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Physiology

2013

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Articles 1 - 30 of 33

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

Prmt7 Is Dispensable In Tissue Culture Models For Adipogenic Differentiation, Yu-Jie Hu, Said Sif, Anthony N. Imbalzano Dec 2013

Prmt7 Is Dispensable In Tissue Culture Models For Adipogenic Differentiation, Yu-Jie Hu, Said Sif, Anthony N. Imbalzano

Imbalzano Lab Publications

Protein arginine methylation is a common posttranslational modification that has been implicated in numerous biological processes including gene expression. The mammalian genome encodes nine protein arginine methyltransferases (Prmts) that catalyze monomethylation, asymmetric dimethylation, and symmetric dimethylation on arginine residues. Protein arginine methyltransferase 7 (Prmt7) is categorized as a type II and type III enzyme that produces symmetric dimethylated arginine and monomethylated arginine, respectively. However, the biological role of Prmt7 is not well characterized. We previously showed that Prmt5, a type II Prmt that associates with Brg1-based SWI/SNF chromatin remodeling complex, is required for adipocyte differentiation. Since Prmt7 also associates ...


From Heart Beats To Health Recipes: The Role Of Fractal Physiology In The Ancestral Health Movement, Aaron P. Blaisdell, Brent Pottenger, John S. Torday Dec 2013

From Heart Beats To Health Recipes: The Role Of Fractal Physiology In The Ancestral Health Movement, Aaron P. Blaisdell, Brent Pottenger, John S. Torday

Journal of Evolution and Health

The human body—an amazing biological system that scales up fractally from its cellular building blocks—exhibits an incredible ability to self heal. Why then, are chronic diseases and degeneration on the rise in the population? Why are we sicker, more obese, and more depressed and stressed than ever before in human history? Why can’t we heal? The answers to these questions may lie in our ancestry, and modern departure from the human ecological niche. The ability to heal requires proper spatio-temporal inputs—nutrition, sleep, stress, activity, and socialization—in order for cellular signaling to occur properly across semi-permeable ...


Hdac6 Regulates Tip60-P400 Function In Stem Cells, Poshen B. Chen, Jui-Hung Hung, Taylor L. Hickman, Andrew H. Coles, James F. Carey, Zhiping Weng, Feixia Chu, Thomas G. Fazzio Dec 2013

Hdac6 Regulates Tip60-P400 Function In Stem Cells, Poshen B. Chen, Jui-Hung Hung, Taylor L. Hickman, Andrew H. Coles, James F. Carey, Zhiping Weng, Feixia Chu, Thomas G. Fazzio

Program in Molecular Medicine Publications and Presentations

In embryonic stem cells (ESCs), the Tip60 histone acetyltransferase activates genes required for proliferation and silences genes that promote differentiation. Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60-p400 complex from ESCs. Hdac6 is necessary for regulation of most Tip60-p400 target genes, particularly those repressed by the complex. Unlike differentiated cells, where Hdac6 is mainly cytoplasmic, Hdac6 is largely nuclear in ESCs, neural stem cells (NSCs), and some cancer cell lines, and interacts with Tip60-p400 in each. Hdac6 localizes to promoters bound by Tip60-p400 in ESCs, binding downstream of transcription start sites. Surprisingly, Hdac6 does not ...


Functional Overlap Among Distinct G1/S Inhibitory Pathways Allows Robust G1 Arrest By Yeast Mating Pheromones, Patricia A. Pope, Peter M. Pryciak Dec 2013

Functional Overlap Among Distinct G1/S Inhibitory Pathways Allows Robust G1 Arrest By Yeast Mating Pheromones, Patricia A. Pope, Peter M. Pryciak

GSBS Student Publications

In budding yeast, mating pheromones arrest the cell cycle in G1 phase via a pheromone-activated Cdk-inhibitor (CKI) protein, Far1. Alternate pathways must also exist, however, because deleting the cyclin CLN2 restores pheromone arrest to far1 cells. Here we probe whether these alternate pathways require the G1/S transcriptional repressors Whi5 and Stb1 or the CKI protein Sic1, whose metazoan analogues (Rb or p27) antagonize cell cycle entry. Removing Whi5 and Stb1 allows partial escape from G1 arrest in far1 cln2 cells, along with partial derepression of G1/S genes, which implies a repressor-independent route for inhibiting G1/S transcription. This ...


Diet-Induced Obesity Mediated By The Jnk/Dio2 Signal Transduction Pathway, Santiago Vernia, Julie Cavanagh-Kyros, Tamera Barrett, Dae Young Jung, Jason K. Kim, Roger J. Davis Nov 2013

Diet-Induced Obesity Mediated By The Jnk/Dio2 Signal Transduction Pathway, Santiago Vernia, Julie Cavanagh-Kyros, Tamera Barrett, Dae Young Jung, Jason K. Kim, Roger J. Davis

Program in Molecular Medicine Publications and Presentations

The cJun N-terminal kinase (JNK) signaling pathway is a key mediator of metabolic stress responses caused by consuming a high-fat diet, including the development of obesity. To test the role of JNK, we examined diet-induced obesity in mice with targeted ablation of Jnk genes in the anterior pituitary gland. These mice exhibited an increase in the pituitary expression of thyroid-stimulating hormone (TSH), an increase in the blood concentration of thyroid hormone (T4), increased energy expenditure, and markedly reduced obesity compared with control mice. The increased amount of pituitary TSH was caused by reduced expression of type 2 iodothyronine deiodinase (Dio2 ...


The Dna Damage And The Dna Replication Checkpoints Converge At The Mbf Transcription Factor, Tsvetomira Ivanova, Isabel Alves-Rodrigues, Blanca Gomez-Escoda, Chaitali Dutta, James A. Decaprio, Nicholas R. Rhind, Elena Hidalgo, Jose Ayte Nov 2013

The Dna Damage And The Dna Replication Checkpoints Converge At The Mbf Transcription Factor, Tsvetomira Ivanova, Isabel Alves-Rodrigues, Blanca Gomez-Escoda, Chaitali Dutta, James A. Decaprio, Nicholas R. Rhind, Elena Hidalgo, Jose Ayte

University of Massachusetts Medical School Faculty Publications

In fission yeast cells, Cds1 is the effector kinase of the DNA replication checkpoint. We previously showed that when the DNA replication checkpoint is activated, the repressor Yox1 is phosphorylated and inactivated by Cds1, resulting in activation of MluI-binding factor (MBF)-dependent transcription. This is essential to reinitiate DNA synthesis and for correct G1-to-S transition. Here we show that Cdc10, which is an essential part of the MBF core, is the target of the DNA damage checkpoint. When fission yeast cells are treated with DNA-damaging agents, Chk1 is activated and phosphorylates Cdc10 at its carboxy-terminal domain. This modification is responsible ...


Rage Is A Nucleic Acid Receptor That Promotes Inflammatory Responses To Dna, Cherilyn M. Sirois, Tengchuan Jin, Allison L. Miller, Damien Bertheloot, Hirotaka Nakamura, Gabor Horvath, Abubakar Mian, Jiansheng Jiang, Jacob Schrum, Lukas Bossaller, Karin Pelka, Natalio Garbi, Yambasu Brewah, Jane Tian, Chewshun Chang, Partha S. Chowdhury, Gary P. Sims, Roland Kolbeck, Anthony J. Coyle, Alison A. Humbles, T. Sam Xiao, Eicke Latz Oct 2013

Rage Is A Nucleic Acid Receptor That Promotes Inflammatory Responses To Dna, Cherilyn M. Sirois, Tengchuan Jin, Allison L. Miller, Damien Bertheloot, Hirotaka Nakamura, Gabor Horvath, Abubakar Mian, Jiansheng Jiang, Jacob Schrum, Lukas Bossaller, Karin Pelka, Natalio Garbi, Yambasu Brewah, Jane Tian, Chewshun Chang, Partha S. Chowdhury, Gary P. Sims, Roland Kolbeck, Anthony J. Coyle, Alison A. Humbles, T. Sam Xiao, Eicke Latz

University of Massachusetts Medical School Faculty Publications

Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products (RAGE) promoted DNA uptake into endosomes and lowered the immune recognition threshold for the activation of Toll-like receptor 9, the principal DNA-recognizing transmembrane signaling receptor. Structural analysis ...


Analysis Of In Vitro Insulin-Resistance Models And Their Physiological Relevance To In Vivo Diet-Induced Adipose Insulin Resistance, Kinyui Alice Lo, Adam Labadorf, Norman J. Kennedy, Myoung Souk Han, Yoon Sing Yap, Bryan Matthews, Xiaofeng Xin, Lei Sun, Roger J. Davis, Harvey F. Lodish, Ernest Fraenkel Oct 2013

Analysis Of In Vitro Insulin-Resistance Models And Their Physiological Relevance To In Vivo Diet-Induced Adipose Insulin Resistance, Kinyui Alice Lo, Adam Labadorf, Norman J. Kennedy, Myoung Souk Han, Yoon Sing Yap, Bryan Matthews, Xiaofeng Xin, Lei Sun, Roger J. Davis, Harvey F. Lodish, Ernest Fraenkel

Davis Lab Publications

Diet-induced obesity (DIO) predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but what aspects of the in vivo responses are captured by these models remains unknown. We use global RNA sequencing to investigate changes induced by TNF-alpha, hypoxia, dexamethasone, high insulin, and a combination of TNF-alpha and hypoxia, comparing the results to the changes in white adipose tissue from DIO mice. We found that different in vitro models capture distinct features of DIO adipose insulin resistance, and a combined treatment ...


Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass Oct 2013

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Aaron P Blaisdell

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.


Functional Activity Of Rlim/Rnf12 Is Regulated By Phosphorylation-Dependent Nucleo-Cytoplasmic Shuttling, Baowei Jiao, Naoko Taniguchi-Ishigaki, Cenap Gungor, Marvin A. Peters, Ya-Wen Chen, Sabine Riethdorf, Alexander Drung, Leanne G. Ahronian, Jongdae Shin, Rachna Pagnis, Klaus Pantel, Taro Tachibana, Brian C. Lewis, Steven A. Johnsen, Ingolf Bach Oct 2013

Functional Activity Of Rlim/Rnf12 Is Regulated By Phosphorylation-Dependent Nucleo-Cytoplasmic Shuttling, Baowei Jiao, Naoko Taniguchi-Ishigaki, Cenap Gungor, Marvin A. Peters, Ya-Wen Chen, Sabine Riethdorf, Alexander Drung, Leanne G. Ahronian, Jongdae Shin, Rachna Pagnis, Klaus Pantel, Taro Tachibana, Brian C. Lewis, Steven A. Johnsen, Ingolf Bach

Program in Gene Function and Expression Publications and Presentations

The X-linked gene Rnf12 encodes the ubiquitin ligase RLIM/Rnf12 which serves as a major sex-specific epigenetic regulator of female mouse nurturing tissues. Early during embryogenesis, RLIM/Rnf12 expressed from the maternal allele is crucial for the development of extraembryonic trophoblast cells. In contrast, in mammary glands of pregnant and lactating adult females RLIM/Rnf12 expressed from the paternal allele functions as a critical survival factor for milk producing alveolar cells. While RLIM/Rnf12 is detected mostly in the nucleus, little is known about how and in which cellular compartment(s) RLIM/Rnf12 mediates its biological functions. Here, we demonstrate ...


Inductive Asymmetric Cell Division: The Wrm Leads The Way, Takao Ishidate, Soyoung Kim, Craig C. Mello, Masaki Shirayama Oct 2013

Inductive Asymmetric Cell Division: The Wrm Leads The Way, Takao Ishidate, