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University of Massachusetts Medical School

Cellular and Molecular Physiology

2014

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Articles 1 - 30 of 49

Full-Text Articles in Life Sciences

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 ...


Higher-Order Unfolding Of Peri/Centric Satellite Heterochromatin Is An Early And Consistent Event In Cell Senescence: A Dissertation, Eric C. Swanson Dec 2014

Higher-Order Unfolding Of Peri/Centric Satellite Heterochromatin Is An Early And Consistent Event In Cell Senescence: A Dissertation, Eric C. Swanson

GSBS Dissertations and Theses

Cellular senescence is thought to play an essential role in many biological functions including tumor suppression and organismal aging. Senescent cells, which are permanently removed from the cell cycle, can be found both in vivo in many different tissue types and in vitro within cultures of non-immortalized cells. Despite their inability to proliferate, these cells persist and remain metabolically active for indefinite periods of time. This physiologic process occurs in response to a variety of cellular insults including oxidative stress, shortened telomeres, constitutive oncogene expression, and DNA damage, and can be initiated by upregulation of one of the two known ...


A Calcium-Dependent Protease As A Potential Therapeutic Target For Wolfram Syndrome, Simin Lu, Clay F. Semenkovich, Peter A. Greer, Fumihiko Urano Dec 2014

A Calcium-Dependent Protease As A Potential Therapeutic Target For Wolfram Syndrome, Simin Lu, Clay F. Semenkovich, Peter A. Greer, Fumihiko Urano

GSBS Student Publications

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced ...


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 ...


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 ...


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 ...


Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis In Drosophila, Alla Amcheslavsky, Wei Song, Qi Li, Yingchao Nie, Ivan Bragatto, Dominique Ferrandon, Norbert Perrimon, Y. Tony Ip Oct 2014

Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis In Drosophila, Alla Amcheslavsky, Wei Song, Qi Li, Yingchao Nie, Ivan Bragatto, Dominique Ferrandon, Norbert Perrimon, Y. Tony Ip

UMass Center for Clinical and Translational Science Supported Publications

Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing ...


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 ...


Il-1 Signaling In Obesity-Induced Hepatic Lipogenesis And Steatosis, Kimberly A. Negrin, Rachel J. Roth Flach, Marina T. Distefano, Anouch Matevossian, Randall H. Friedline, Dae Young Jung, Jason K. Kim, Michael P. Czech Sep 2014

Il-1 Signaling In Obesity-Induced Hepatic Lipogenesis And Steatosis, Kimberly A. Negrin, Rachel J. Roth Flach, Marina T. Distefano, Anouch Matevossian, Randall H. Friedline, Dae Young Jung, Jason K. Kim, Michael P. Czech

Open Access Articles

Non-alcoholic fatty liver disease is prevalent in human obesity and type 2 diabetes, and is characterized by increases in both hepatic triglyceride accumulation (denoted as steatosis) and expression of pro-inflammatory cytokines such as IL-1beta. We report here that the development of hepatic steatosis requires IL-1 signaling, which upregulates Fatty acid synthase to promote hepatic lipogenesis. Using clodronate liposomes to selectively deplete liver Kupffer cells in ob/ob mice, we observed remarkable amelioration of obesity-induced hepatic steatosis and reductions in liver weight, triglyceride content and lipogenic enzyme expressions. Similar results were obtained with diet-induced obese mice, although visceral adipose tissue macrophage ...


Cx3cl1 (Fractalkine) Protein Expression In Normal And Degenerating Mouse Retina: In Vivo Studies, Marina Zieger, Peter K. Ahnelt, Pavel Uhrin Sep 2014

Cx3cl1 (Fractalkine) Protein Expression In Normal And Degenerating Mouse Retina: In Vivo Studies, Marina Zieger, Peter K. Ahnelt, Pavel Uhrin

Open Access Articles

We aimed to investigate fractalkine (CX3CL1) protein expression in wild type (wt) retina and its alterations during retinal degeneration in mouse model (rd10) of retinitis pigmentosa. Forms of retinal protein CX3CL1, total protein and mRNA levels of CX3CL1 were analyzed at postnatal days (P) 5, 10, 14, 22, 30, 45, and 60 by Western blotting and real-time PCR. Cellular sources of CX3CL1 were investigated by in situ hybridization histochemistry (ISH) and using transgenic (CX3CL1cherry) mice. The immunoblots revealed that in both, wt and rd10 retinas, a membrane integrated approximately 100 kDa CX3CL1 form and a cleaved approximately 85 kDa CX3CL1 ...


