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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

Integrative Systems Biology 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 ...


Density, Abundance, And Habitat Associations Of The Inland Swamp Sparrow (Melospiza Georgiana Georgiana) In Iowa, Tyler Harms, Stephen J. Dinsmore 2017 Iowa State University

Density, Abundance, And Habitat Associations Of The Inland Swamp Sparrow (Melospiza Georgiana Georgiana) In Iowa, Tyler Harms, Stephen J. Dinsmore

Stephen J Dinsmore

Wetlands continue to decline throughout North America and the Prairie Pothole Region, thus emphasizing the importance of understanding population trends and habitat associations of wetland species to ensure effective conservation and habitat management of those species. We estimated density and abundance and evaluated habitat associations of the Inland Swamp Sparrow (Melospiza georgiana georgiana) in Iowa. We conducted standardized distance sampling surveys for Swamp Sparrows and measured habitat characteristics at 307 wetlands in two regions of Iowa in 2009 and 2010. We used Program Distance to model detection probability and estimate region-specific breeding densities of Swamp Sparrows at Iowa wetlands. We ...


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 ...


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

Mark A. Gathany, Ph.D.

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 ...


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 ...


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 ...


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, Ruixin Zhou, Kaustuv Basu, Hyman Hartman, Christopher J. Matocha, S. Kelly Sears, Hajatollah Vali, Marcelo I. Guzman 2017 University of Kentucky

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

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 ...


Computational Tools For Investigating Rna-Protein Interaction Partners, Usha K. Muppirala, Benjamin A. Lewis, Drena L. Dobbs 2017 Iowa State University

Computational Tools For Investigating Rna-Protein Interaction Partners, Usha K. Muppirala, Benjamin A. Lewis, Drena L. Dobbs

Drena Dobbs

RNA-protein interactions are important in a wide variety of cellular and developmental processes. Recently, high-throughput experiments have begun to provide valuable information about RNA partners and binding sites for many RNA-binding proteins (RBPs), but these experiments are expensive and time consuming. Thus, computational methods for predicting RNA-Protein interactions (RPIs) can be valuable tools for identifying potential interaction partners of a given protein or RNA, and for identifying likely interfacial residues in RNA-protein complexes. This review focuses on the “partner prediction” problem and summarizes available computational methods, web servers and databases that are devoted to it. New computational tools for addressing ...


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 ...


Total-Evidence Dating Under The Fossilized Birth–Death Process, Chi Zhang, Tanja Stadler, Serena Klopfstein, Tracy A. Heath, Fredrik Ronquist 2017 Swedish Museum of Natural History

Total-Evidence Dating Under The Fossilized Birth–Death Process, Chi Zhang, Tanja Stadler, Serena Klopfstein, Tracy A. Heath, Fredrik Ronquist

Tracy Heath

Bayesian total-evidence dating involves the simultaneous analysis of morphological data from the fossil record and morphological and sequence data from recent organisms, and it accommodates the uncertainty in the placement of fossils while dating the phylogenetic tree. Due to the flexibility of the Bayesian approach, total-evidence dating can also incorporate additional sources of information. Here, we take advantage of this and expand the analysis to include information about fossilization and sampling processes. Our work is based on the recently described fossilized birth–death (FBD) process, which has been used to model speciation, extinction, and fossilization rates that can vary over ...


Metnet Online: A Novel Integrated Resource For Plant Systems Biology, Yves Sucaet, Yi Wang, Eve Syrkin Wurtele 2017 Iowa State University

Metnet Online: A Novel Integrated Resource For Plant Systems Biology, Yves Sucaet, Yi Wang, Eve Syrkin Wurtele

Eve Wurtele

BackgroundPlants are important as foods, pharmaceuticals, biorenewable chemicals, fuel resources, bioremediation tools and general tools for recombinant technology. The study of plant biological pathways is advanced by easy access to integrated data sources. Today, various plant data sources are scattered throughout the web, making it increasingly complicated to build comprehensive datasets. ResultsMetNet Online is a web-based portal that provides access to a regulatory and metabolic plant pathway database. The database and portal integrate Arabidopsis, soybean (Glycine max) and grapevine (Vitis vinifera) data. Pathways are enriched with known or predicted information on sub cellular location. MetNet Online enables pathways, interactions and ...


Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal 2017 George Washington University

Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van Der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal

Integrative Systems Biology Faculty Publications

Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but the cellular basis of progressive myofiber death in DMD is not fully understood. Using two dystrophin-deficient mdx mouse models, we find that the mitochondrial dysfunction is among the earliest cellular deficits of mdx muscles. Mitochondria in dystrophic myofibers also respond poorly to sarcolemmal injury. These mitochondrial deficits reduce the ability of dystrophic muscle cell membranes to repair and are associated with a compensatory increase in dysferlin-mediated membrane repair proteins. Dysferlin deficit in mdx mice further compromises myofiber cell membrane repair and enhances the muscle pathology at an asymptomatic ...


