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Sources And Fates Of Carbamyl Phosphate: A Labile Energy-Rich Molecule With Multiple Facets., Dashuang Shi, Ljubica Caldovic, Mendel Tuchman 2018 George Washington University

Sources And Fates Of Carbamyl Phosphate: A Labile Energy-Rich Molecule With Multiple Facets., Dashuang Shi, Ljubica Caldovic, Mendel Tuchman

Genomics and Precision Medicine Faculty Publications

Carbamyl phosphate (CP) is well-known as an essential intermediate of pyrimidine and arginine/urea biosynthesis. Chemically, CP can be easily synthesized from dihydrogen phosphate and cyanate. Enzymatically, CP can be synthesized using three different classes of enzymes: (1) ATP-grasp fold protein based carbamyl phosphate synthetase (CPS); (2) Amino-acid kinase fold carbamate kinase (CK)-like CPS (anabolic CK or aCK); and (3) Catabolic transcarbamylase. The first class of CPS can be further divided into three different types of CPS as CPS I, CPS II, and CPS III depending on the usage of ammonium or glutamine as its nitrogen source, and whether


Obat Aborsi Penajam 081901222272 Jual Obat Cytotec Asli Di Penajam, Apotik Cytotec 2018 Bryant University

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Generation Of Nonlinear-Differential-Equations System From A Model Of Boolean Relationships In Arabidopsis Salt Stress Network, Renee Dale 2018 Louisiana State University and Agricultural and Mechanical College

Generation Of Nonlinear-Differential-Equations System From A Model Of Boolean Relationships In Arabidopsis Salt Stress Network, Renee Dale

Biology and Medicine Through Mathematics Conference

No abstract provided.


Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender 2018 Fordham University

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim ...


Studying Planarian Regeneration Aboard The International Space Station Within The Student Space Flight Experimental Program, Vista SSEP Mission 11 Team, D. Hagstrom, C. Bartee, Eva-Maria S. Collins 2018 Swarthmore College

Studying Planarian Regeneration Aboard The International Space Station Within The Student Space Flight Experimental Program, Vista Ssep Mission 11 Team, D. Hagstrom, C. Bartee, Eva-Maria S. Collins

Biology Faculty Works

The growing possibilities of space travel are quickly moving from science fiction to reality. However, to realize the dream of long-term space travel, we must understand how these conditions affect biological and physiological processes. Planarians are master regenerators, famous for their ability to regenerate from very small parts of the original animal. Understanding how this self-repair works may inspire regenerative therapies in humans. Two studies conducted aboard the International Space Station (ISS) showed that planarian regeneration is possible in microgravity. One study reported no regenerative defects, whereas the other study reported behavioral and microbiome alterations post-space travel and found that ...


Modeling And Analyzing An Optogenetic System For Photoactivatable Protein Dissociation, Anvin Thomas, James Schaff 2018 University of Connecticut

Modeling And Analyzing An Optogenetic System For Photoactivatable Protein Dissociation, Anvin Thomas, James Schaff

Honors Scholar Theses

Computational modeling of cell-cell interactions can grant clues and can answer questions about an experiment, especially for observations about binding interactions and kinetics. This approach was used to investigate an interaction between a light-oxygen-voltage (LOV) domain and an engineered protein called Zdark (Zdk). The LOV domain is membrane-bound while Zdk is cytosolic. The LOV domain and Zdk bind strongly in dark (Kd 26.2 nM), and weakly upon exposure to blue light (Kd > 4 μM). Total internal reflection fluorescence (TIRF) images are acquired of Zdk, the fluorescent species bound to a mCherry tag, and the loss of fluorescence ...


Exploiting Glycan Topography For Computational Design Of Env Glycoprotein Antigenicity, Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, Galit Alter 2018 Massachusetts Institute of Technology

Exploiting Glycan Topography For Computational Design Of Env Glycoprotein Antigenicity, Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, Galit Alter

Open Access Articles

Mounting evidence suggests that glycans, rather than merely serving as a "shield", contribute critically to antigenicity of the HIV envelope (Env) glycoprotein, representing critical antigenic determinants for many broadly neutralizing antibodies (bNAbs). While many studies have focused on defining the role of individual glycans or groups of proximal glycans in bNAb binding, little is known about the effects of changes in the overall glycan landscape in modulating antibody access and Env antigenicity. Here we developed a systems glycobiology approach to reverse engineer the complexity of HIV glycan heterogeneity to guide antigenicity-based de novo glycoprotein design. bNAb binding was assessed against ...


