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Disruption Of Synchronous Behavior In Pancreatic Islets Via Hub Cells, Janita Patwardhan 2018 University of Maryland - Baltimore County

Disruption Of Synchronous Behavior In Pancreatic Islets Via Hub Cells, Janita Patwardhan

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 ...


Design And Development Of A Quartz Crystal Microbalance Immunosensor For Exosomes, Wesley Cox 2018 University of Tennessee, Knoxville

Design And Development Of A Quartz Crystal Microbalance Immunosensor For Exosomes, Wesley Cox

University of Tennessee Honors Thesis Projects

No abstract provided.


Determining The Effects Of Quercetin On Cadmium Toxicity In Kidney Cells, Elizabeth Dugan 2018 Bellarmine University

Determining The Effects Of Quercetin On Cadmium Toxicity In Kidney Cells, Elizabeth Dugan

Undergraduate Theses

Cadmium is a heavy transition metal that causes kidney disease via prolonged, low-level exposure due to circulating metallothioneins. These proteins transport cadmium ions to the proximal convoluted tubule, where they induce the creation of reactive oxygen species (ROS). Oxidative damage from ROS can lead to kidney dysfunction and eventually failure. Previous studies have shown that antioxidants, including quercetin, which is found in most fruits and vegetables, can lessen cadmium-induced toxicity. In this study, human embryonic kidney cells were pretreated for one hour with varying concentrations of quercetin ranging from 10 - 100 μM. This was followed by 24-hour treatment with 30 ...


Effects Of Larval Density On Gene Regulation In Caenorhabditis Elegans During Routine L1 Synchronization, Io Long Chan, Oliver J. Rando, Colin C. Conine 2018 University of Massachusetts Medical School

Effects Of Larval Density On Gene Regulation In Caenorhabditis Elegans During Routine L1 Synchronization, Io Long Chan, Oliver J. Rando, Colin C. Conine

University of Massachusetts Medical School Faculty Publications

Bleaching gravid C. elegans followed by a short period of starvation of the L1 larvae is a routine method performed by worm researchers for generating synchronous populations for experiments. During the process of investigating dietary effects on gene regulation in L1 stage worms by single-worm RNA-Seq, we found that the density of resuspended L1 larvae affects expression of many mRNAs. Specifically, a number of genes related to metabolism and signalling are highly expressed in worms arrested at low density, but are repressed at higher arrest densities. We generated a GFP reporter strain based on one of the most density-dependent genes ...


Multiple Molecular Mechanisms Rescue Mtdna Disease In C. Elegans, Suraiya Haroon, Annie Li, Jaye L. Weinert, Clark Fritsch, Nolan G. Ericson, Jasmine Alexander-Floyd, Bart P. Braeckman, Cole M. Haynes, Jason H. Bielas, Tali Gidalevitz, Marc Vermulst 2018 The Children's Hospital of Philadelphia

Multiple Molecular Mechanisms Rescue Mtdna Disease In C. Elegans, Suraiya Haroon, Annie Li, Jaye L. Weinert, Clark Fritsch, Nolan G. Ericson, Jasmine Alexander-Floyd, Bart P. Braeckman, Cole M. Haynes, Jason H. Bielas, Tali Gidalevitz, Marc Vermulst

University of Massachusetts Medical School Faculty Publications

Genetic instability of the mitochondrial genome (mtDNA) plays an important role in human aging and disease. Thus far, it has proven difficult to develop successful treatment strategies for diseases that are caused by mtDNA instability. To address this issue, we developed a model of mtDNA disease in the nematode C. elegans, an animal model that can rapidly be screened for genes and biological pathways that reduce mitochondrial pathology. These worms recapitulate all the major hallmarks of mtDNA disease in humans, including increased mtDNA instability, loss of respiration, reduced neuromuscular function, and a shortened lifespan. We found that these phenotypes could ...


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 ...


