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Physiology

2014

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Articles 1 - 30 of 43

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Chromatin Regulators And Dna Repair: A Dissertation, Gwendolyn M. Bennett Dec 2014

Chromatin Regulators And Dna Repair: A Dissertation, Gwendolyn M. Bennett

GSBS Dissertations and Theses

DNA double-strand break (DSB) repair is essential for maintenance of genome stability. However, the compaction of the eukaryotic genome into chromatin creates an inherent barrier to any DNA-mediated event, such as during DNA repair. This demands that there be mechanisms to modify the chromatin structure and thus access DNA. Recent work has implicated a host of chromatin regulators in the DNA damage response and several functional roles have been defined. Yet the mechanisms that control their recruitment to DNA lesions, and their relationship with concurrent histone modifications, remain unclear. We find that efficient DSB recruitment of many yeast chromatin regulators ...


Biological And Physiological Condition Of Juvenile California Halibut (Paralichthys Californicus) Exposed To A Contamination Gradient In Mission Bay, Ca, Kevin Stolzenbach Dec 2014

Biological And Physiological Condition Of Juvenile California Halibut (Paralichthys Californicus) Exposed To A Contamination Gradient In Mission Bay, Ca, Kevin Stolzenbach

Theses

Contaminated sediments in marine environments have been shown to be good indicators of ecological risk and a means to assess anthropogenic impacts on marine habitats and the animals that inhabit them (Long et al. 1995, Rattner 2009). Estuarine sediments are especially complex media with regard to physical, chemical, and biological characteristics that trap, store, modify and sometimes release contaminants to the biota (Long et al. 1995). Especially vulnerable are animals that are in constant contact with the sediments, such as flatfishes that partially bury themselves for camouflage (Costa et al. 2011). Impacts can be assessed in a number of ways ...


Ethanol Modulation Of Mammalian Bk Channels In Excitable Tissues: Molecular Targets And Their Possible Contribution To Alcohol-Induced Altered Behavior, Alex M. Dopico, Anna N. Bukiya, Gilles E. Martin Dec 2014

Ethanol Modulation Of Mammalian Bk Channels In Excitable Tissues: Molecular Targets And Their Possible Contribution To Alcohol-Induced Altered Behavior, Alex M. Dopico, Anna N. Bukiya, Gilles E. Martin

University of Massachusetts Medical School Faculty Publications

In most tissues, the function of Ca(2+)- and voltage-gated K(+) (BK) channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naive preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of ...


Functional Characterization Of The Arginine Vasotocin 4 Receptor (Vt4r) In Sensory Circumventricular Organs Of The Chicken Gallus Gallus, Nguiessan Alphonse Aman Dec 2014

Functional Characterization Of The Arginine Vasotocin 4 Receptor (Vt4r) In Sensory Circumventricular Organs Of The Chicken Gallus Gallus, Nguiessan Alphonse Aman

Theses and Dissertations

Past studies have shown that the avian vasotocin 4 receptor (VT4R), homologous to the mammalian arginine vasopressin receptor 1a (V1aR/AVPR1A) is involved in immobilization stress. It was not known, however, whether the receptor is also associated with osmotic stress, and if so, what brain regions may be involved. Four treatment groups of chicks were used for the study. One group was subjected to 1h immobilization stress and two groups were administered intraperitoneal injection of 3 M NaCl or 0.15 M NaCl. One additional group served as controls. After 1 h, blood samples were taken for the determination of ...


Quantitative Analysis Of App Axonal Transport In Neurons: Role Of Jip1 In Enhanced App Anterograde Transport, Kyoko Chiba, Masahiko Araseki, Keisuke Nozawa, Keiko Furukori, Yoichi Araki, Takahide Matsushima, Tadashi Nakaya, Saori Hata, Yuhki Saito, Seiichi Uchida, Yasushi Okada, Angus C. Nairn, Roger J. Davis, Tohru Yamamoto, Masataka Kinjo, Hidenori Taru, Toshiharu Suzuki Nov 2014

Quantitative Analysis Of App Axonal Transport In Neurons: Role Of Jip1 In Enhanced App Anterograde Transport, Kyoko Chiba, Masahiko Araseki, Keisuke Nozawa, Keiko Furukori, Yoichi Araki, Takahide Matsushima, Tadashi Nakaya, Saori Hata, Yuhki Saito, Seiichi Uchida, Yasushi Okada, Angus C. Nairn, Roger J. Davis, Tohru Yamamoto, Masataka Kinjo, Hidenori Taru, Toshiharu Suzuki

Davis Lab Publications

Alzheimer's beta-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting protein 1 (JIP1); however, the role of JIP1 in APP transport by kinesin-1 in neurons remains unclear. We performed a quantitative analysis to understand the role of JIP1 in APP axonal transport. In JIP1-deficient neurons, we find that both the fast velocity ( approximately 2.7 mum/s) and high frequency (66%) of anterograde transport of APP cargo are impaired to a reduced velocity ( approximately 1.83 mum/s) and a lower frequency (45%). We identified two novel elements linked to JIP1 function, located in the central region of JIP1b ...


Differential Muscle Hypertrophy Is Associated With Satellite Cell Numbers And Akt Pathway Activation Following Activin Type Iib Receptor Inhibition In Mtm1 P.R69c Mice, Michael Lawlor, Marissa Viola, Hui Meng, Rachel Edelstein, Fujun Liu, Ke Yan, Elizabeth Luna, Alexandra Lerch-Gaggl, Raymond Hoffmann, Christopher Pierson, Anna Buj-Bello, Jennifer Lachey, Scott Pearsall, Lin Yang, Cecilia Hillard, Alan Beggs Oct 2014

Differential Muscle Hypertrophy Is Associated With Satellite Cell Numbers And Akt Pathway Activation Following Activin Type Iib Receptor Inhibition In Mtm1 P.R69c Mice, Michael Lawlor, Marissa Viola, Hui Meng, Rachel Edelstein, Fujun Liu, Ke Yan, Elizabeth Luna, Alexandra Lerch-Gaggl, Raymond Hoffmann, Christopher Pierson, Anna Buj-Bello, Jennifer Lachey, Scott Pearsall, Lin Yang, Cecilia Hillard, Alan Beggs

Elizabeth J. Luna

X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and ...


Comprehensive Identification Of Host Modulators Of Hiv-1 Replication Using Multiple Orthologous Rnai Reagents, Jian Zhu, Jill Perreira, Christopher R. Chin, Richard E. Baker, Louise Maranda, Stephen J. Elledge, Abraham L. Brass Oct 2014

Comprehensive Identification Of Host Modulators Of Hiv-1 Replication Using Multiple Orthologous Rnai Reagents, Jian Zhu, Jill Perreira, Christopher R. Chin, Richard E. Baker, Louise Maranda, Stephen J. Elledge, Abraham L. Brass

Open Access Articles

RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens performed with multiple orthologous RNAi reagents (MORR). In addition to being traditionally validated, the MORR screens and the historical HDF screens were quantitatively integrated by the adaptation of an established analysis program, RIGER, for the collective interpretation of each gene's phenotypic significance. False positives were addressed by the removal of poorly expressed candidates through gene expression ...


Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine Sep 2014

Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine

GSBS Dissertations and Theses

During each life cycle, gametes must preserve and pass on both genetic and epigenetic information, making the germline both immortal and totipotent. In the male germline the dramatic morphological transformation of a germ cell through meiosis, into a sperm competent for fertilization, while retaining this information is an incredible example of cellular differentiation. This process of spermatogenesis is inherently thermosensitive in numerous metazoa ranging from worms to man. Here, I describe the role of two redundant AGO-class paralogs, ALG-3/4, and their small RNA cofactors, in promoting thermotolerant male fertility in Caenorhabditis elegans. alg-3/4 double mutants exhibit temperature dependent ...