Skeletal, Cardiac, And Respiratory Muscle Function And Histopathology In The P448lneo- Mouse Model Of Fkrp-Deficient Muscular Dystrophy., Qing Yu, Melissa Morales, Ning Li, Alexander G Fritz, Ren Ruobing, Anthony Blaeser, Ershia Francois, Qi-Long Lu, Kanneboyina Nagaraju, Christopher F Spurney 2018 George Washington University

Skeletal, Cardiac, And Respiratory Muscle Function And Histopathology In The P448lneo- Mouse Model Of Fkrp-Deficient Muscular Dystrophy., Qing Yu, Melissa Morales, Ning Li, Alexander G Fritz, Ren Ruobing, Anthony Blaeser, Ershia Francois, Qi-Long Lu, Kanneboyina Nagaraju, Christopher F Spurney

Genomics and Precision Medicine Faculty Publications

BACKGROUND: Fukutin-related protein (FKRP) mutations are the most common cause of dystroglycanopathies known to cause both limb girdle and congenital muscular dystrophy. The P448Lneo- mouse model has a knock-in mutation in the FKRP gene and develops skeletal, respiratory, and cardiac muscle disease.

METHODS: We studied the natural history of the P448Lneo- mouse model over 9 months and the effects of twice weekly treadmill running. Forelimb and hindlimb grip strength (Columbus Instruments) and overall activity (Omnitech Electronics) assessed skeletal muscle function. Echocardiography was performed using VisualSonics Vevo 770 (FujiFilm VisualSonics). Plethysmography was performed using whole body system (ADInstruments). Histological evaluations included ...


C. Elegans Mrp-5 Exports Vitamin B12 From Mother To Offspring To Support Embryonic Development, Huimin Na, Olga Ponomarova, Gabrielle E. Giese, Albertha J. M. Walhout 2018 University of Massachusetts Medical School

C. Elegans Mrp-5 Exports Vitamin B12 From Mother To Offspring To Support Embryonic Development, Huimin Na, Olga Ponomarova, Gabrielle E. Giese, Albertha J. M. Walhout

Program in Systems Biology Publications and Presentations

Vitamin B12 functions as a cofactor for methionine synthase to produce the anabolic methyl donor S-adenosylmethionine (SAM) and for methylmalonyl-CoA mutase to catabolize the short-chain fatty acid propionate. In the nematode Caenorhabditis elegans, maternally supplied vitamin B12 is required for the development of offspring. However, the mechanism for exporting vitamin B12 from the mother to the offspring is not yet known. Here, we use RNAi of more than 200 transporters with a vitamin B12-sensor transgene to identify the ABC transporter MRP-5 as a candidate vitamin B12 exporter. We show that the injection of vitamin B12 into the gonad of mrp-5 ...


Dynamic Modeling And Stochastic Simulation Of Metabolic Networks, Emalie Clement 2018 University of Nebraska at Omaha

Dynamic Modeling And Stochastic Simulation Of Metabolic Networks, Emalie Clement

Student Research and Creative Activity Fair

Throughout our current generation, scientific studies, with the help of increased technological methods, have enabled the investigation of biology at nanoscale levels. Nevertheless, such systems necessitate the use of computational methods to comprehend the complex interactions occurring. Traditionally, dynamics of metabolic systems are described by ordinary differential equations producing a deterministic result which negates the intrinsic heterogeneity of intracellular systems. More recently, stochastic modeling approaches have gained popularity with the capability of providing more realistic outcomes. Yet, solving stochastic algorithms tend to be computationally intensive processes. Employing the queueing theory, an approach commonly used to evaluate telecommunication networks, reduces the ...


Herbivory And Drought Generate Short‐Term Stochasticity And Long‐Term Stability In A Savanna Understory Community, Corinna Riginos, Lauren M. Porensky, Kari E. Veblen, Truman P. Young 2018 University of Wyoming

Herbivory And Drought Generate Short‐Term Stochasticity And Long‐Term Stability In A Savanna Understory Community, Corinna Riginos, Lauren M. Porensky, Kari E. Veblen, Truman P. Young

Wildland Resources Faculty Publications

Rainfall and herbivory are fundamental drivers of grassland plant dynamics, yet few studies have examined long‐term interactions between these factors in an experimental setting. Understanding such interactions is important, as rainfall is becoming increasingly erratic and native wild herbivores are being replaced by livestock. Livestock grazing and episodic low rainfall are thought to interact, leading to greater community change than either factor alone. We examined patterns of change and stability in herbaceous community composition through four dry periods, or droughts, over 15 years of the Kenya Long‐term Exclosure Experiment (KLEE), which consists of six different combinations of cattle ...