The Cjun Nh2-Terminal Kinase (Jnk) Pathway Contributes To Mouse Mammary Gland Remodeling During Involution, Nomeda A. Girnius, Yvonne J. K. Edwards, Roger J. Davis 2018 University of Massachusetts Medical School

The Cjun Nh2-Terminal Kinase (Jnk) Pathway Contributes To Mouse Mammary Gland Remodeling During Involution, Nomeda A. Girnius, Yvonne J. K. Edwards, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

Involution returns the lactating mammary gland to a quiescent state after weaning. The mechanism of involution involves collapse of the mammary epithelial cell compartment. To test whether the cJUN NH2-terminal kinase (JNK) signal transduction pathway contributes to involution, we established mice with JNK deficiency in the mammary epithelium. We found that JNK is required for efficient involution. JNK deficiency did not alter the STAT3/5 or SMAD2/3 signaling pathways that have been previously implicated in this process. Nevertheless, JNK promotes the expression of genes that drive involution, including matrix metalloproteases, cathepsins, and BH3-only proteins. These data demonstrate that JNK ...


Distinct Adipocyte Progenitor Cells Are Associated With Regional Phenotypes Of Perivascular Aortic Fat In Mice, Khanh-Van T. Tran, Timothy P. Fitzgibbons, So Yun Min, Tiffany DeSouza, Silvia Corvera 2018 University of Massachusetts Medical School

Distinct Adipocyte Progenitor Cells Are Associated With Regional Phenotypes Of Perivascular Aortic Fat In Mice, Khanh-Van T. Tran, Timothy P. Fitzgibbons, So Yun Min, Tiffany Desouza, Silvia Corvera

University of Massachusetts Medical School Faculty Publications

OBJECTIVE: Perivascular adipose tissue depots around the aorta are regionally distinct and have specific functional properties. Thoracic aorta perivascular adipose tissue (tPVAT) expresses higher levels of thermogenic genes and lower levels of inflammatory genes than abdominal aorta perivascular adipose tissue (aPVAT). It is not known whether this distinction is due to the in-vivo functional environment or to cell-autonomous traits that persist outside the in-vivo setting. In this study, we asked whether the progenitor cells in tPVAT and aPVAT have cell-autonomous traits that lead to formation of regionally distinct PVAT.

METHODS: We performed microarray analysis of thoracic and abdominal peri-aortic adipose ...


Upr(Mt) Regulation And Output: A Stress Response Mediated By Mitochondrial-Nuclear Communication, Andrew Melber, Cole M. Haynes 2018 University of Massachusetts Medical School

Upr(Mt) Regulation And Output: A Stress Response Mediated By Mitochondrial-Nuclear Communication, Andrew Melber, Cole M. Haynes

University of Massachusetts Medical School Faculty Publications

The mitochondrial network is not only required for the production of energy, essential cofactors and amino acids, but also serves as a signaling hub for innate immune and apoptotic pathways. Multiple mechanisms have evolved to identify and combat mitochondrial dysfunction to maintain the health of the organism. One such pathway is the mitochondrial unfolded protein response (UPR(mt)), which is regulated by the mitochondrial import efficiency of the transcription factor ATFS-1 in C. elegans and potentially orthologous transcription factors in mammals (ATF4, ATF5, CHOP). Upon mitochondrial dysfunction, import of ATFS-1 into mitochondria is reduced, allowing it to be trafficked to ...


Skeletal Myosin Binding Protein-C Isoforms Regulate Thin Filament Activity In A Ca(2+)-Dependent Manner, Brian Leei Lin, Amy Li, Ji Young Mun, Michael J. Previs, Samantha Beck. Previs, Stuart G. Campbell, Cristobal G. Dos Remedios, Pieter de P. Tombe, Roger Craig, David M. Warshaw, Sakthivel Sadayappan 2018 Loyola University Chicago

Skeletal Myosin Binding Protein-C Isoforms Regulate Thin Filament Activity In A Ca(2+)-Dependent Manner, Brian Leei Lin, Amy Li, Ji Young Mun, Michael J. Previs, Samantha Beck. Previs, Stuart G. Campbell, Cristobal G. Dos Remedios, Pieter De P. Tombe, Roger Craig, David M. Warshaw, Sakthivel Sadayappan

Radiology Publications and Presentations

Muscle contraction, which is initiated by Ca(2+), results in precise sliding of myosin-based thick and actin-based thin filament contractile proteins. The interactions between myosin and actin are finely tuned by three isoforms of myosin binding protein-C (MyBP-C): slow-skeletal, fast-skeletal, and cardiac (ssMyBP-C, fsMyBP-C and cMyBP-C, respectively), each with distinct N-terminal regulatory regions. The skeletal MyBP-C isoforms are conditionally coexpressed in cardiac muscle, but little is known about their function. Therefore, to characterize the functional differences and regulatory mechanisms among these three isoforms, we expressed recombinant N-terminal fragments and examined their effect on contractile properties in biophysical assays. Addition of ...


Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu 2018 University of Massachusetts Medical School

Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu

GSBS Dissertations and Theses

Proper functioning of endocrine cells is crucial for organismal homeostasis. The underlying mechanisms that fine-tune the amount, and the timing of hormone secretion are not clear. JIP1 / MAPK8IP1 (JNK interacting protein 1) is a scaffold protein that mediates cellular stress response, and is highly expressed in endocrine cells, including insulin secreting b-cells in pancreas islets. However, the role of JIP1 in b-cells is unclear. This study demonstrates that b-cell specific Jip1 ablation results in decreased glucose-induced insulin secretion, without a change in Insulin1 and Insulin2 gene expression. Inhibition of both JIP1-kinesin interaction, and JIP1-JNK interaction by genetic mutations also resulted ...


Diabetes Impairs Wound Healing By Dnmt1-Dependent Dysregulation Of Hematopoietic Stem Cells Differentiation Towards Macrophages, Jinglian Yan, Guodong Tie, Shoying Wang, Amanda A. Tutto, Natale DeMarco, Lyne Khair, Thomas G. Fazzio, Louis M. Messina 2018 University of Massachusetts Medical School

Diabetes Impairs Wound Healing By Dnmt1-Dependent Dysregulation Of Hematopoietic Stem Cells Differentiation Towards Macrophages, Jinglian Yan, Guodong Tie, Shoying Wang, Amanda A. Tutto, Natale Demarco, Lyne Khair, Thomas G. Fazzio, Louis M. Messina

Open Access Articles

People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1, PU.1, and Klf4 ...


Β-Catenin Regulation Of Adult Skeletal Muscle Plasticity, Yuan Wen 2018 University of Kentucky

Β-Catenin Regulation Of Adult Skeletal Muscle Plasticity, Yuan Wen

Theses and Dissertations--Physiology

Adult skeletal muscle is highly plastic and responds readily to environmental stimuli. One of the most commonly utilized methods to study skeletal muscle adaptations is immunofluorescence microscopy. By analyzing images of adult muscle cells, also known as myofibers, one can quantify changes in skeletal muscle structure and function (e.g. hypertrophy and fiber type). Skeletal muscle samples are typically cut in transverse or cross sections, and antibodies against sarcolemmal or basal lamina proteins are used to label the myofiber boundaries.

The quantification of hundreds to thousands of myofibers per sample is accomplished either manually or semi-automatically using generalized pathology software ...


Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott 2018 Augustana College, Rock Island Illinois

Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 (KEGG map number 02010). We predict these genes encode components of a Branched Chain Amino Acid ATP Binding Cassette (ABC) transporter: 1) Mrub_1325 (DNA coordinates 1357399-1358130 on the reverse strand) encodes the ATP binding domain; 2) Mrub_1326 (DNA coordinates 1358127-1359899 on the reverse strand) encodes the ATP-binding domain and permease domain; 3) Mrub_1327 (DNA coordinates 1359899-1360930 on the reverse strand) encodes a permease domain; and 4)Mrub_1328 (DNA coordinates 1711022-1712185 on the reverse strand) encodes the substrate binding domain. This system is not predicted ...