The Effect Of Maternal Aldosterone Levels On The Expression Of 11b-Hsd Isoenzymes In Normal And Hypertensive Rat Placentae, Nicole Jorissen Aug 2014

The Effect Of Maternal Aldosterone Levels On The Expression Of 11b-Hsd Isoenzymes In Normal And Hypertensive Rat Placentae, Nicole Jorissen

Journal of Undergraduate Research at Minnesota State University, Mankato

In this project, we developed a Western blotting procedure to semi-quantitate levels of 11β-HSD1 and 11β-HSD2 in whole cell extracts. Then, we applied this technique to analyze the effect of reduced maternal aldosterone levels on the expression of 11β-HSD1 and 11β-HSD2 isoenzymes in the placental tissue in both normal and hypertensive rats. These enzymes control levels of glucocorticoids which compete for aldosterone’s mineralocorticoid receptor. Overstimulation of this receptor results in hypertension. If aldosterone levels decrease, levels of the enzymes controlling active glucocorticoid concentrations might change to compensate for the lowered aldosterone levels. Decreased placental 11β-HSD2 expression could affect hypertension ...


Mirna-21 Has Anti-Inflammatory Effects In The Macrophage Response To Peritonitis., Rebecca Elise Barnett Aug 2014

Mirna-21 Has Anti-Inflammatory Effects In The Macrophage Response To Peritonitis., Rebecca Elise Barnett

Electronic Theses and Dissertations

This project investigated the role of miRNA-21 in the macrophage response to peritonitis; with the goal of understanding whether the associated mechanism has potential benefits in the clinical treatment of peritonitis. A novel therapeutic intervention in the treatment of peritonitis could modulate the host immune response to decrease an exaggerated pro-inflammatory innate response and then prevent or ameliorate the development of sepsis and organ failure. We found the following: 1. MiRNA-21 expression increases in peritoneal macrophages after lipopolysaccharide (LPS) stimulation. 2. Over expression of miRNA-21 decreases TNF-a secretion from macrophages after LPS stimulation. Suppression of miRNA-21 expression results in increased ...


Drosophila Sirt2/Mammalian Sirt3 Deacetylates Atp Synthase Beta And Regulates Complex V Activity, Motiur Rahman, Niraj K. Nirala, Alka Singh, Lihua Julie Zhu, Kaori Taguchi, Takeshi Bamba, Eiichiro Fukusaki, Leslie M. Shaw, David G. Lambright, Jairaj K. Acharya, Usha R. Acharya Jul 2014

Drosophila Sirt2/Mammalian Sirt3 Deacetylates Atp Synthase Beta And Regulates Complex V Activity, Motiur Rahman, Niraj K. Nirala, Alka Singh, Lihua Julie Zhu, Kaori Taguchi, Takeshi Bamba, Eiichiro Fukusaki, Leslie M. Shaw, David G. Lambright, Jairaj K. Acharya, Usha R. Acharya

Program in Gene Function and Expression Publications and Presentations

Adenosine triphosphate (ATP) synthase beta, the catalytic subunit of mitochondrial complex V, synthesizes ATP. We show that ATP synthase beta is deacetylated by a human nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, sirtuin 3, and its Drosophila melanogaster homologue, dSirt2. dsirt2 mutant flies displayed increased acetylation of specific Lys residues in ATP synthase beta and decreased complex V activity. Overexpression of dSirt2 increased complex V activity. Substitution of Lys 259 and Lys 480 with Arg in human ATP synthase beta, mimicking deacetylation, increased complex V activity, whereas substitution with Gln, mimicking acetylation, decreased activity. Mass spectrometry and proteomic experiments from ...


Calmodulation Meta-Analysis: Predicting Calmodulin Binding Via Canonical Motif Clustering, Karen Mruk, Brian M. Farley, Alan W. Ritacco, William R. Kobertz Jun 2014

Calmodulation Meta-Analysis: Predicting Calmodulin Binding Via Canonical Motif Clustering, Karen Mruk, Brian M. Farley, Alan W. Ritacco, William R. Kobertz

Biochemistry and Molecular Pharmacology Publications and Presentations

The calcium-binding protein calmodulin (CaM) directly binds to membrane transport proteins to modulate their function in response to changes in intracellular calcium concentrations. Because CaM recognizes and binds to a wide variety of target sequences, identifying CaM-binding sites is difficult, requiring intensive sequence gazing and extensive biochemical analysis. Here, we describe a straightforward computational script that rapidly identifies canonical CaM-binding motifs within an amino acid sequence. Analysis of the target sequences from high resolution CaM-peptide structures using this script revealed that CaM often binds to sequences that have multiple overlapping canonical CaM-binding motifs. The addition of a positive charge discriminator ...


