes, and the regulatory connections between them that control the resulting mRNA and protein expression levels. We use mathematical modeling to determine the dynamics of the GRN controlling the cold shock response to determine the relative influence of each transcription factor in the network. A family of GRNs has been derived from the ...


Regeneration Of Imperiled Hardwoods In The Eastern United States, Joshua J. Granger 2017 University of Tennessee, Knoxville

Regeneration Of Imperiled Hardwoods In The Eastern United States, Joshua J. Granger

Doctoral Dissertations

Our ability to successfully promote forest stand health and facilitate species under the threat of extinction will hinge on our ability to identify species regeneration requirements in an ever-changing environment. In the first chapter of this dissertation, I address what is known about the nature of threatened and imperiled hardwoods in the eastern United States, and in doing so, I identify several large knowledge gaps in current potentials and methodologies for regenerating them. In my second chapter, I use recent data from the United States Forest Service, Forest Inventory and Analysis program (FIA) to quantify ash regeneration counts across FIA ...


Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites 2017 The University of Western Ontario

Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites

Electronic Thesis and Dissertation Repository

Cellular division is primarily controlled at the G1 to S-phase transition of the cell cycle by the retinoblastoma tumor-suppressor protein (pRB). The ability of pRB to restrict S-phase entry is primarily attributed to the repression of E2F transcription factors required to upregulate cell cycle target genes necessary for cellular division. Interestingly, while pRB is disrupted in the vast majority of human cancers, mutations typically target upstream regulators of pRB leading to inactivation through hyperphosphorylation. The rarity of direct pRB mutations suggests that the regulation of the cell cycle by pRB may involve additional mechanisms outside of E2F repression, as this ...


Effect Of Transcription Factor Resource Sharing On Gene Expression Noise, Dipjyoti Das, Supravat Dey, Robert C. Brewster, Sandeep Choubey 2017 Yale University

Effect Of Transcription Factor Resource Sharing On Gene Expression Noise, Dipjyoti Das, Supravat Dey, Robert C. Brewster, Sandeep Choubey

Program in Systems Biology Publications and Presentations

Gene expression is intrinsically a stochastic (noisy) process with important implications for cellular functions. Deciphering the underlying mechanisms of gene expression noise remains one of the key challenges of regulatory biology. Theoretical models of transcription often incorporate the kinetics of how transcription factors (TFs) interact with a single promoter to impact gene expression noise. However, inside single cells multiple identical gene copies as well as additional binding sites can compete for a limiting pool of TFs. Here we develop a simple kinetic model of transcription, which explicitly incorporates this interplay between TF copy number and its binding sites. We show ...


Spatial And Temporal Variability Of Water Quality Parameters In Cedar Lake (Cedarville, Ohio), Laura A. Cashman, William A. Smith, Shannon L. Swicker, Abigail L. Williams, Mark A. Gathany 2017 Cedarville University

Spatial And Temporal Variability Of Water Quality Parameters In Cedar Lake (Cedarville, Ohio), Laura A. Cashman, William A. Smith, Shannon L. Swicker, Abigail L. Williams, Mark A. Gathany

The Research and Scholarship Symposium

Cedar Lake is a man-made lake that is central to Cedarville University’s campus. This focal point of the campus is a source of aesthetic appeal and beauty of Cedarville University. The lake ranges in depth from 0.6-3.7m, is 140m by 150m across, an approximate volume of 40,000 m3 and demonstrates normal capabilities to support fish and other life. There is, however, some concern over Cedar Lake’s level of productivity as undesirable algae blooms are common during warmer months. In October and November 2016 we began to assess the spatial and temporal variability of water ...


Catalyzed Synthesis Of Zinc Clays By Prebiotic Central Metabolites, Marcelo I. Guzman, Ruixin Zhou, Kaustuv Basu, Hyman Hartman, Christopher J. Matocha, S. Kelly Sears, Hajatollah Vali 2017 University of Kentucky

Catalyzed Synthesis Of Zinc Clays By Prebiotic Central Metabolites, Marcelo I. Guzman, Ruixin Zhou, Kaustuv Basu, Hyman Hartman, Christopher J. Matocha, S. Kelly Sears, Hajatollah Vali

Chemistry Faculty Publications

How primordial metabolic networks such as the reverse tricarboxylic acid (rTCA) cycle and clay mineral catalysts coevolved remains a mystery in the puzzle to understand the origin of life. While prebiotic reactions from the rTCA cycle were accomplished via photochemistry on semiconductor minerals, the synthesis of clays was demonstrated at low temperature and ambient pressure catalyzed by oxalate. Herein, the crystallization of clay minerals is catalyzed by succinate, an example of a photoproduced intermediate from central metabolism. The experiments connect the synthesis of sauconite, a model for clay minerals, to prebiotic photochemistry. We report the temperature, pH, and concentration dependence ...


Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto 2017 George Washington University

Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto

GW Research Days 2016 - Present

While BRAF is among the most well-established oncogenes in human cancers, more recently it has garnered attention for its role in suppressing antitumor immunity, especially in melanoma. Because tumor-infiltrating lymphocyte (TIL) density is strongly prognostic in colorectal cancer (CRC)7, we decided to investigate the connection between TIL density and the BRAF-activating V600E mutation in CRC.

We used ESTIMATE to quantify immune infiltrate in samples from the TCGA colon adenocarcinoma (COAD) dataset (n = 216). This is an algorithm that uses the gene-expression signature of 141 immune-related genes to infer the presence of immune cells in the tumor infiltrate. COAD samples ...


Revbayes: Bayesian Phylogenetic Inference Using Graphical Models And An Interactive Model-Specification Language, Sebastian Höhna, Michael J. Landis, Tracy A. Heath, Nicolas Lartillot, Brian R. Moore, John P. Huelsenbeck, Fredrik Ronquist 2017 University of California, Berkeley

Revbayes: Bayesian Phylogenetic Inference Using Graphical Models And An Interactive Model-Specification Language, Sebastian Höhna, Michael J. Landis, Tracy A. Heath, Nicolas Lartillot, Brian R. Moore, John P. Huelsenbeck, Fredrik Ronquist

Tracy Heath

Programs for Bayesian inference of phylogeny currently implement a unique and fixed suite of models. Consequently, users of these software packages are simultaneously forced to use a number of programs for a given study, while also lacking the freedom to explore models that have not been implemented by the developers of those programs. We developed a new open-source software package, RevBayes, to address these problems. RevBayes is entirely based on probabilistic graphical models, a powerful generic framework for specifying and analyzing statistical models. Phylogenetic-graphical models can be specified interactively in RevBayes, piece by piece, using a new succinct and intuitive ...


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