Molecular Characterization Of The Mummichog (Fundulus Heteroclitus) Ovarian Steroidogenic Pathway And Implications For Exogenous Estrogen Effects During Follicular Development, Thiviya Kanagasabesan 2018 Wilfrid Laurier University

Molecular Characterization Of The Mummichog (Fundulus Heteroclitus) Ovarian Steroidogenic Pathway And Implications For Exogenous Estrogen Effects During Follicular Development, Thiviya Kanagasabesan

Theses and Dissertations (Comprehensive)

This study investigated ovarian development in Fundulus heteroclitus (mummichog), through molecular characterization of key mediators in the ovarian steroidogenic pathway; these included ovarian StAR (steroidogenic acute regulatory protein), cytochrome P450 enzymes, estrogen receptors (ERα, ERβ1 and ERβ2), and gonadotropin receptors (FSHr and LHr); additionally, hepatic vitellogenin (VTG1) and ERs, and brain P450 aromatase (P450arom; CYP19b) were studied. Fish were staged into cortical alveolus, vitellogenic, early mature, late mature, and ovulating stages of maturation; blood (plasma), ovary (tissue and isolated ovarian follicles per stage), liver, and brains were collected. Testosterone (T), 17β-estradiol (E2) and maturation inducing steroid (MIS), measured from ...


Confirmation That Mrub_1751 Is Homologous To E. Coli Xylf, Mrub_1752 Is Homologous To E. Coli Xylh, And Mrub_1753 Is Homologous To E. Coli Xylg, Ben Price, Dr. Lori Scott 2018 Augustana College, Rock Island Illinois

Confirmation That Mrub_1751 Is Homologous To E. Coli Xylf, Mrub_1752 Is Homologous To E. Coli Xylh, And Mrub_1753 Is Homologous To E. Coli Xylg, Ben Price, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1751, Mrub_1752 and Mrub_1753 (KEGG map number 02010). We predict these genes encode components of a D-xylose ATP Binding Cassette (ABC) transporter: 1) Mrub_1752 (DNA coordinates 1809004-1810224 on the forward strand) encodes the permease component (aka transmembrane domain), predicted to be an ortholog and 2) Mrub_1753 (DNA coordinates 1810227-1811000 on the forward strand) encodes the ATP-binding domain (aka nucleotide binding domain); and 3) Mrub_1751 (DNA coordinates 1807855-1808892 on the forward strand) encodes the solute binding protein. The ABC-transporter for M. ruber to transport D-xylose is homologous with the transporter ...


The Impact Of Insulin Dysregulation On Protein Metabolism In Horses, Caroline Margot Marcelle Loos 2018 University of Kentucky

The Impact Of Insulin Dysregulation On Protein Metabolism In Horses, Caroline Margot Marcelle Loos

Theses and Dissertations--Animal and Food Sciences

Insulin plays a vital role in whole-body metabolism and provides a major anabolic stimulus for cellular signaling pathways, including those involved in the metabolism of glucose and protein. Consequently, insulin dysregulation (ID) is known to alter molecular signal transduction in insulin-sensitive tissues such as skeletal muscle, thereby disrupting glucose metabolism and compromising protein synthetic capacity. Our first objective was to induce ID in healthy horses by administering dexamethasone (DEX), a potent glucocorticoid, for 21 days. We evaluated the effects on insulin-stimulated muscle protein signaling components involved in the mammalian target of rapamycin (mTOR) pathway. DEX-induced ID reduced insulin-stimulated activation of ...


Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy 2018 Virginia Commonwealth University

Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy

Theses and Dissertations

Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT2A-dependent upregulation of histone deacetylase ...


Thermophilic Adaptation In Prokaryotes Is Constrained By Metabolic Costs Of Proteostasis, Sergey V. Venev, Konstantin B. Zeldovich 2018 University of Massachusetts Medical School

Thermophilic Adaptation In Prokaryotes Is Constrained By Metabolic Costs Of Proteostasis, Sergey V. Venev, Konstantin B. Zeldovich

Open Access Articles

Prokaryotes evolved to thrive in an extremely diverse set of habitats, and their proteomes bear signatures of environmental conditions. Although correlations between amino acid usage and environmental temperature are well-documented, understanding of the mechanisms of thermal adaptation remains incomplete. Here, we couple the energetic costs of protein folding and protein homeostasis to build a microscopic model explaining both the overall amino acid composition and its temperature trends. Low biosynthesis costs lead to low diversity of physical interactions between amino acid residues, which in turn makes proteins less stable and drives up chaperone activity to maintain appropriate levels of folded, functional ...


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