Emergence Of The Erythroid Lineage From Multipotent Hematopoiesis, Betsabeh K. Tusi, Samuel L. Wolock, Caleb Weinreb, Yung Hwang, Daniel Hidalgo, Rapolas Zilionis, Ari Waisman, Jun R. Huh, Allon M. Klein, Merav Socolovsky 2018 University of Massachusetts Medical School

Emergence Of The Erythroid Lineage From Multipotent Hematopoiesis, Betsabeh K. Tusi, Samuel L. Wolock, Caleb Weinreb, Yung Hwang, Daniel Hidalgo, Rapolas Zilionis, Ari Waisman, Jun R. Huh, Allon M. Klein, Merav Socolovsky

University of Massachusetts Medical School Faculty Publications

Red cell formation begins with the hematopoietic stem cell, but the manner by which it gives rise to erythroid progenitors, and their subsequent developmental path, remain unclear. Here we combined single-cell transcriptomics of murine hematopoietic tissues with fate potential assays to infer a continuous yet hierarchical structure for the hematopoietic network. We define the erythroid differentiation trajectory as it emerges from multipotency and diverges from 6 other blood lineages. With the aid of a new flow-cytometric sorting strategy, we validated predicted cell fate potentials at the single cell level, revealing a coupling between erythroid and basophil/mast cell fates. We ...


Systems Modeling Accurately Predicts Responses To Genotoxic Agents And Their Synergism With Bcl-2 Inhibitors In Triple Negative Breast Cancer Cells., Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen HM Prehn 2018 Royal College of Surgeons in Ireland

Systems Modeling Accurately Predicts Responses To Genotoxic Agents And Their Synergism With Bcl-2 Inhibitors In Triple Negative Breast Cancer Cells., Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen Hm Prehn

Physiology and Medical Physics Articles

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis. Here we determined whether DR_MOMP predicts responses of TNBC cells to genotoxic agents and the re-sensitization of resistant cells ...


The Mayfly Newsletter, Donna J. Giberson 2018 The Permanent Committee of the International Conferences on Ephemeroptera

The Mayfly Newsletter, Donna J. Giberson

The Mayfly Newsletter

No abstract provided.


Rest Upregulates Gremlin To Modulate Diffuse Intrinsic Pontine Glioma Vasculature, Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Javad Nazarian, +several additional authors 2018 George Washington University

Rest Upregulates Gremlin To Modulate Diffuse Intrinsic Pontine Glioma Vasculature, Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Javad Nazarian, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive glial tumor that occurs in children. The extremely poor median and 5-year survival in children afflicted with DIPG highlights the need for novel biology-driven therapeutics. Here, we have implicated the chromatin remodeler and regulator of brain development called RE1 Silencing Transcription Factor (REST), in DIPG pathology. We show that REST protein is aberrantly elevated in at least 21% of DIPG tumors compared to normal controls. Its knockdown in DIPG cell lines diminished cell growth and decreased their tumorigenicity in mouse intracranial models. DIPGs are vascularized tumors and interestingly, REST loss in ...


Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., James A. Ratti 2018 Virginia Commonwealth University

Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., James A. Ratti

Theses and Dissertations

COPD is characterized by tissue inflammation and impaired remodeling that suggests fibroblast maintenance of structural homeostasis is dysregulated. Thus, we performed in vitro wound healing experiments on normal and diseased human lung fibroblasts and developed an ABM of fibroblasts closing a scratched monolayer using NetLogo to evaluate differences due to COPD or cigarette smoke condensate exposure. This ABM consists of a rule-set governing the healing response, accounting for cell migration, proliferation, death, activation and senescence rates; along with the effects of heterogeneous activation, phenotypic changes, serum deprivation and exposure to cigarette smoke condensate or bFGF. Simulations were performed to calibrate ...