Activin Limits Progenitor Capability By Promoting Epithelial Cell Differentiation In The Mammary Gland, Karen A. Dunphy, Thiruppavai Chandrasekaran, Niraj Bhatt, Michelle Chen, Amy L. Roberts, Mary Hagen, D. Joseph Jerry May 2014

Activin Limits Progenitor Capability By Promoting Epithelial Cell Differentiation In The Mammary Gland, Karen A. Dunphy, Thiruppavai Chandrasekaran, Niraj Bhatt, Michelle Chen, Amy L. Roberts, Mary Hagen, D. Joseph Jerry

UMass Center for Clinical and Translational Science Research Retreat

Transforming growth factor beta (TGF-beta) and activin utilize common signaling pathways, via smad2/3 and smad4, to mediate tumor suppression by effecting cell cycle arrest and apoptosis. Differences in temporal expression patterns suggest that each cytokine has specific roles in mammary gland development. Activin is expressed during pregnancy and lactation and is required for branching and lactogenesis, implying a role in mammary gland maturation. In contrast, TGF-beta is expressed during involution during mammary gland regression and functions to re-organize the mammary epithelial content to the non-lactating state. Previously, we found that TGF-beta and activin do share common signaling pathways allowing ...


Fluorescent Probes For Molecular Imaging Of Ros/Rns Species In Living Systems, Maolin Guo, Yibin Wei, Weiqi Yang, Xiaofei Fu, Yi Zhang, Bing Yan May 2014

Fluorescent Probes For Molecular Imaging Of Ros/Rns Species In Living Systems, Maolin Guo, Yibin Wei, Weiqi Yang, Xiaofei Fu, Yi Zhang, Bing Yan

UMass Center for Clinical and Translational Science Research Retreat

Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) are highly reactive species which play crucial roles in many fundamental physiological processes including cellular signalling pathways. Over-production of these reactive species by various stimuli leads to cellular oxidative stress which is linked to various disease conditions. Therefore, the development of novel detection methods for ROS and RNS is of great interest and indispensable for monitoring the dynamic changes of ROS and RNS in cells and for elucidating their mechanisms of trafficking and connections to diseases. We have been recently developing various fluorescent sensors which can selectively detect metal ions, ROS ...


Mice Deficient In Sfrp1 Exhibit Increased Adiposity, Dysregulated Glucose Metabolism, Lotfi M. Bassa, Kelly J. Gauger, Elizabeth M. Henchey, Melissa Brown, Sallie S. Schneider May 2014

Mice Deficient In Sfrp1 Exhibit Increased Adiposity, Dysregulated Glucose Metabolism, Lotfi M. Bassa, Kelly J. Gauger, Elizabeth M. Henchey, Melissa Brown, Sallie S. Schneider

UMass Center for Clinical and Translational Science Research Retreat

The molecular mechanisms involved in the development of obesity and related complications remain unclear. Wnt signaling plays an important role in preadipocyte differentiation and adipogenesis. The expression of a Wnt antagonist, secreted frizzled related protein 1 (SFRP1), is increased in response to initial weight gain, then levels are reduced under conditions of extreme obesity in both humans and animals. Here we report that loss of Sfrp1 exacerbates weight gain and glucose homeostasis in mice in response to diet induced obesity (DIO). Sfrp1-/- mice fed a high fat diet (HFD) exhibited an increase in body mass accompanied by increases in body ...


