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Bioaccumulation Of Metallic Trace Elements And Antioxidant Enzyme Activities In Apfelbeckia Insculpta (L. Koch, 1867) (Diplopoda: Callipodida) From The Cave Hadži-Prodanova Pećina (Serbia), Jelena Vranković, Slavica Borković-Mitić, Bojan Ilić, Milanka Radulović, Slaviša Milošević, Slobodan Makarov, Bojan Mitić 2017 University of Belgrade

Bioaccumulation Of Metallic Trace Elements And Antioxidant Enzyme Activities In Apfelbeckia Insculpta (L. Koch, 1867) (Diplopoda: Callipodida) From The Cave Hadži-Prodanova Pećina (Serbia), Jelena Vranković, Slavica Borković-Mitić, Bojan Ilić, Milanka Radulović, Slaviša Milošević, Slobodan Makarov, Bojan Mitić

International Journal of Speleology

The concentration of 10 metallic trace elements or MTE (Cu, Fe, Zn, Mn, As, Hg, Pb, Cd, Ni, and Cr) was measured in specimens of the troglophilic millipede Apfelbeckia insculpta (L. Koch, 1867) and sediment of the cave Hadži-Prodanova Pećina in western Serbia. Some MTE, like Fe and Mn, displayed much higher concentrations compared to other elements, both in the sediment and in the body of A. insculpta. On the other hand, estimation of the bioaccumulation factor (BAF) in both males and females of A. insculpta showed values greater than 1 for xenobiotic elements compared to those that are essential ...


Increased Mitochondrial Superoxide In The Brain, But Not Periphery, Sensitizes Mice To Angiotensin Ii-Mediated Hypertension., Adam J. Case, Jun Tian, Matthew C. Zimmerman 2016 University of Nebraska Medical Center

Increased Mitochondrial Superoxide In The Brain, But Not Periphery, Sensitizes Mice To Angiotensin Ii-Mediated Hypertension., Adam J. Case, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) elicits the production of superoxide (O2(•-)) from mitochondria in numerous cell types within peripheral organs and in the brain suggesting a role for mitochondrial-produced O2(•-) in the pathogenesis of hypertension. However, it remains unclear if mitochondrial O2(•-) is causal in the development of AngII-induced hypertension, or if mitochondrial O2(•-) in the absence of elevated AngII is sufficient to increase blood pressure. Further, the tissue specific (i.e. central versus peripheral) redox regulation of AngII hypertension remains elusive. Herein, we hypothesized that increased mitochondrial O2(•-) in the absence of pro-hypertensive stimuli, such as AngII, elevates baseline systemic mean ...


Altered Interleukin-10 Signaling In Skeletal Muscle Regulates Obesity-Mediated Inflammation And Insulin Resistance, Sezin Dagdeviren, Dae Young Jung, Eunjung Lee, Randall H. Friedline, Hye Lim Noh, Jong Hun. Kim, Payal R. Patel, Nicholas Tsitsilianos, Andrew V. Tsitsilianos, Duy A. Tran, George H. Tsougranis, Caitlyn C. Kearns, Cecilia P. Uong, Jung Yeon. Kwon, Werner Muller, Ki Won. Lee, Jason K. Kim 2016 University of Massachusetts Medical School

Altered Interleukin-10 Signaling In Skeletal Muscle Regulates Obesity-Mediated Inflammation And Insulin Resistance, Sezin Dagdeviren, Dae Young Jung, Eunjung Lee, Randall H. Friedline, Hye Lim Noh, Jong Hun. Kim, Payal R. Patel, Nicholas Tsitsilianos, Andrew V. Tsitsilianos, Duy A. Tran, George H. Tsougranis, Caitlyn C. Kearns, Cecilia P. Uong, Jung Yeon. Kwon, Werner Muller, Ki Won. Lee, Jason K. Kim

University of Massachusetts Medical School Faculty Publications

Skeletal muscle insulin resistance is a major characteristic of obesity and type 2 diabetes. Although obesity-mediated inflammation is causally associated with insulin resistance, the underlying mechanism is unclear. Here, we examined the effects of chronic obesity in mice with muscle-specific overexpression of interleukin-10 (MIL10). After 16 weeks of a high-fat diet (HFD), MIL10 mice became markedly obese but showed improved insulin action compared to that of wild-type mice, which was largely due to increased glucose metabolism and reduced inflammation in skeletal muscle. Since leptin regulates inflammation, the beneficial effects of interleukin-10 (IL-10) were further examined in leptin-deficient ob/ob mice ...