Molecular And Functional Analysis Of Anchorage Independent, Treatment-Evasive Neuroblastoma Tumorspheres With Enhanced Malignant Properties: A Possible Explanation For Radio-Therapy Resistance, Tamara Abou-Antoun, Javad Nazarian, Anthony Ghanem, Stanislav Vukmanovic, Anthony D. Sandler 2018 George Washington University

Molecular And Functional Analysis Of Anchorage Independent, Treatment-Evasive Neuroblastoma Tumorspheres With Enhanced Malignant Properties: A Possible Explanation For Radio-Therapy Resistance, Tamara Abou-Antoun, Javad Nazarian, Anthony Ghanem, Stanislav Vukmanovic, Anthony D. Sandler

Genomics and Precision Medicine Faculty Publications

Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures. To expand our molecular characterization of the AI tumorspheres, we sought to define the comprehensive proteomic profile of murine AD and AI neuroblastoma cells. The proteomic ...


Mass Action Modeling Of Catalysis Through Reaction Flux Estimation, Ethan Stancliffe 2018 University of Iowa

Mass Action Modeling Of Catalysis Through Reaction Flux Estimation, Ethan Stancliffe

University of Iowa Honors Theses

The complexity of biochemical networks necessitates the use of computational and mathematical frameworks to accurately characterize and study these systems. However, modern frameworks developed for this task have inadequacies that limit their accuracy or scalability. In this report, a mathematical model of the canonical enzyme substrate binding network is developed, and, using estimated true and maximal reaction rates, a methodology utilizing principles of flux balance analysis is developed to deduce the individual reaction rate constants in the network. It is then shown that these two reaction rates are not sufficient to unambiguously define a mass action kinetic model of this ...


Taming The Beast—A Community Teaching Material Resource For Beast 2, Joelle Barido-Sottani, Veronika Boskova, Louis du Plessis, Denise Kuhnert, Carsten Magnus, Venelin Mitov, Nicola F. Muller, Julia Pecerska, David A. Rasmussen, Chi Zhang, Alexei J. Drummond, Tracy A. Heath, Oliver G. Pybus, Timothy G. Vaughan, Tanja Stadler 2018 ETH Zurich

Taming The Beast—A Community Teaching Material Resource For Beast 2, Joelle Barido-Sottani, Veronika Boskova, Louis Du Plessis, Denise Kuhnert, Carsten Magnus, Venelin Mitov, Nicola F. Muller, Julia Pecerska, David A. Rasmussen, Chi Zhang, Alexei J. Drummond, Tracy A. Heath, Oliver G. Pybus, Timothy G. Vaughan, Tanja Stadler

Ecology, Evolution and Organismal Biology Publications

Phylogenetics and phylodynamics are central topics in modern evolutionary biology. Phylogenetic methods reconstruct the evolutionary relationships among organisms, whereas phylodynamic approaches reveal the underlying diversification processes that lead to the observed relationships. These two fields have many practical applications in disciplines as diverse as epidemiology, developmental biology, palaeontology, ecology, and linguistics. The combination of increasingly large genetic data sets and increases in computing power is facilitating the development of more sophisticated phylogenetic and phylodynamic methods. Big data sets allow us to answer complex questions. However, since the required analyses are highly specific to the particular data set and question, a ...


Hepatic Dysfunction Caused By Consumption Of A High-Fat Diet, Anthony R. Soltis, Norman J. Kennedy, Xiaofeng Xin, Feng Zhou, Scott B. Ficarro, Yoon Sing Yap, Bryan J. Matthews, Douglas A. Lauffenburger, Forest M. White, Jarrod A. Marto, Roger J. Davis, Ernest Fraenkel 2017 Massachusetts Institute of Technology

Hepatic Dysfunction Caused By Consumption Of A High-Fat Diet, Anthony R. Soltis, Norman J. Kennedy, Xiaofeng Xin, Feng Zhou, Scott B. Ficarro, Yoon Sing Yap, Bryan J. Matthews, Douglas A. Lauffenburger, Forest M. White, Jarrod A. Marto, Roger J. Davis, Ernest Fraenkel

University of Massachusetts Medical School Faculty Publications

Obesity is a major human health crisis that promotes insulin resistance and, ultimately, type 2 diabetes. The molecular mechanisms that mediate this response occur across many highly complex biological regulatory levels that are incompletely understood. Here, we present a comprehensive molecular systems biology study of hepatic responses to high-fat feeding in mice. We interrogated diet-induced epigenomic, transcriptomic, proteomic, and metabolomic alterations using high-throughput omic methods and used a network modeling approach to integrate these diverse molecular signals. Our model indicated that disruption of hepatic architecture and enhanced hepatocyte apoptosis are among the numerous biological processes that contribute to early liver ...


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