Epigenetic Modifications Associated With Aortic Remodeling In Hyperhomocysteinemia., Nithya Narayanan May 2014

Epigenetic Modifications Associated With Aortic Remodeling In Hyperhomocysteinemia., Nithya Narayanan

Electronic Theses and Dissertations

Background: Hyperhomocysteinemia (HHcy) is prevalent in hypertensive patients and is an independent risk factor for aortic pathologies. HHcy is known to cause an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) leading to accumulation of collagen in the aorta resulting in stiffness and development of hypertension. Although the exact mechanism of extracellular matrix remodeling (ECM) is unclear, emerging evidence implicates epigenetic regulation involving DNA methylation. The purpose of the study was to investigate whether inhibition of DNA methylation reduces high blood pressure by regulating aortic ECM remodeling in HHcy. Methods: In the first set of experiments, we ...


Myocyte-Specific Overexpression Of Stromal Cell-Derived Factor 1 Facilitates Cardiac Regeneration And Improves Myocardial Function After Infarction In Mice., Detlef Ernst-Rudolf Obal May 2014

Myocyte-Specific Overexpression Of Stromal Cell-Derived Factor 1 Facilitates Cardiac Regeneration And Improves Myocardial Function After Infarction In Mice., Detlef Ernst-Rudolf Obal

Electronic Theses and Dissertations

Background: Interruption of cardiac stromal cell-derived factor 1 (SDF1)-CXCR4 axis by chronic AMD3100 administration increased myocardial injury after permanent coronary artery ligation, demonstrating the important role of this chemokine in cardiac regeneration. Hypothesis: Cardiomyocyte-specific conditional overexpression of SDF prevents heart failure after permanent coronary ligation and facilitates cardiac regeneration. Methods and Results: Tetracycline-controlled, a-myosine heavy chain promoter directed overexpression of cardiac SDF resulted in a significant increase of SDF expression (SDF: 8.1 ng / g protein) compared with littermate WT mice (0.02 ng / g protein) four weeks after doxycycline withdrawal. SDF overexpression increased AKT and casein kinase 1 ...


Inflammation-Resolving Lipid Mediators Promote Revascularization To Enhance Wound Healing., Michael Jingyuan Zhang May 2014

Inflammation-Resolving Lipid Mediators Promote Revascularization To Enhance Wound Healing., Michael Jingyuan Zhang

Electronic Theses and Dissertations

Wound healing is a highly concerted cellular process that begins with inflammation and proceeds to resolution to revascularize the site of injury. Although inflammation is essential to revascularization during wound healing, it is now recognized that resolution is an active process that is equally important. Other investigations have implicated a beneficial effect of resolving inflammation and promoting resolution in the remission of inflammatory pathologies. Recently investigations have yielded a novel class of ?-3 fatty acid derived lipid mediators, biosynthesized by leukocytes, which are capable of resolving inflammation and promoting resolution. We therefore hypothesized that these leukocyte-derived pro-resolving lipid mediators can ...


The Anti-Obesogenic Effects Of Nitric Oxide., Brian Edward Sansbury 1985- May 2014

The Anti-Obesogenic Effects Of Nitric Oxide., Brian Edward Sansbury 1985-

Electronic Theses and Dissertations

Obesity is a strong risk factor for developing type 2 diabetes and cardiovascular disease and has quickly reached epidemic proportions with few tangible and safe treatment options. While it is generally accepted that the primary cause of obesity is energy imbalance, i.e., more calories are consumed than are utilized, understanding how caloric balance is regulated has proven a challenge. Molecular processes and pathways that directly regulate energy metabolism represent promising targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of obesity ...


Phthalates And Phthalate Alternatives: Effects On Proliferative And Estrogenic Target Genes In Ishikawa Cells, Ranjani Sundar '15, Ping Yin, Serdar E. Bulun May 2014

Phthalates And Phthalate Alternatives: Effects On Proliferative And Estrogenic Target Genes In Ishikawa Cells, Ranjani Sundar '15, Ping Yin, Serdar E. Bulun

Student Publications & Research

Phthalates are used as plasticizers in many of the products found in medical, household, and industrial applications. Much research has not been completed on the effects of these phthalates as potential endocrine disrupting chemicals (EDCs). As these chemicals are ingested, the mechanism by which they affect the reproductive system is largely unknown. The purpose of this study was to observe how 2 phthalates, Di-n-butyl phthalate (DBP) and Diisononyl phthalate (DINP), and 2 phthalate alternatives, Dioctyl terephthalate (DOTP) and BHT (butylated hydroxytoluene)affect uterine cells in comparison to a vehicle treatment and 17β-Estradiol treatment. Changes in expression of mRNA were observed ...