Tlr Sorting By Rab11 Endosomes Maintains Intestinal Epithelial-Microbial Homeostasis, Shiyan Yu, Yingchao Nie, Y. Tony Ip, Nan Gao Sep 2014

Tlr Sorting By Rab11 Endosomes Maintains Intestinal Epithelial-Microbial Homeostasis, Shiyan Yu, Yingchao Nie, Y. Tony Ip, Nan Gao

UMass Center for Clinical and Translational Science Supported Publications

Compartmentalization of Toll-like receptors (TLRs) in intestinal epithelial cells (IECs) regulates distinct immune responses to microbes; however, the specific cellular machinery that controls this mechanism has not been fully identified. Here we provide genetic evidences that the recycling endosomal compartment in enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in Drosophila midgut caused epithelial cell-intrinsic cytokine production, inflammatory bowel phenotype, and early mortality. Unlike wild-type controls, germ-free Rab11a-deficient mouse intestines failed ...


Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock Aug 2014

Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock

Open Access Articles

When cells die by necrosis in vivo they stimulate an inflammatory response. It is thought that this response is triggered when the injured cells expose proinflammatory molecules, collectively referred to as damage associated molecular patterns (DAMPs), which are recognized by cells or soluble molecules of the innate or adaptive immune system. Several putative DAMPs and/or their receptors have been identified, but whether and how much they participate in responses in vivo is incompletely understood, and they have not previously been compared side-by-side in the same models. This study focuses on evaluating the contribution of multiple mechanisms that have been ...


A Deterministic Model Predicts The Properties Of Stochastic Calcium Oscillations In Airway Smooth Muscle Cells, Pengxing Cao, Xiahui Tan, Graham Donovan, Michael J. Sanderson, James Sneyd Aug 2014

A Deterministic Model Predicts The Properties Of Stochastic Calcium Oscillations In Airway Smooth Muscle Cells, Pengxing Cao, Xiahui Tan, Graham Donovan, Michael J. Sanderson, James Sneyd

Open Access Articles

The inositol trisphosphate receptor ([Formula: see text]) is one of the most important cellular components responsible for oscillations in the cytoplasmic calcium concentration. Over the past decade, two major questions about the [Formula: see text] have arisen. Firstly, how best should the [Formula: see text] be modeled? In other words, what fundamental properties of the [Formula: see text] allow it to perform its function, and what are their quantitative properties? Secondly, although calcium oscillations are caused by the stochastic opening and closing of small numbers of [Formula: see text], is it possible for a deterministic model to be a reliable ...


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 ...


Dicer Cooperates With P53 To Suppress Dna Damage And Skin Carcinogenesis In Mice, Stephen Lyle, Kathleen Hoover, Cansu Colpan, Zhiqing Zhu, Zdenka Matijasevic, Stephen N. Jones Jun 2014

Dicer Cooperates With P53 To Suppress Dna Damage And Skin Carcinogenesis In Mice, Stephen Lyle, Kathleen Hoover, Cansu Colpan, Zhiqing Zhu, Zdenka Matijasevic, Stephen N. Jones

University of Massachusetts Medical School Faculty Publications

Dicer is required for the maturation of microRNA, and loss of Dicer and miRNA processing has been found to alter numerous biological events during embryogenesis, including the development of mammalian skin and hair. We have previously examined the role of miRNA biogenesis in mouse embryonic fibroblasts and found that deletion of Dicer induces cell senescence regulated, in part, by the p53 tumor suppressor. Although Dicer and miRNA molecules are thought to have either oncogenic or tumor suppressing roles in various types of cancer, a role for Dicer and miRNAs in skin carcinogenesis has not been established. Here we show that ...


Hdac4 Integrates Pth And Sympathetic Signaling In Osteoblasts, Arnaud Obri, Munevver Parla. Makinistoglu, Hong Zhang, Gerard Karsenty Jun 2014

Hdac4 Integrates Pth And Sympathetic Signaling In Osteoblasts, Arnaud Obri, Munevver Parla. Makinistoglu, Hong Zhang, Gerard Karsenty

Cell and Developmental Biology Publications

Parathyroid hormone (PTH) and the sympathetic tone promote Rankl expression in osteoblasts and osteoclast differentiation by enhancing cyclic adenosine monophosphate production through an unidentified transcription factor for PTH and through ATF4 for the sympathetic tone. How two extracellular cues using the same second messenger in the same cell elicit different transcriptional events is unknown. In this paper, we show that PTH favors Rankl expression by triggering the ubiquitination of HDAC4, a class II histone deacetylase, via Smurf2. HDAC4 degradation releases MEF2c, which transactivates the Rankl promoter. Conversely, sympathetic signaling in osteoblasts favors the accumulation of HDAC4 in the nucleus and ...


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 ...


High Performance Amphiphilic Polymer/Hydroxyapatite Composite Tissue Scaffolds, Artem B. Kutikov, Jie Song May 2014

High Performance Amphiphilic Polymer/Hydroxyapatite Composite Tissue Scaffolds, Artem B. Kutikov, Jie Song

UMass Center for Clinical and Translational Science Research Retreat

There is a critical clinical need for alternatives to autograft and allograft bone for over 500,000 bone grafting operations performed each year in the United States. Current synthetic bone grafts suffer from poor handling characteristics, brittle mechanical properties, and inconsistent bioactivity. By blending a biodegradable amphiphilic polymer with hydroxyapatite (HA), the main mineral component in bone, we developed an improved synthetic bone graft. The polymer/HA composites were fabricated in both 2-D and 3-D forms by electrospinning and 3-D printing. These materials exhibited unique handling characteristics such as high tensile elasticity (>200% failure strain) and self-stiffening properties upon hydration ...


Pericyte Nf-Κb Activation Enhances Endothelial Cell Proliferation And Proangiogenic Cytokine Secretion, Katherine E. Labarbera, Robert D. Hyldahl, Sarah Witkowski May 2014

Pericyte Nf-Κb Activation Enhances Endothelial Cell Proliferation And Proangiogenic Cytokine Secretion, Katherine E. Labarbera, Robert D. Hyldahl, Sarah Witkowski

UMass Center for Clinical and Translational Science Research Retreat

Pericytes are skeletal muscle resident, multipotent stem cells that are localized to capillaries. They respond to damage through activation of nuclear-factor kappa-B (NF-κB), a transcription factor that regulates many cellular processes including inflammation. Research has shown that pericyte NF-κB activation positively affects myoblast proliferation. It is unknown how pericyte NF-κB affects signaling and proliferation of endothelial cells, an important component of muscle tissue microcirculation.

PURPOSE: To determine the effects of altered pericyte NF-κB activity on endothelial cell proliferation and identify inflammatory factors involved in this cell-cell signaling.

METHODS: Human primary pericytes were transfected with vectors designed to increase or decrease ...


Exosome-Mediated Delivery Of Rna Interference And Mirna Mimic, Fatemeh Momen-Heravi, Shashi Bala, Terence N. Bukong, Gyongyi Szabo May 2014

Exosome-Mediated Delivery Of Rna Interference And Mirna Mimic, Fatemeh Momen-Heravi, Shashi Bala, Terence N. Bukong, Gyongyi Szabo

UMass Center for Clinical and Translational Science Research Retreat

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules and play pivotal roles in both physiological intercellular crosstalk and disease pathogenesis. Here, we showed that B cell-derived exosomes can function as vehicles to deliver exogenous miRNA-155 mimic or inhibitor into hepatocytes or macrophages, respectively. Stimulation of B cells significantly increased exosome production. Unlike in parental cells, baseline level of miRNA-155 was very low in exosomes derived from stimulated B cells. Exosomes loaded with a miRNA-155 mimic significantly increased miRNA-155 levels in primary mouse hepatocytes and the liver of miRNA-155 knockout mice. Treatment of RAW macrophages with miRNA-155 inhibitor loaded exosomes resulted in statistically ...


Associations Of Adipose Tissue Architecture, Adipokines And Inflammatory Markers With Body Mass Index And Gestational Weight Gain In Non-Diabetic Pregnancies, Tiffany A. Moore Simas, Crina Boeras, Ningning Zhang, Olga Gaelikman, Katherine G. Leung, Nicole M. Wedick, Laura Robidoux, Jodi Adams Puleo, Mary M. Lee, Silvia Corvera, Milagros C. Rosal May 2014

Associations Of Adipose Tissue Architecture, Adipokines And Inflammatory Markers With Body Mass Index And Gestational Weight Gain In Non-Diabetic Pregnancies, Tiffany A. Moore Simas, Crina Boeras, Ningning Zhang, Olga Gaelikman, Katherine G. Leung, Nicole M. Wedick, Laura Robidoux, Jodi Adams Puleo, Mary M. Lee, Silvia Corvera, Milagros C. Rosal

UMass Center for Clinical and Translational Science Research Retreat

Background: Some pregnancy weight gain is stored as adipose tissue (AT). Human AT depots vary in their capacity for expansion. Data suggests that subcutaneous (SQ) is adapted for healthy lipid storage. Conversely visceral (V) accumulation is associated with inflammation, obesity-related co-morbidities and Type 2 diabetes (T2DM) risk. We investigated SQ and VAT histologic architecture along with insulin, adipokines and inflammatory markers in relationship to prepregnancy BMI and gestational weight gain (GWG).

