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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 ...


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 ...


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.


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 ...


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 ...


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 ...


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.


Identification Of Pathway-Specific Serum Biomarkers Of Response To Glucocorticoid And Infliximab Treatment In Children With Inflammatory Bowel Disease, Christopher R. Heier, Alyson A. Fiorillo, Ellen Chaisson, Heather A. Gordish-Dressman, Yetrib Hathout, Jesse M. Damsker, Eric P. Hoffman, Laurie S. Conklin 2016 George Washington University

Identification Of Pathway-Specific Serum Biomarkers Of Response To Glucocorticoid And Infliximab Treatment In Children With Inflammatory Bowel Disease, Christopher R. Heier, Alyson A. Fiorillo, Ellen Chaisson, Heather A. Gordish-Dressman, Yetrib Hathout, Jesse M. Damsker, Eric P. Hoffman, Laurie S. Conklin

Integrative Systems Biology Faculty Publications

Objective:

Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial.

Methods:

We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7). Over 1,100 serum proteins were assayed using aptamer-based SOMAscan proteomics, and 22 miRNAs ...


Prospective Doctoral Statement For The University Of Southern California's School Of Cinematic Arts Media Arts + Practice Program, Gabriel Leiner 2016 University of Southern California

Prospective Doctoral Statement For The University Of Southern California's School Of Cinematic Arts Media Arts + Practice Program, Gabriel Leiner

Gabriel Leiner

After visiting L.A. again and seeing the beautiful fountains on the University of Southern California's campus I am filled with all kinds of ideas about the future and brimming with energy. To all those at the University of Southern California's Cinematic Arts Department, thanks for reading my ideas over the past couple years and helping me to evolve and become a better person and a better writer. Starting a position as a doctoral student in the Media Arts + Practice Program in 2016 is an exciting opportunity. I've got a really positive outlook about Kiss The Water.


Global Intron Retention Mediated Gene Regulation During Cd4+ T Cell Activation., Ting Ni, Wenjing Yang, Miao Han, Yubo Zhang, Ting Shen, Hongbo Nie, Zhihui Zhou, Yalei Dai, Yanqin Yang, Poching Liu, Kairong Cui, Zhouhao Zeng, Yi Tian, Bin Zhou, Gang Wei, Keji Zhao, Weiqun Peng, Jun Zhu 2016 George Washington University

Global Intron Retention Mediated Gene Regulation During Cd4+ T Cell Activation., Ting Ni, Wenjing Yang, Miao Han, Yubo Zhang, Ting Shen, Hongbo Nie, Zhihui Zhou, Yalei Dai, Yanqin Yang, Poching Liu, Kairong Cui, Zhouhao Zeng, Yi Tian, Bin Zhou, Gang Wei, Keji Zhao, Weiqun Peng, Jun Zhu

Integrative Systems Biology Faculty Publications

T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Using strand-specific RNA-seq, we observed that intron retention is prevalent in polyadenylated transcripts in resting CD4(+) T cells and is significantly reduced upon T cell activation. Several lines of evidence suggest that intron-retained transcripts are less stable than fully spliced transcripts. Strikingly, the decrease in intron retention (IR) levels correlate with the increase in steady-state mRNA levels. Further, the majority of the genes upregulated in activated T cells are accompanied by a significant reduction in IR. Of these 1583 genes, 185 genes are predominantly regulated at ...


Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems, Alexander Garza, Megan Eberle, Eric A. Eager 2016 University of Wisconsin-La Crosse

Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems, Alexander Garza, Megan Eberle, Eric A. Eager

Spora: A Journal of Biomathematics

The development of an embryo from a fertilised egg to a multicellular organism proceeds through numerous steps, with the formation of the three germ layers (endoderm, mesoderm, ectoderm) being one of the first. In this paper we study the mesendoderm (the tissue that collectively gives rise to both mesoderm and endoderm) gene regulatory network for two species, \textit{Xenopus laevis} and the axolotl (\textit{Ambystoma mexicanum}) using Boolean networks. We find that previously-established bistability found in these networks can be reproduced using this Boolean framework, provided that some assumptions used in previously-published differential equations models are relaxed. We conclude by ...


Comparison Of Soil Phosphorus Concentration In Farm Restored And Reference Wetlands In Lake County, Il, Catherine L. Pease 2016 CPEASE

Comparison Of Soil Phosphorus Concentration In Farm Restored And Reference Wetlands In Lake County, Il, Catherine L. Pease

DePaul Discoveries

The soil in the Midwest is fertile for agriculture use and therefore a lot of the wetlands have been turned into farmland. Wetlands can act as a sink for excess nutrients such as phosphorus. In part due to their value for nutrient storage, restoration of wetlands has become more frequent, including restoration of wetlands on former farmland. I am interested in phosphorus and the potential of wetlands to either store or release phosphorus. I compared differences in soil reactive phosphorus of restored and reference wetlands. This study compares Prairie Wolf Slough (PWS), a restored wetland, to two reference wetlands, both ...


Metabolic Network Rewiring Of Propionate Flux Compensates Vitamin B12 Deficiency In C. Elegans, Emma Watson, Viridiana Olin-Sandoval, Michael J. Hoy, Chi-Hua Li, Timo Louisse, Victoria Yao, Akihiro Mori, Amy D. Holdorf, Olga G. Troyanskaya, Markus Ralser, Albertha J. M. Walhout 2016 University of Massachusetts Medical School Worcester

Metabolic Network Rewiring Of Propionate Flux Compensates Vitamin B12 Deficiency In C. Elegans, Emma Watson, Viridiana Olin-Sandoval, Michael J. Hoy, Chi-Hua Li, Timo Louisse, Victoria Yao, Akihiro Mori, Amy D. Holdorf, Olga G. Troyanskaya, Markus Ralser, Albertha J. M. Walhout

Open Access Articles

Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked ...


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 2016 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

Ecology, Evolution and Organismal Biology Publications

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 ...


Evolutionary Ecology Of Weeds, 1st & 2nd Editions, Jack Dekker 2016 Retired: Iowa State University-University of Guelph-Michigan State University

Evolutionary Ecology Of Weeds, 1st & 2nd Editions, Jack Dekker

Jack Dekker

2nd Edition, July 2016.  Evolutionary Ecology of Weeds is the story of WHAT, WHY and HOW some plant species invade and occupy habitats ripe for exploitation.  The nature of weeds is the evolution of adaptive traits for seizing and exploiting locally available opportunity.  Weeds are the consequence of human disturbance which creates opportunity spacetime, leaving unused resources eager for invasion by weeds.  The nature of weeds is the story of us, humans.  We created highly successful wild-crop-weed complexes that resist control.  We created them by channeling natural selection, the driver of biological change.  Plants invade by dispersing, colonizing, reproducing and ...


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