Mnk2 Alternative Splicing Modulates The P38-Mapk Pathway And Impacts Ras-Induced Transformation, Avraham Maimon, Maxim Mogilevsky, Asaf Shilo, Regina Golan-Gerstl, Akram Obiedat, Vered Ben-Hur, Ilana Lebenthal-Loinger, Ilan Stein, Reuven Reich, Jonah Beenstock, Eldar Zehorai, Claus L. Andersen, Kasper Thorsen, Torben F. Orntoft, Roger J. Davis, Ben Davidson, David Mu, Rotem Karni Apr 2014

Mnk2 Alternative Splicing Modulates The P38-Mapk Pathway And Impacts Ras-Induced Transformation, Avraham Maimon, Maxim Mogilevsky, Asaf Shilo, Regina Golan-Gerstl, Akram Obiedat, Vered Ben-Hur, Ilana Lebenthal-Loinger, Ilan Stein, Reuven Reich, Jonah Beenstock, Eldar Zehorai, Claus L. Andersen, Kasper Thorsen, Torben F. Orntoft, Roger J. Davis, Ben Davidson, David Mu, Rotem Karni

Davis Lab Publications

The kinase Mnk2 is a substrate of the MAPK pathway and phosphorylates the translation initiation factor eIF4E. In humans, MKNK2, the gene encoding for Mnk2, is alternatively spliced yielding two splicing isoforms with differing last exons: Mnk2a, which contains a MAPK-binding domain, and Mnk2b, which lacks it. We found that the Mnk2a isoform is downregulated in breast, lung, and colon tumors and is tumor suppressive. Mnk2a directly interacts with, phosphorylates, activates, and translocates p38alpha-MAPK into the nucleus, leading to activation of its target genes, increasing cell death and suppression of Ras-induced transformation. Alternatively, Mnk2b is pro-oncogenic and does not activate ...


An Integrated Structural Mechanism For Relief Of Autoinhibition And Membrane Targeting In Cytohesin Family Guanine Nucleotide Exchange Factors: A Dissertation, Andrew W. Malaby Apr 2014

An Integrated Structural Mechanism For Relief Of Autoinhibition And Membrane Targeting In Cytohesin Family Guanine Nucleotide Exchange Factors: A Dissertation, Andrew W. Malaby

GSBS Dissertations and Theses

Guanine nucleotide exchange factors (GEFs) regulate and organize diverse cellular processes through their role in converting GTPases from the inactive GDP bound state to the active GTP bound state. An increasing number of GEFs undergo autoregulatory mechanisms through complex intramolecular interactions. Relief of autoinhibition involves specific phosphorylation or binding to lipid and/or effector proteins at sites distal from the catalytic domain, and is often coupled to membrane recruitment. In Cytohesin Arf GEFs, the catalytic Sec7 domain is autoinhibited by a linker region and C-terminal helix flanking a Pleckstrin Homology (PH) domain. Upon binding of the PH domain to low ...


Transcriptional Regulation Of Caenorhabditis Elegans Foxo/Daf-16 Modulates Lifespan, Ankita Bansal, Eun-Soo Kwon, Darryl Conte Jr., Haibo Liu, Michael J. Gilchrist, Lesley T. Macneil, Heidi A. Tissenbaum Apr 2014

Transcriptional Regulation Of Caenorhabditis Elegans Foxo/Daf-16 Modulates Lifespan, Ankita Bansal, Eun-Soo Kwon, Darryl Conte Jr., Haibo Liu, Michael J. Gilchrist, Lesley T. Macneil, Heidi A. Tissenbaum

Program in Gene Function and Expression Publications and Presentations

BACKGROUND: Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is the primary target of insulin/IGF-1 signaling, and multiple isoforms of DAF-16 (a, b, and d/f) modulate lifespan, metabolism, dauer formation, and stress resistance. Thus far, across phylogeny modulation of mammalian FOXOs and DAF-16 have focused on post-translational regulation with little focus on transcriptional regulation. In C. elegans, we have previously shown that DAF-16d/f cooperates with DAF-16a to promote longevity. In this study, we generated transgenic strains expressing near-endogenous levels of either daf-16a or ...