Methods: Subset of non-diabetic singleton gravidas from the Pregnancy & Postpartum Observational Dietary Study (PPODS), undergoing Cesareans and consenting to SQ & VAT biopsies were included. Average adipocyte size assessed in10 sections/depot/subject. Maternal and cord blood insulin, adiponectin, leptin, PAI-1, CRP, TNFα, IL1b, IL6 and IL8 evaluated using Luminex MAGPIX, laser based fluorescent analytical test instrumentation with MILLIPLEX® multi-analyte panels. GWG determined by difference in pre-pregnancy and last prenatal visit weight.

Results: Of 110 subjects enrolled, 19 (17.3%) delivered by Cesarean with 14 consenting to AT sampling, and 7 (50%) having both SQ and VAT available for analysis. These 7 had mean pre-pregnancy BMI 27.8±5.6 kg/m2 and GWG 50.0±25.7 lb (range 19-83) with delivery age 39.2±0.7 wks. Mean SQ and VAT adipocyte sizes were 2892±716 pixels2 (range 1866-3775) and 2427±641 pixels2 (range 1416-3397) respectively (p=0.310); neither were statistically correlated with BMI or GWG. Pre-pregnancy BMI statistically correlated with maternal serum insulin (0.786, p=0 ...


The Effects Of Rhodiola Crenulata Extract On Proliferation And Differentiation In Glioblastoma Multiforme, Maria Carmen Mora, Kaitlyn Wong, Michael Tirabassi, Richard Arenas, Sallie S. Schneider May 2014

The Effects Of Rhodiola Crenulata Extract On Proliferation And Differentiation In Glioblastoma Multiforme, Maria Carmen Mora, Kaitlyn Wong, Michael Tirabassi, Richard Arenas, Sallie S. Schneider

UMass Center for Clinical and Translational Science Research Retreat

Purpose: Purpose of the study was to evaluate the effects of rhodiola crenulata plant extract on glioblastoma in vitro. Methods: U-87MG glioblastoma multiforme cell line was utilized for evaluation in this study. Cells were treated with 100ug/ml or 200ug/ml of rhodiola crenulata and compared to ethanol vehicle control. Proliferation was measured at 24, 48, 72, and 96 hours after treatment utilizing an MTS proliferation assay. To further assess proliferation a clonogenicity assay was conducted. These cells were treated with ethanol vehicle control, 100ug/ml of rhodiola, radiation, or combined rhodiola/radiation treatment. To evaluate differentiation the expression of ...


Anti-Ppkcθ (T538) Delivery Via Cell Penetrating Peptide Mimics As A Novel Treatment Of Aplastic Anemia, Emrah Ilker Ozay, Gabriela Gonzalez-Perez, Joe Torres, Gregory N. Tew, Lisa M. Minter May 2014

Anti-Ppkcθ (T538) Delivery Via Cell Penetrating Peptide Mimics As A Novel Treatment Of Aplastic Anemia, Emrah Ilker Ozay, Gabriela Gonzalez-Perez, Joe Torres, Gregory N. Tew, Lisa M. Minter

UMass Center for Clinical and Translational Science Research Retreat

The objective of this study is to deliver anti-pPKCθ (T538) into T cells (hPBMCs) by using cell penetrating peptide mimics (CPPMs) to neutralize PKCθ activity both in vitro and in vivo, with the eventual goal of treating aplastic anemia (AA). AA is an immune-mediated bone marrow failure disease caused by T helper type 1 (Th1) autoimmune responses, which destroy blood cell progenitors. It was previously reported that protein kinase C theta (PKCθ), expressed specifically in T cells, plays an important role in T cell signaling by mediating Th1 differentiation. Mice treated with Rottlerin, a pharmacological inhibitor of PKCθ, are rescued ...


