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Calmodulation Meta-Analysis: Predicting Calmodulin Binding Via Canonical Motif Clustering, Karen Mruk, Brian M. Farley, Alan W. Ritacco, William R. Kobertz 2014 University of Massachusetts Medical School

Calmodulation Meta-Analysis: Predicting Calmodulin Binding Via Canonical Motif Clustering, Karen Mruk, Brian M. Farley, Alan W. Ritacco, William R. Kobertz

Biochemistry and Molecular Pharmacology Publications and Presentations

The calcium-binding protein calmodulin (CaM) directly binds to membrane transport proteins to modulate their function in response to changes in intracellular calcium concentrations. Because CaM recognizes and binds to a wide variety of target sequences, identifying CaM-binding sites is difficult, requiring intensive sequence gazing and extensive biochemical analysis. Here, we describe a straightforward computational script that rapidly identifies canonical CaM-binding motifs within an amino acid sequence. Analysis of the target sequences from high resolution CaM-peptide structures using this script revealed that CaM often binds to sequences that have multiple overlapping canonical CaM-binding motifs. The addition of a positive charge discriminator ...


Increased 5-Hydroxymethylcytosine And Decreased 5-Methylcytosine Are Indicators Of Global Epigenetic Dysregulation In Diffuse Intrinsic Pontine Glioma, Sama Ahsan, Eric H. Raabe, Michael C. Haffner, Ajay Vaghasia, Katherine E. Warren, Martha Quezado, Leomar Y. Ballester, Javad Nazarian, Charles G. Eberhart, Fausto J. Rodriguez 2014 Himmelfarb Health Sciences Library, The George Washington University

Increased 5-Hydroxymethylcytosine And Decreased 5-Methylcytosine Are Indicators Of Global Epigenetic Dysregulation In Diffuse Intrinsic Pontine Glioma, Sama Ahsan, Eric H. Raabe, Michael C. Haffner, Ajay Vaghasia, Katherine E. Warren, Martha Quezado, Leomar Y. Ballester, Javad Nazarian, Charles G. Eberhart, Fausto J. Rodriguez

Integrative Systems Biology Faculty Publications

Introduction

Diffuse intrinsic pontine glioma (DIPG) is a malignant pediatric brain tumor associated with dismal outcome. Recent high-throughput molecular studies have shown a high frequency of mutations in histone-encoding genes (H3F3A and HIST1B) and distinctive epigenetic alterations in these tumors. Epigenetic alterations described in DIPG include global DNA hypomethylation. In addition to the generally repressive methylcytosine DNA alteration, 5-hydroxymethylation of cytosine (5hmC) is recognized as an epigenetic mark associated with active chromatin. We hypothesized that in addition to alterations in DNA methylation, that there would be changes in 5hmC. To test this hypothesis, we performed immunohistochemical studies to compare epigenetic ...


Optimal Experimental Design For Parameter Identification And Model Selection, René Schenkendorf 2014 SelectedWorks

Optimal Experimental Design For Parameter Identification And Model Selection, René Schenkendorf

René Schenkendorf

No abstract provided.


Multiple Transcription Factors Directly Regulate Hox Gene Lin-39 Expression In Ventral Hypodermal Cells Of The C. Elegans Embryo And Larva, Including The Hypodermal Fate Regulators Lin-26 And Elt-6, Wan-Ju Liu, John S. Reece-Hoyes, Albertha J. M. Walhout, David M. Eisenmann 2014 University of Massachusetts Medical School

Multiple Transcription Factors Directly Regulate Hox Gene Lin-39 Expression In Ventral Hypodermal Cells Of The C. Elegans Embryo And Larva, Including The Hypodermal Fate Regulators Lin-26 And Elt-6, Wan-Ju Liu, John S. Reece-Hoyes, Albertha J. M. Walhout, David M. Eisenmann

Program in Systems Biology Publications and Presentations

BACKGROUND: Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo.

RESULTS: We used the ...


The Equitable Contributions Of Environment, Management And Restoration Status On Grassland Diversity And Composition, RaeAnn C. Powers 2014 University of Nebraska - Lincoln

The Equitable Contributions Of Environment, Management And Restoration Status On Grassland Diversity And Composition, Raeann C. Powers

Dissertations and Theses in Biological Sciences

Plant composition is controlled by a combination of environmental, biotic, historical and management factors. Although there has been much focus on restoring grassland diversity, it is unclear which factors and/or interactions of factors are constraining diversity in grasslands and the relative influences of different factors. We measured soil fertility, soil texture, grazing intensity, fire frequency and plant cover in 694 plots, located within 33 remnant and restored fields in managed grasslands in the central Great Plains. Using univariate (general linear model) and multivariate (PERMANOVA) analyses, we identified significant factors and their relative contributions to plant richness, evenness, floristic quality ...