Transient Runx1 Expression During Early Mesendodermal Differentiation Of Hescs Promotes Epithelial To Mesenchymal Transition Through Tgfb2 Signaling, Jennifer J. VanOudenhove, Ricardo F. Medina, Prachi N. Ghule University of Vermont College of Medicine, Jane B. Lian, Janet L. Stein, Sayyed K. Zaidi, Gary S. Stein 2016 University of Massachusetts Medical School

Transient Runx1 Expression During Early Mesendodermal Differentiation Of Hescs Promotes Epithelial To Mesenchymal Transition Through Tgfb2 Signaling, Jennifer J. Vanoudenhove, Ricardo F. Medina, Prachi N. Ghule University Of Vermont College Of Medicine, Jane B. Lian, Janet L. Stein, Sayyed K. Zaidi, Gary S. Stein

Open Access Articles

The transition of human embryonic stem cells (hESCs) from pluripotency to lineage commitment is not fully understood, and a role for phenotypic transcription factors in the initial stages of hESC differentiation remains to be explored. From a screen of candidate factors, we found that RUNX1 is selectively and transiently upregulated early in hESC differentiation to mesendodermal lineages. Transcriptome profiling and functional analyses upon RUNX1 depletion established a role for RUNX1 in promoting cell motility. In parallel, we discovered a loss of repression for several epithelial genes, indicating that loss of RUNX1 impaired an epithelial to mesenchymal transition during differentiation. Cell ...


Chrebp Regulates Fructose-Induced Glucose Production Independently Of Insulin Signaling, Mi-Sung Kim, Sarah A. Krawczyk, Ludivine Doridot, Alan J. Fowler, Jennifer X. Wang, Sunia A. Trauger, Hye Lim Noh, Hee Joon Kang, John K. Meissen, Matthew Blatnik, Jason K. Kim, Michelle Lai, Mark A. Herman 2016 Beth Israel Deaconess Medical Cente

Chrebp Regulates Fructose-Induced Glucose Production Independently Of Insulin Signaling, Mi-Sung Kim, Sarah A. Krawczyk, Ludivine Doridot, Alan J. Fowler, Jennifer X. Wang, Sunia A. Trauger, Hye Lim Noh, Hee Joon Kang, John K. Meissen, Matthew Blatnik, Jason K. Kim, Michelle Lai, Mark A. Herman

University of Massachusetts Medical School Faculty Publications

Obese, insulin-resistant states are characterized by a paradoxical pathogenic condition in which the liver appears to be selectively insulin resistant. Specifically, insulin fails to suppress glucose production, yet successfully stimulates de novo lipogenesis. The mechanisms underlying this dysregulation remain controversial. Here, we hypothesized that carbohydrate-responsive element-binding protein (ChREBP), a transcriptional activator of glycolytic and lipogenic genes, plays a central role in this paradox. Administration of fructose increased hepatic hexose-phosphate levels, activated ChREBP, and caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis in mice. Activation of ChREBP was required for the increased expression of glycolytic and lipogenic genes as well as ...


Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla 2016 The University of Western Ontario

Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla

Electronic Thesis and Dissertation Repository

Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR1 and 5-HT2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT2A/CRs. The first purpose of this ...


Macrophages Are Regulators Of Whole Body Metabolism: A Dissertation, Joseph C. Yawe 2016 University of Massachusetts Medical School

Macrophages Are Regulators Of Whole Body Metabolism: A Dissertation, Joseph C. Yawe

GSBS Dissertations and Theses

Obesity is the top risk factor for the development of type 2 diabetes mellitus in humans. Obese adipose tissue, particularly visceral depots, exhibits an increase in macrophage accumulation and is described as being in a state of chronic low-grade inflammation. It is characterized by the increased expression and secretion of inflammatory cytokines produced by both macrophages and adipocytes, and is associated with the development of insulin resistance. Based on these observations, we investigated the potential role of macrophage infiltration on whole body metabolism, using genetic and diet-induced mouse models of obesity.

Using flow cytometry and immunofluorescence imaging we found that ...


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 ...