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.


Dna Barcoding Reveals A New Morphotype Of The Sugar Kelp, Saccharina Latissima, Dallin Brimley, Zakery Ford, Travis Gould, Brandon Guerra, Emily Haggett, Ian Jones, Elyse Johnson, Ken Peterson, Matthew Prout 2017 Southern Maine Community College

Dna Barcoding Reveals A New Morphotype Of The Sugar Kelp, Saccharina Latissima, Dallin Brimley, Zakery Ford, Travis Gould, Brandon Guerra, Emily Haggett, Ian Jones, Elyse Johnson, Ken Peterson, Matthew Prout

Thinking Matters

Phytoplankton blooms follow predictable annual cycles in the Gulf of Maine, characterized by a large spring bloom and a smaller bloom in the fall. Marine phytoplankton form the foundation of primary production in Gulf of Maine waters, and thus community changes in composition, and abundance could have cascading effects on our coastal ecosystems.

We set out to monitor the community composition, diversity, and abundance of the spring micro-phytoplankton bloom, at a Friends of Casco Bay water quality monitoring site, in South Portland, Maine. The Gulf of Maine is experiencing accelerated warming rates, and this type of monitoring can aid in ...


Vamorolone, A Dissociative Steroidal Compound, Reduces Pro-Inflammatory Cytokine Expression In Glioma Cells And Increases Activity And Survival In A Murine Model Of Cortical Tumor., Elizabeth Wells, Madhuri Kambhampati, Jesse M Damsker, Heather Gordish-Dressman, Sridevi Yadavilli, Oren J Becher, Jamila Gittens, Mojca Stampar, Roger J. Packer, Javad Nazarian 2016 George Washington University

Vamorolone, A Dissociative Steroidal Compound, Reduces Pro-Inflammatory Cytokine Expression In Glioma Cells And Increases Activity And Survival In A Murine Model Of Cortical Tumor., Elizabeth Wells, Madhuri Kambhampati, Jesse M Damsker, Heather Gordish-Dressman, Sridevi Yadavilli, Oren J Becher, Jamila Gittens, Mojca Stampar, Roger J. Packer, Javad Nazarian

Integrative Systems Biology Faculty Publications

Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control. Changes in mRNA expression were assessed using the nanostring inflammatory platform. Furthermore, drug ...


Ctcf-Mediated Topological Boundaries During Development Foster Appropriate Gene Regulation, Varun Narendra, Milica Bulajic, Job Dekker, Esteban O. Mazzoni, Danny Reinberg 2016 Howard Hughes Medical Institute

Ctcf-Mediated Topological Boundaries During Development Foster Appropriate Gene Regulation, Varun Narendra, Milica Bulajic, Job Dekker, Esteban O. Mazzoni, Danny Reinberg

Program in Systems Biology Publications and Presentations

The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation. Moreover, our data suggest that CTCF-dependent boundary function can be modulated by competing forces, such as the self-assembly of polycomb domains ...


Effect Of Arginine On Oligomerization And Stability Of N-Acetylglutamate Synthase., N Haskins, A Mumo, P H Brown, Mendel Tuchman, Hiroki Morizono, L Caldovic 2016 George Washington University

Effect Of Arginine On Oligomerization And Stability Of N-Acetylglutamate Synthase., N Haskins, A Mumo, P H Brown, Mendel Tuchman, Hiroki Morizono, L Caldovic

Integrative Systems Biology Faculty Publications

N-acetylglutamate synthase (NAGS; E.C.2.3.1.1) catalyzes the formation of N-acetylglutamate (NAG) from acetyl coenzyme A and glutamate. In microorganisms and plants, NAG is the first intermediate of the L-arginine biosynthesis; in animals, NAG is an allosteric activator of carbamylphosphate synthetase I and III. In some bacteria bifunctional N-acetylglutamate synthase-kinase (NAGS-K) catalyzes the first two steps of L-arginine biosynthesis. L-arginine inhibits NAGS in bacteria, fungi, and plants and activates NAGS in mammals. L-arginine increased thermal stability of the NAGS-K from Maricaulis maris (MmNAGS-K) while it destabilized the NAGS-K from Xanthomonas campestris (XcNAGS-K). Analytical gel chromatography and ultracentrifugation ...


Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea MD, PhD, Cristian G. Bologa PhD, Subramani Mani MD, PhD, Oleg Ursu PhD 2016 University of New Mexico School of Medicine

Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea Md, Phd, Cristian G. Bologa Phd, Subramani Mani Md, Phd, Oleg Ursu Phd

Biomedical Sciences ETDs

The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.

The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this ...


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