Defining Functional Dna Elements In The Human Genome, Manolis Kellis, Barbara Wold, Michael P. Snyder, Bradley E. Bernstein, Anshul Kundaje, Georgi K. Marinov, Lucas D. Ward, Job Dekker, Zhiping Weng, Ross C. Hardison, ENCODE Project Consortium 2014 University of Massachusetts Medical School

Defining Functional Dna Elements In The Human Genome, Manolis Kellis, Barbara Wold, Michael P. Snyder, Bradley E. Bernstein, Anshul Kundaje, Georgi K. Marinov, Lucas D. Ward, Job Dekker, Zhiping Weng, Ross C. Hardison, Encode Project Consortium

Program in Systems Biology Publications and Presentations

With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily ...


High Hiv Incidence In The Postpartum Period Sustains Vertical Transmission In Settings With Generalized Epidemics: A Cohort Study In Southern Mozambique, Caroline De Schacht, Nedia Mabunda, Orlando C. Ferreira Jr., Nalia Ismael, Nurbai Calu, Iolanda Santos, Heather J. Hoffman, Catharina Alons, Laura Guay, Ilesh V. Jani 2014 Himmelfarb Health Sciences Library, The George Washington University

High Hiv Incidence In The Postpartum Period Sustains Vertical Transmission In Settings With Generalized Epidemics: A Cohort Study In Southern Mozambique, Caroline De Schacht, Nedia Mabunda, Orlando C. Ferreira Jr., Nalia Ismael, Nurbai Calu, Iolanda Santos, Heather J. Hoffman, Catharina Alons, Laura Guay, Ilesh V. Jani

Integrative Systems Biology Faculty Publications

Introduction: Acute infection with HIV in the postpartum period results in a high risk of vertical transmission through breastfeeding. A study was done to determine the HIV incidence rate and associated risk factors among postpartum women in Southern Mozambique, where HIV prevalence among pregnant women is 21%.

Methods: A prospective cohort study was conducted in six rural health facilities in Gaza and Maputo provinces from March 2008 to July 2011. A total of 1221 women who were HIV-negative on testing at delivery or within two months postpartum were recruited and followed until 18 months postpartum. HIV testing, collection of dried ...


Expression Pattern And Biochemical Properties Of Zebrafish N-Acetylglutamate Synthase, Ljubica Caldovic, Nantaporn Haskins, Amy Mumo, Himani Majumdar, Mary Pinter, Mendel Tuchman, Alison Krufka 2014 Himmelfarb Health Sciences Library, The George Washington University

Expression Pattern And Biochemical Properties Of Zebrafish N-Acetylglutamate Synthase, Ljubica Caldovic, Nantaporn Haskins, Amy Mumo, Himani Majumdar, Mary Pinter, Mendel Tuchman, Alison Krufka

Integrative Systems Biology Faculty Publications

The urea cycle converts ammonia, a waste product of protein catabolism, into urea. Because fish dispose ammonia directly into water, the role of the urea cycle in fish remains unknown. Six enzymes, N-acetylglutamate synthase (NAGS), carbamylphosphate synthetase III, ornithine transcarbamylase, argininosuccinate synthase, argininosuccinate lyase and arginase 1, and two membrane transporters, ornithine transporter and aralar, comprise the urea cycle. The genes for all six enzymes and both transporters are present in the zebrafish genome. NAGS (EC 2.3.1.1) catalyzes the formation of N-acetylglutamate from glutamate and acetyl coenzyme A and in zebrafish is partially inhibited by L-arginine. NAGS ...