Ifitm3 Restricts Influenza A Virus Entry By Blocking The Formation Of Fusion Pores Following Virus-Endosome Hemifusion, Tanay M. Desai, Mariana Marin, Christopher R. Chin, George Savidis, Abraham L. Brass, Gregory B. Melikyan Apr 2014

Ifitm3 Restricts Influenza A Virus Entry By Blocking The Formation Of Fusion Pores Following Virus-Endosome Hemifusion, Tanay M. Desai, Mariana Marin, Christopher R. Chin, George Savidis, Abraham L. Brass, Gregory B. Melikyan

University of Massachusetts Medical School Faculty Publications

Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral ...


Kidney Stones And The Zip10 Transporter: An Analysis Of Calcium Oxalate Stone Formation Using Frog And Fruit Fly Models, Paige Williams Apr 2014

Kidney Stones And The Zip10 Transporter: An Analysis Of Calcium Oxalate Stone Formation Using Frog And Fruit Fly Models, Paige Williams

Life and Environmental Sciences Undergraduate Theses

Kidney stones are a health ailment (~1% population occurrence), yet the mechanism and initiation of stone formation remains incompletely explained. Calcium oxalate (CaOx) stones seem to initially form on sites called Randall’s Plaques that are high in zinc content. A suggested correlation between stone disease and the Zip10 transporter in a GWAS (genome wide association study) on Miniature Schnauzers allowed me to investigate the role of zinc and Zip10 on CaOx stone formation. Our results from radioactive 63Zn uptakes in injected frog (Xenopus laevis) oocytes indicate that (human, canine and Drosophila) Zip10 transport Zn2+. The Zip10 clones had highest ...


Fus/Tls In Stress Response - Implications For Amyotrophic Lateral Sclerosis: A Dissertation, Reddy Ranjith Kumar Sama Mar 2014

Fus/Tls In Stress Response - Implications For Amyotrophic Lateral Sclerosis: A Dissertation, Reddy Ranjith Kumar Sama

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease is a fatal neurodegenerative disease. ALS is typically adult onset and is characterized by rapidly progressive loss of both upper and lower motor neurons that leads to death usually within 3-5 years. About 90% of all the cases are sporadic with no family history while the remaining 10% are familial cases with mutations in several genes including SOD1, FUS/TLS, TDP43 and C9ORF72.

FUS/TLS (Fused in Sarcoma/Translocated in Liposarcoma or FUS) is an RNA/DNA binding protein that is involved in multiple cellular functions including DNA damage ...


Analyses Of All Possible Point Mutations Within A Protein Reveals Relationships Between Function And Experimental Fitness: A Dissertation, Benjamin P. Roscoe Mar 2014

Analyses Of All Possible Point Mutations Within A Protein Reveals Relationships Between Function And Experimental Fitness: A Dissertation, Benjamin P. Roscoe

GSBS Dissertations and Theses

The primary amino acid sequence of a protein governs its specific cellular functions. Since the cracking of the genetic code in the late 1950’s, it has been possible to predict the amino acid sequence of a given protein from the DNA sequence of a gene. Nevertheless, the ability to predict a protein’s function from its primary sequence remains a great challenge in biology. In order to address this problem, we combined recent advances in next generation sequencing technologies with systematic mutagenesis strategies to assess the function of thousands of protein variants in a single experiment. Using this strategy ...


