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2014

Cellular and Molecular Physiology

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Articles 1 - 28 of 28

Full-Text Articles in Cell Biology

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 ...


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 ...


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

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

Gyongyi Szabo

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 ...


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 ...


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 ...


A Rhog/Ilk/Elmo2/Rac1 Pathways Modulates Microtubule Stability, Bradley C. Jackson Sep 2014

A Rhog/Ilk/Elmo2/Rac1 Pathways Modulates Microtubule Stability, Bradley C. Jackson

Electronic Thesis and Dissertation Repository

Integrin-linked kinase (ILK) is a widely expressed scaffold protein important for cell adhesion, migration, and phagocytosis. ILK and its interacting partner, engulfment and cell motility protein 2 (ELMO2), may also modulate microtubule dynamics. Here, I show that sustained microtubule growth and acetylated tubulin levels are reduced in the absence of ILK and, conversely, that exogenous ILK exerts a stabilizing effect on microtubules. Further, exogenous ELMO2, ras homology growth related protein (RHOG) and ras-related C3 botulinum toxin substrate 1 (RAC1) stabilize microtubules in an ILK-dependent manner. Potential downstream effectors of the effect of ILK on microtubule stability include glycogen synthase kinase- ...


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 ...


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 ...


Tattletales And T-Bow Update 20140602mon, George Mcnamara Jun 2014

Tattletales And T-Bow Update 20140602mon, George Mcnamara

George McNamara

Tattletales and T-Bow Update 20140602Mon

http://0-works.bepress.com.library.simmons.edu/gmcnamara/42

Please see also http://0-works.bepress.com.library.simmons.edu/gmcnamara/26

Tattletales: multiplex fluorescent protein biosensors by spatial localization with TALE-FPs, Cas9-FPs, ZF-FPs, LacI-FPs, TetR-FPs, etc.

T-Bow: Rainbow T-cells and Tumor cells (and ES cells, iPS cells, other cells and organisms). You can think of this as "Brainbow meets TALENs/Cas9/ZFNs/other DNA sequence specific binding proteins".

If not familiar with Brainbow, see

http://en.wikipedia.org/wiki/Brainbow

If not familiar with TALENs, Cas9, etc, see

http://www.addgene.org/genome_engineering/

Big idea: localizing fluorescent proteins - and/or Nano-Lanterns ...


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 ...


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 ...


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 ...


The Role Of Integrins In Support Of Pancreatic Function, Survival And Maturation, Matthew Riopel May 2014

The Role Of Integrins In Support Of Pancreatic Function, Survival And Maturation, Matthew Riopel

Electronic Thesis and Dissertation Repository

The pancreas is a glandular organ composed of endocrine and exocrine compartments. Integrins are cell adhesion molecules that connect cells to the extracellular matrix (ECM). Integrins modulate a variety of cellular effects, yet their mechanism of action in the developed pancreas is not well understood. Fibrin is a provisional ECM protein that contains ligands for integrin receptors. Fibrin is capable of supporting islet health, but it is unclear how fibrin exerts its effects. The objective of this thesis is to understand the role of integrin receptors on in vivo pancreatic cell function, survival, and proliferation. In addition, this thesis investigates ...


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 ...


Pos-1 Regulation Of Endo-Mesoderm Identity In C. Elegans: A Dissertation, Ahmed M. Elewa Apr 2014

Pos-1 Regulation Of Endo-Mesoderm Identity In C. Elegans: A Dissertation, Ahmed M. Elewa

GSBS Dissertations and Theses

How do embryos develop with such poise from a single zygote to multiple cells with different identities, and yet survive? At the four-cell stage of the C. elegans embryo, only the blastomere EMS adopts the endo-mesoderm identity. This fate requires SKN-1, the master regulator of endoderm and mesoderm differentiation. However, in the absence of the RNA binding protein POS-1, EMS fails to fulfill its fate despite the presence of SKN-1. pos-1(-) embryos die gutless. Conversely, the RNA binding protein MEX-5 prevents ectoderm blastomeres from adopting the endo-mesoderm identity by repressing SKN-1. mex-5(-) embryos die with excess muscle at the expense ...


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 ...


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 ...


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 ...


The Ppargamma Locus Makes Long-Range Chromatin Interactions With Selected Tissue-Specific Gene Loci During Adipocyte Differentiation In A Protein Kinase A Dependent Manner, Scott E. Leblanc, Qiong Wu, A. Rasim Barutcu, Hengyi Xiao, Yasuyuki Ohkawa, Anthony N. Imbalzano Jan 2014

The Ppargamma Locus Makes Long-Range Chromatin Interactions With Selected Tissue-Specific Gene Loci During Adipocyte Differentiation In A Protein Kinase A Dependent Manner, Scott E. Leblanc, Qiong Wu, A. Rasim Barutcu, Hengyi Xiao, Yasuyuki Ohkawa, Anthony N. Imbalzano

Imbalzano Lab Publications

Differentiation signaling results in reprogramming of cellular gene expression that leads to morphological changes and functional specialization of a precursor cell. This global change in gene expression involves temporal regulation of differentiation-specific genes that are located throughout the genome, raising the idea that genome structure may also be re-organized during cell differentiation to facilitate regulated gene expression. Using in vitro adipocyte differentiation as a model, we explored whether gene organization within the nucleus is altered upon exposure of precursor cells to signaling molecules that induce adipogenesis. The peroxisome proliferator-activated receptor gamma (PPARgamma) nuclear hormone receptor is a master determinant of ...


Rapid Method Of Processing Sperm For Nucleic Acid Extraction In Clinical Research, Matthew K. De Gannes Jan 2014

Rapid Method Of Processing Sperm For Nucleic Acid Extraction In Clinical Research, Matthew K. De Gannes

Masters Theses

Background: Sperm contain highly compact nuclei, inhibiting DNA extraction using traditional techniques. Current methods extracting sperm DNA involve lengthy lysis and no means of stabilizing DNA, hindering clinical research.

Objective: We sought to optimize an efficient method of extracting high quality human sperm DNA.

Methods: Sperm from three volunteers were isolated using PureCeption. We tested 1) proteinase K with DNA/RNA Shield, 2) DTT and TCEP as reducing agents, 3) QIAshredder homogenization, and 4) stability of sperm DNA fresh (baseline) or after 4 weeks of storage at 4OC in DNA/RNA Shield using modified Quick-gDNA MiniPrep. DNA was ...