Transcription Factor Binding To Caenorhabditis Elegans First Introns Reveals Lack Of Redundancy With Gene Promoters, Juan I. Fuxman Bass, Alex M. Tamburino, Akihiro Mori, Nathan Beittel, Matthew T. Weirauch, John S. Reece-Hoyes, Albertha J. M. Walhout 2014 University of Massachusetts Medical School

Transcription Factor Binding To Caenorhabditis Elegans First Introns Reveals Lack Of Redundancy With Gene Promoters, Juan I. Fuxman Bass, Alex M. Tamburino, Akihiro Mori, Nathan Beittel, Matthew T. Weirauch, John S. Reece-Hoyes, Albertha J. M. Walhout

Program in Systems Biology Publications and Presentations

Gene expression is controlled through the binding of transcription factors (TFs) to regulatory genomic regions. First introns are longer than other introns in multiple eukaryotic species and are under selective constraint. Here we explore the importance of first introns in TF binding in the nematode Caenorhabditis elegans by combining computational predictions and experimentally derived TF-DNA interaction data. We found that first introns of C. elegans genes, particularly those for families enriched in long first introns, are more conserved in length, have more conserved predicted TF interactions and are bound by more TFs than other introns. We detected a significant positive ...


Dysferlin Regulates Cell Membrane Repair By Facilitating Injury-Triggered Acid Sphingomyelinase Secretion, Aurelia Defour, Jack H. Van der Meulen, Rujuta R. Bhatt, Anne Bigot, R. Bashir, Kanneboyina Nagaraju, Jyoti K. Jaiswal 2014 Himmelfarb Health Sciences Library, The George Washington University

Dysferlin Regulates Cell Membrane Repair By Facilitating Injury-Triggered Acid Sphingomyelinase Secretion, Aurelia Defour, Jack H. Van Der Meulen, Rujuta R. Bhatt, Anne Bigot, R. Bashir, Kanneboyina Nagaraju, Jyoti K. Jaiswal

Integrative Systems Biology Faculty Publications

Dysferlin deficiency compromises the repair of injured muscle, but the underlying cellular mechanism remains elusive. To study this phenomenon, we have developed mouse and human myoblast models for dysferlinopathy. These dysferlinopathic myoblasts undergo normal differentiation but have a deficit in their ability to repair focal injury to their cell membrane. Imaging cells undergoing repair showed that dysferlin-deficit decreased the number of lysosomes present at the cell membrane, resulting in a delay and reduction in injury-triggered lysosomal exocytosis. We find repair of injured cells does not involve formation of intracellular membrane patch through lysosome–lysosome fusion; instead, individual lysosomes fuse with ...


Stellaris Fish Workshop Gadph And Dapi Z-Series, George McNamara 2013 The University of Texas

Stellaris Fish Workshop Gadph And Dapi Z-Series, George Mcnamara

George McNamara

Stellaris FISH workshop GADPH and DAPI Z-series at MD Anderson Cancer Center, Houston, TX.

The zip file contains raw and GPU deconvolved image data from a workshop Biosearch Technologies conducted for MDACC researchers in December 2013. Image data was acquired on a Leica DMI6000 microscope with Lumencor SOLA light engine, DAPI and Cy5 filter cubes, Hamamatsu ORCA FLASH4.0 sCMOS camera (500 ms exposure time per plane for Quasar 670).

Pixel size 100 nm XY.

Z-step size 200 nm.

32 planes (power of 2 is optimal for GPU deconvolution). With 500 ms exposure time, the Quasar 670 GADPH FISH probes ...


Cohesin-Based Chromatin Interactions Enable Regulated Gene Expression Within Pre-Existing Architectural Compartments, Vlad Seitan, Andre Faure, Ye Zhan, Rachel Patton McCord, Bryan R. Lajoie, Elizabeth Ing-Simmons, Boris Lenhard, Luca Giorgetti, Edith Heard, Amanda Fisher, Paul Flicek, Job Dekker, Matthias Merkenschlager 2013 University of Massachusetts Medical School

Cohesin-Based Chromatin Interactions Enable Regulated Gene Expression Within Pre-Existing Architectural Compartments, Vlad Seitan, Andre Faure, Ye Zhan, Rachel Patton Mccord, Bryan R. Lajoie, Elizabeth Ing-Simmons, Boris Lenhard, Luca Giorgetti, Edith Heard, Amanda Fisher, Paul Flicek, Job Dekker, Matthias Merkenschlager

Program in Systems Biology Publications and Presentations

Chromosome conformation capture approaches have shown that interphase chromatin is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized topological domains. This compartmentalization is thought to facilitate the matching of genes and regulatory elements, but its precise function and mechanistic basis remain unknown. Cohesin controls chromosome topology to enable DNA repair and chromosome segregation in cycling cells. In addition, cohesin associates with active enhancers and promoters and with CTCF to form long-range interactions important for gene regulation. Although these findings suggest an important role for cohesin in genome organization, this role has not been assessed on a global scale. Unexpectedly, we ...