Ceramide Transfer Protein Deficiency Compromises Organelle Function And Leads To Senescence In Primary Cells, Raghavendra Pralhada Rao, Luana Scheffer, Sargur M. Srideshikan, Velayoudame Parthibane, Teresa Kosakowska-Cholody, M. Athar Masood, Kunio Nagashima, Prabhakar Gudla, Stephen Lockett, Usha Acharya, Jairaj K. Acharya Mar 2014

Ceramide Transfer Protein Deficiency Compromises Organelle Function And Leads To Senescence In Primary Cells, Raghavendra Pralhada Rao, Luana Scheffer, Sargur M. Srideshikan, Velayoudame Parthibane, Teresa Kosakowska-Cholody, M. Athar Masood, Kunio Nagashima, Prabhakar Gudla, Stephen Lockett, Usha Acharya, Jairaj K. Acharya

Program in Gene Function and Expression Publications and Presentations

Ceramide transfer protein (CERT) transfers ceramide from the endoplasmic reticulum (ER) to the Golgi complex. Its deficiency in mouse leads to embryonic death at E11.5. CERT deficient embryos die from cardiac failure due to defective organogenesis, but not due to ceramide induced apoptotic or necrotic cell death. In the current study we examined the effect of CERT deficiency in a primary cell line, namely, mouse embryonic fibroblasts (MEFs). We show that in MEFs, unlike in mutant embryos, lack of CERT does not lead to increased ceramide but causes an accumulation of hexosylceramides. Nevertheless, the defects due to defective sphingolipid ...


Impact Of Obesity On Ovotoxicity Induced By 7,12-Dimethylbenz[A]Anthracene In Mice, Jackson Nteeba, Shanthi Ganesan, Aileen F. Keating Mar 2014

Impact Of Obesity On Ovotoxicity Induced By 7,12-Dimethylbenz[A]Anthracene In Mice, Jackson Nteeba, Shanthi Ganesan, Aileen F. Keating

Animal Science Publications

Insulin, elevated during obesity, regulates xenobiotic biotransformation enzymes, potentially through phosphatidylinositol 3-kinase (PI3K) signaling, in extraovarian tissues. PI3K regulates oocyte viability, follicular activation, and ovarian chemical biotransformation. 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen and ovotoxicant, destroys all stages of follicles, leading to premature ovarian failure. Obesity has been reported to promote DMBA-induced tumors, but it remains unknown whether obesity affects ovarian xenobiotic metabolism. Therefore, we investigated ovarian expression of xenobiotic metabolism genes—microsomal epoxide hydrolase (Ephx1), glutathione S-transferase (GST) class Pi (Gstp1) and class mu 1 (Gstm1), and PI3K-signaling members (protein kinase B [AKT] alpha [Akt1], beta [Akt2], and ...


Myosin-Binding Protein C Displaces Tropomyosin To Activate Cardiac Thin Filaments And Governs Their Speed By An Independent Mechanism, Ji Young Mun, Michael J. Previs, Hope Y. Yu, James Gulick, Larry S. Tobacman, Samantha Beck Previs, Jeffrey Robbins, David M. Warshaw, Roger Craig Feb 2014

Myosin-Binding Protein C Displaces Tropomyosin To Activate Cardiac Thin Filaments And Governs Their Speed By An Independent Mechanism, Ji Young Mun, Michael J. Previs, Hope Y. Yu, James Gulick, Larry S. Tobacman, Samantha Beck Previs, Jeffrey Robbins, David M. Warshaw, Roger Craig

Craig Lab Publications

Myosin-binding protein C (MyBP-C) is an accessory protein of striated muscle thick filaments and a modulator of cardiac muscle contraction. Defects in the cardiac isoform, cMyBP-C, cause heart disease. cMyBP-C includes 11 Ig- and fibronectin-like domains and a cMyBP-C-specific motif. In vitro studies show that in addition to binding to the thick filament via its C-terminal region, cMyBP-C can also interact with actin via its N-terminal domains, modulating thin filament motility. Structural observations of F-actin decorated with N-terminal fragments of cMyBP-C suggest that cMyBP-C binds to actin close to the low Ca(2+) binding site of tropomyosin. This suggests that ...