Maintenance Of The Ph Gradient In The Gastric Mucus Layer., Owen Lewis 2016 The University Of Utah

Maintenance Of The Ph Gradient In The Gastric Mucus Layer., Owen Lewis

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


The Rna-Binding Protein Atx-2 Regulates Cytokinesis Through Par-5 And Zen-4, Megan M. Gnazzo, Eva-Maria E. Uhlemann, Alex R. Villarreal, Masaki Shirayama, Eddie G. Dominguez, Ahna R. Skop 2016 University of Wisconsin-Madison

The Rna-Binding Protein Atx-2 Regulates Cytokinesis Through Par-5 And Zen-4, Megan M. Gnazzo, Eva-Maria E. Uhlemann, Alex R. Villarreal, Masaki Shirayama, Eddie G. Dominguez, Ahna R. Skop

Open Access Articles

The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5-GFP, and ultimately a reduction of ...


Understanding Adipocyte Dynamics Through Mathematical Modeling, Katrina Johnson, Fred Adler 2016 University of Utah

Understanding Adipocyte Dynamics Through Mathematical Modeling, Katrina Johnson, Fred Adler

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Mitochondrial Superoxide Signaling Contributes To Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles., Adam J. Case, Colton T. Roessner, Jun Tian, Matthew C. Zimmerman 2016 University of Nebraska Medical Center

Mitochondrial Superoxide Signaling Contributes To Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles., Adam J. Case, Colton T. Roessner, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Norepinephrine (NE) produces multifaceted regulatory patterns in T-lymphocytes. Recently, we have shown that NE utilizes redox signaling as evidenced by increased superoxide (O2●-) causally linked to the observed changes in these cells; however, the source of this reactive oxygen species (ROS) remains elusive. Herein, we hypothesized that the source of increased O2●- in NE-stimulated T-lymphocytes is due to disruption of mitochondrial bioenergetics. To address this hypothesis, we utilized purified mouse splenic CD4+ and CD8+ T-lymphocytes stimulated with NE and assessed O2●- levels, mitochondrial metabolism, cellular proliferation, and cytokine profiles. We demonstrate that the increase in O2●- levels in response to ...


Sexual Dimorphism In Alcohol Induced Adipose Inflammation Relates To Liver Injury, Melissa A. Fulham, Pranoti Mandrekar 2016 University of Massachusetts Medical School

Sexual Dimorphism In Alcohol Induced Adipose Inflammation Relates To Liver Injury, Melissa A. Fulham, Pranoti Mandrekar

Open Access Articles

Alcoholic liver disease occurs due to chronic, heavy drinking and is driven both by metabolic alterations and immune cell activation. Women are at a higher risk than men for developing alcohol induced liver injury and this dimorphism is reflected in animal models of alcoholic liver disease. The importance of adipose tissue in alcoholic liver disease is emerging. Chronic alcohol consumption causes adipose tissue inflammation, which can influence liver injury. Sex differences in body fat composition are well known. However, it is still unclear if alcohol-induced adipose tissue inflammation occurs in a sex-dependent manner. Here we have employed the clinically relevant ...


Effects Of S1p Mutation On Er Stress And Cholesterol Synthesis Markers In Human Epithelial Cells, Connie Gan, George G. Schweitzer, Rita T. Brookheart, Robert C. Bucelli, Brian N. Finck 2016 Washington University in St. Louis

Effects Of S1p Mutation On Er Stress And Cholesterol Synthesis Markers In Human Epithelial Cells, Connie Gan, George G. Schweitzer, Rita T. Brookheart, Robert C. Bucelli, Brian N. Finck

Undergraduate Research Symposium Posters

Site-1 Protease (S1P) is a Golgi-resident enzyme required for activation and subsequent nuclear localization of several major transcription factors. A 24-year-old female patient with a de novo single point mutation in S1P presented with a complex phenotype of gut hypomotility, abnormal optic nerves, and polycystic ovarian syndrome. Furthermore, this patient suffers from phenotypes related to skeletal muscle dysfunction, resulting in decreased ability to perform physical exercise due to unusual post-exercise pain, fatigue, nausea, and vomiting. This phenomenon has been described in the literature to manifest from myoedema and the breakdown of muscle that releases intracellular proteins into the blood, or ...