Flexible Ordering Of Antibody Class Switch And V(D)J Joining During B-Cell Ontogeny, Satyendra Kumar, Robert Wuerffel, Ikbel Achour, Bryan R. Lajoie, Ranjan Sen, Job Dekker, Ann J. Feeney, Amy L. Kenter 2013 University of Massachusetts Medical School

Flexible Ordering Of Antibody Class Switch And V(D)J Joining During B-Cell Ontogeny, Satyendra Kumar, Robert Wuerffel, Ikbel Achour, Bryan R. Lajoie, Ranjan Sen, Job Dekker, Ann J. Feeney, Amy L. Kenter

Program in Systems Biology Publications and Presentations

V(D)J joining is mediated by RAG recombinase during early B-lymphocyte development in the bone marrow (BM). Activation-induced deaminase initiates isotype switching in mature B cells of secondary lymphoid structures. Previous studies questioned the strict ontological partitioning of these processes. We show that pro-B cells undergo robust switching to a subset of immunoglobulin H (IgH) isotypes. Chromatin studies reveal that in pro-B cells, the spatial organization of the Igh locus may restrict switching to this subset of isotypes. We demonstrate that in the BM, V(D)J joining and switching are interchangeably inducible, providing an explanation for the hyper-IgE ...


Conditional Expression Of Tgf-Β1 In Skeletal Muscles Causes Endomysial Fibrosis And Myofibers Atrophy, Jigna Narola, Sachchida Nand Pandey, Adam Glick, Yi-Wen Chen 2013 Himmelfarb Health Sciences Library, The George Washington University

Conditional Expression Of Tgf-Β1 In Skeletal Muscles Causes Endomysial Fibrosis And Myofibers Atrophy, Jigna Narola, Sachchida Nand Pandey, Adam Glick, Yi-Wen Chen

Integrative Systems Biology Faculty Publications

To study the effects of transforming growth factor beta 1 (TGF-β1) on fibrosis and failure of regeneration of skeletal muscles, we generated a tet-repressible muscle-specific TGF-β1transgenic mouse in which expression of TGF-β1 is controlled by oral doxycycline. The mice developed muscle weakness and atrophy after TGF-β1 over-expression. We defined the group of mice that showed phenotype within 2 weeks as early onset (EO) and the rest as late onset (LO), which allowed us to further examine phenotypic differences between the groups. While only mice in the EO group showed significant muscle weakness, pathological changes including endomysial fibrosis and smaller ...


Leica Microscope Gpu Deconvolution Stellaris Fish Dataset #1, George McNamara 2013 The University of Texas

Leica Microscope Gpu Deconvolution Stellaris Fish Dataset #1, George Mcnamara

George McNamara

McNamara 20131101Fri Leica widefield microscope CUDA Deconvolution Stellaris FISH probe cultured cells dataset #1.zip

A text file in the zip archive has experiment details. I am posting this online so that researchers - whether academic or commercial - can evaluate the acquired data, the Bruce and Butte 2013 Optics Express ( http://www.opticsinfobase.org/oe/fulltext.cfm?uri=oe-21-4-4766 ) deconvolution result (note: I may not have used optimal settings), and to compare these deconvolution results to other methods. If anyone generates alternative spatial deconvolution output, such as from: * SVI Huygens * Media Cy AutoQuant * Agard's ER-Decon (Arigovindan 2013 PNAS) * Vicidomini SGP ...


The Envenoming Pandemic And The Misguided Views Of Snakes: Developing Sustainable Relationships Between Native Poisonous Snakes Of India And The Citizens Of Maharashtra Through The Use Of The Irula Model., Destiny Villanueva 2013 California Polytechnic State University

The Envenoming Pandemic And The Misguided Views Of Snakes: Developing Sustainable Relationships Between Native Poisonous Snakes Of India And The Citizens Of Maharashtra Through The Use Of The Irula Model., Destiny Villanueva

Animal Science

Due to its vast population and general negative consensus regarding snakes, India is notorious for having more snakebite incidents than any other country. Snakes are simultaneously revered and feared in Indian religion and culture. This stigma is perpetuated through propaganda, family beliefs, and innate fears of snakes.These stigmas are more pronounced within rural areas, such as the region of Mahad within the state of Maharshtra. Envenoming is endemic in these areas, and others like them. The World Health Organization identified envenoming as one of the most neglected tropical diseases of the 21st century (Nature India, 2013). Additionally, both nonvenomous ...