Ablation Of Raf-1 Kinase Inhibitory Protein (Rkip) Improves Photoreceptor Structure And Function In A Cep290-Mutant Mouse Model Of Severe Retinal Degeneration, Balajikarthick Subramanian, Manisha Anand, Hemant Khanna May 2014

Ablation Of Raf-1 Kinase Inhibitory Protein (Rkip) Improves Photoreceptor Structure And Function In A Cep290-Mutant Mouse Model Of Severe Retinal Degeneration, Balajikarthick Subramanian, Manisha Anand, Hemant Khanna

UMass Center for Clinical and Translational Science Research Retreat

Purpose: Mutations in the CEP290 gene are a frequent cause of childhood blindness disorder, Leber congenital amaurosis (LCA). Not much is known about the mode of action of CEP290 in the retina. We previously showed that CEP290 interacts with RKIP and that RKIP protein is abnormally accumulated in rd16 (retinal degeneration 16) mouse, a model of Cep290- associated retinal degeneration. The purpose of this study is to evaluate the role of RKIP accumulation in mediating photoreceptor degeneration in the rd16 mouse.

Methods: rd16/rd16:Rkip ko/Rkip ko double homozygous knock out mice were generated by breeding rd16 and Rkip ...


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 ...


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 ...


Adipose Tissue Inflammation In Diabetic Versus Non-Diabetic Pregnancies, Tiffany A. Moore Simas, Raziel Rojas-Rodriguez, Jacqueline Tessa Draper, Aylin Sert, Maxwell Kruse, Crina Boeras, Brittany Rosenthal, Olga Gaelikman, So-Yun Min, Katherine G. Leung, Silvia Corvera May 2014

Adipose Tissue Inflammation In Diabetic Versus Non-Diabetic Pregnancies, Tiffany A. Moore Simas, Raziel Rojas-Rodriguez, Jacqueline Tessa Draper, Aylin Sert, Maxwell Kruse, Crina Boeras, Brittany Rosenthal, Olga Gaelikman, So-Yun Min, Katherine G. Leung, Silvia Corvera

UMass Center for Clinical and Translational Science Research Retreat

Objective: Beyond weight associated with fetus, placenta, amniotic fluid and increased blood volume, adipose tissue (AT) expansion is an accepted and expected component of pregnancy weight gain. Normal pregnancy is associated with relative insulin resistance (IR). In non-pregnant humans, AT expansion has been associated with IR and AT inflammation. However, it is not known whether AT expansion and IR in pregnancy are also associated with AT inflammation. This pilot study examined relationships between AT expansion and inflammation in control versus diabetic pregnancies.

Methods: Eligible subjects undergoing scheduled Cesarean delivery for obstetric indications were prospectively enrolled. Subjects provided demographic and anthropometric ...


Transdifferentiation Of Α- To Β-Cells Is Enhanced In Fstl3 Ko Mice, Alan Schneyer, Danielle Andrzejewski, Amy Burnside, Melissa Brown May 2014

Transdifferentiation Of Α- To Β-Cells Is Enhanced In Fstl3 Ko Mice, Alan Schneyer, Danielle Andrzejewski, Amy Burnside, Melissa Brown

UMass Center for Clinical and Translational Science Research Retreat

Both type 1 and type 2 diabetes involve loss of functional pancreatic B-cells which is driving research into potential replacement sources. Expansion of functional B-cell mass, such as through induction of B-cell neogenesis or through transdifferentiation of A-cells into functional B-cells represent appealing therapeutic solutions to restoring glucose control. To date, however, these processes have been induced through genetic manipulation or severe pancreatic injury. It remains to be determined whether transdifferentiation or neogenesis contribute to functional B-cell mass under normal physiological conditions and/or contribute to B-cell expansion and how these processes are regulated.

We have reported that inactivation of ...


Morning And Evening Oscillators Cooperate To Reset Circadian Behavior In Response To Light Input, Pallavi Lamba, Diana Wentworth, Patrick Emery, Yong Zhang May 2014

Morning And Evening Oscillators Cooperate To Reset Circadian Behavior In Response To Light Input, Pallavi Lamba, Diana Wentworth, Patrick Emery, Yong Zhang

GSBS Student Publications

Light is a crucial input for circadian clocks. In Drosophila, short light exposure can robustly shift the phase of circadian behavior. The model for this resetting posits that circadian photoreception is cell autonomous: CRYPTOCHROME senses light, binds to TIMELESS (TIM), and promotes its degradation, which is mediated by JETLAG (JET). However, it was recently proposed that interactions between circadian neurons are also required for phase resetting. We identify two groups of neurons critical for circadian photoreception: the morning (M) and the evening (E) oscillators. These neurons work synergistically to reset rhythmic behavior. JET promotes acute TIM degradation cell autonomously in ...