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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 ...


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 ...


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 ...


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 ...


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 ...


Crystal Structure Of The Dna Binding Domain Of The Transcription Factor T-Bet Suggests Simultaneous Recognition Of Distant Genome Sites, Ce Feng Liu, Gabriel S. Brandt, Quyen Q. Hoang, Natalia Naumova, Vanja Lazarevic, Eun Sook Hwang, Job Dekker, Laurie H. Glimcher, Dagmar Ringe, Gregory A. Petsko 2016 Weill Cornell Medical College

Crystal Structure Of The Dna Binding Domain Of The Transcription Factor T-Bet Suggests Simultaneous Recognition Of Distant Genome Sites, Ce Feng Liu, Gabriel S. Brandt, Quyen Q. Hoang, Natalia Naumova, Vanja Lazarevic, Eun Sook Hwang, Job Dekker, Laurie H. Glimcher, Dagmar Ringe, Gregory A. Petsko

Program in Systems Biology Publications and Presentations

The transcription factor T-bet (Tbox protein expressed in T cells) is one of the master regulators of both the innate and adaptive immune responses. It plays a central role in T-cell lineage commitment, where it controls the TH1 response, and in gene regulation in plasma B-cells and dendritic cells. T-bet is a member of the Tbox family of transcription factors; however, T-bet coordinately regulates the expression of many more genes than other Tbox proteins. A central unresolved question is how T-bet is able to simultaneously recognize distant Tbox binding sites, which may be located thousands of base pairs away. We ...


Single-Cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes And Interaction Networks Involved In The Central Circadian Clock, James Park, Haisun Zhu, Sean O'Sullivan, Babatunde A. Ogunnaike, David R. Weaver, James S. Schwaber, Rajanikanth Vadigepalli 2016 Thomas Jefferson University

Single-Cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes And Interaction Networks Involved In The Central Circadian Clock, James Park, Haisun Zhu, Sean O'Sullivan, Babatunde A. Ogunnaike, David R. Weaver, James S. Schwaber, Rajanikanth Vadigepalli

Neurobiology Publications and Presentations

Single-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN). Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular ...


A Gene-Centered C. Elegans Protein-Dna Interaction Network Provides A Framework For Functional Predictions, Juan Fuxman Bass, Carles Pons, Lucie Kozlowski, John S. Reece-Hoyes, Shaleen Shrestha, Amy D. Holdorf, Akihiro Mori, Chad L. Myers, Albertha J. M. Walhout 2016 University of Massachusetts Medical School

A Gene-Centered C. Elegans Protein-Dna Interaction Network Provides A Framework For Functional Predictions, Juan Fuxman Bass, Carles Pons, Lucie Kozlowski, John S. Reece-Hoyes, Shaleen Shrestha, Amy D. Holdorf, Akihiro Mori, Chad L. Myers, Albertha J. M. Walhout

Open Access Articles

Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences. Here, we delineated the largest gene-centered metazoan PDI network to date by examining interactions between 90 ...


Zombies, Predatory Wasps And Consciousness, James K. Peterson 2016 Clemson University

Zombies, Predatory Wasps And Consciousness, James K. Peterson

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Teaching Systems Biology Of The Circadian Clock With Journal Articles And Matlab, Stephanie R. Taylor 2016 Colby College

Teaching Systems Biology Of The Circadian Clock With Journal Articles And Matlab, Stephanie R. Taylor

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Harpy Eagle (Harpia Harpyja) Conservation: Juvenile Behavior And Diet At A Nest Near Pijibasal, Darien, Hannah Rodgers 2016 SIT Study Abroad

Harpy Eagle (Harpia Harpyja) Conservation: Juvenile Behavior And Diet At A Nest Near Pijibasal, Darien, Hannah Rodgers

Independent Study Project (ISP) Collection

The Harpy Eagle (Harpia harpyja), the largest and most powerful bird of prey in the Americas, is declining throughout its range in Neotropical forests. Hunting and deforestation threaten populations in the most important remaining eagle habitat in Central America, the Darien province of Panama. These eagles may have the longest postfledging juvenile dependency of any raptor, though juvenile behavior during this period is poorly studied. This study monitored an 11-month-old juvenile for 7 days at a nest near the indigenous community of Pijibasal in order to study behavior and diet. Researchers recorded the juvenile’s location and behavior, studied prey ...


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