Vbp15, A Novel Anti-Inflammatory And Membrane-Stabilizer, Improves Muscular Dystrophy Without Side Effects, Christopher R. Heier, Jesse M. Damsker, Qing Yu, Blythe C. Dillingham, Tony Huynh, Heather A. Gordish-Dressman, Jyoti K. Jaiswal, Eric P. Hoffman, Kanneboyina Nagaraju, +15 additional authors 2013 Himmelfarb Health Sciences Library, The George Washington University

Vbp15, A Novel Anti-Inflammatory And Membrane-Stabilizer, Improves Muscular Dystrophy Without Side Effects, Christopher R. Heier, Jesse M. Damsker, Qing Yu, Blythe C. Dillingham, Tony Huynh, Heather A. Gordish-Dressman, Jyoti K. Jaiswal, Eric P. Hoffman, Kanneboyina Nagaraju, +15 Additional Authors

Integrative Systems Biology Faculty Publications

Absence of dystrophin makes skeletal muscle more susceptible to injury, resulting in breaches of the plasma membrane and chronic inflammation in Duchenne muscular dystrophy (DMD). Current management by glucocorticoids has unclear molecular benefits and harsh side effects. It is uncertain whether therapies that avoid hormonal stunting of growth and development, and/or immunosuppression, would be more or less beneficial. Here, we discover an oral drug with mechanisms that provide efficacy through anti-inflammatory signaling and membrane-stabilizing pathways, independent of hormonal or immunosuppressive effects. We find VBP15 protects and promotes efficient repair of skeletal muscle cells upon laser injury, in opposition to ...


On Using Network Theory To Identify Significant Elements In Protein-Protein Interaction Networks, Rohan Khazanchi 2013 Washington University in St. Louis

On Using Network Theory To Identify Significant Elements In Protein-Protein Interaction Networks, Rohan Khazanchi

Undergraduate Research Symposium Posters & Abstracts

Network theory has been used by researchers for multiple purposes in the past to model biological data as well as social, transportation, business, and many other types of data in various domains. When analyzing a network that represents protein-protein interactions (PPIs), identifying elements of significant importance and biological-relevance is critical. In this work, we hypothesize that there is a high correlation between structural properties associated with elements in a PPI network and their biological significance. We identify special elements, such as hubs and driver nodes, as well as special sub-networks, such as dense clusters in the obtained biological networks. We ...


Transformations In Matter And Energy: Student Learning And Inquiry To Inform Teaching, Jenny Dauer 2013 University of Nebraska - Lincoln

Transformations In Matter And Energy: Student Learning And Inquiry To Inform Teaching, Jenny Dauer

DBER Speaker Series

Learning progressions are descriptions of increasing levels of sophistication of student reasoning about a topic based on empirical evidence. Our learning progression framework about student explanations of carbon-transforming processes (e.g. photosynthesis, cellular respiration) describes how student’s interconnected and mutually supporting ideas and practices are deeply embedded in discourse at all levels of achievement. My research is in two areas: 1) applying the learning progression framework for student explanations of carbon-transforming processes to describe the most productive pathways for student learning, 2) extending the research to student reasoning during inquiry activities about carbon-transforming processes. One finding is that students ...


An Exploration Of Heat Tolerance In Mice Utilizing Mrna And Microrna Expression Analysis, Islam Aminul, Patricia A. Deuster, Joseph M. Devaney, Svetlana Ghimbovschi, Yifan Chen 2013 Himmelfarb Health Sciences Library, The George Washington University

An Exploration Of Heat Tolerance In Mice Utilizing Mrna And Microrna Expression Analysis, Islam Aminul, Patricia A. Deuster, Joseph M. Devaney, Svetlana Ghimbovschi, Yifan Chen

Integrative Systems Biology Faculty Publications

Background

Individuals who rapidly develop hyperthermia during heat exposure (heat-intolerant) are vulnerable to heat associated illness and injury. We recently reported that heat intolerant mice exhibit complex alterations in stress proteins in response to heat exposure. In the present study, we further explored the role of genes and molecular networks associated with heat tolerance in mice.

Methodology

Heat-induced physiological and biochemical changes were assessed to determine heat tolerance levels in mice. We performed RNA and microRNA expression profiling on mouse gastrocnemius muscle tissue samples to determine novel biological pathways associated with heat tolerance.

Principal Findings

Mice (n = 18) were assigned ...


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