Adipocyte-Specific Hypoxia-Inducible Gene 2 Promotes Fat Deposition And Diet-Induced Insulin Resistance, Marina DiStefano, Rachel J. Roth Flach, Ozlem Senol-Cosar, Laura V. Danai, Joseph V. Virbasius, Sarah M. Nicoloro, Juerg R. Straubhaar, Sezin Dagdeviren, Martin Wabitsch, Olga T. Gupta, Jason K. Kim, Michael P. Czech 2016 University of Massachusetts Medical School

Adipocyte-Specific Hypoxia-Inducible Gene 2 Promotes Fat Deposition And Diet-Induced Insulin Resistance, Marina Distefano, Rachel J. Roth Flach, Ozlem Senol-Cosar, Laura V. Danai, Joseph V. Virbasius, Sarah M. Nicoloro, Juerg R. Straubhaar, Sezin Dagdeviren, Martin Wabitsch, Olga T. Gupta, Jason K. Kim, Michael P. Czech

Open Access Articles

OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis.

METHOD: White and brown adipocyte-deficient (Hig2fl/fl x Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2fl/fl x Ucp1 cre+) mice were generated to investigate the role of Hig2 in ...


An Alternative Splicing Program Promotes Adipose Tissue Thermogenesis, Santiago Vernia, Yvonne J. K. Edwards, Myoung Souk Han, Julie Cavanagh-Kyros, Tamera Barrett, Jason K. Kim, Roger J. Davis 2016 University of Massachusetts Medical School

An Alternative Splicing Program Promotes Adipose Tissue Thermogenesis, Santiago Vernia, Yvonne J. K. Edwards, Myoung Souk Han, Julie Cavanagh-Kyros, Tamera Barrett, Jason K. Kim, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

Alternative pre-mRNA splicing expands the complexity of the transcriptome and controls isoform-specific gene expression. Whether alternative splicing contributes to metabolic regulation is largely unknown. Here we investigated the contribution of alternative splicing to the development of diet-induced obesity. We found that obesity-induced changes in adipocyte gene expression include alternative pre-mRNA splicing. Bioinformatics analysis associated part of this alternative splicing program with sequence specific NOVA splicing factors. This conclusion was confirmed by studies of mice with NOVA deficiency in adipocytes. Phenotypic analysis of the NOVA-deficient mice demonstrated increased adipose tissue thermogenesis and improved glycemia. We show that NOVA proteins mediate a ...


Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad 2016 The University of Western Ontario

Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad

Electronic Thesis and Dissertation Repository

PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the ...


Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis 2016 University of Massachusetts Medical School

Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis

Davis Lab

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive ...


Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee 2016 University of Massachusetts Medical School

Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee

GSBS Dissertations and Theses

Glioblastoma multiforme (GBM) is a deadly grade IV brain tumor characterized by a heterogeneous population of cells that are drug resistant, aggressive, and infiltrative. The current standard of care, which has not changed in over a decade, only provides GBM patients with 12-14 months survival post diagnosis. We asked if the addition of a novel endoplasmic reticulum (ER) stress inducing agent, JLK1486, to the standard chemotherapy, temozolomide (TMZ), which induces DNA double strand breaks (DSBs), would enhance TMZ’s efficacy. Because GBMs rely on the ER to mitigate their hypoxic environment and DNA repair to fix TMZ induced DSBs, we ...


Long-Term Treatment With Insulin And Retinoic Acid Increased Glucose Usage In L6 Muscle Cells Via Glycogenesis, Matthew Ray Goff 2016 University of Tennessee, Knoxville

Long-Term Treatment With Insulin And Retinoic Acid Increased Glucose Usage In L6 Muscle Cells Via Glycogenesis, Matthew Ray Goff

Doctoral Dissertations

Skeletal muscle glucose metabolism can affect whole body glucose homeostasis significantly. Vitamin A (VA) plays a role in a number of physiological functions including glucose metabolism. However, its role in skeletal muscle glucose metabolism has not been well established. Insulin controls glucose metabolism in the skeletal muscle via the regulations of glucose uptake, glycogenesis, and glycolysis. We hypothesize that insulin and VA signaling pathways may converge to regulate glucose metabolism in skeletal muscle. Here, the effects of retinoic acid (RA) alone and in combination with insulin on glucose utilization in rat L6 muscle cells were studied. L6 cells were treated ...


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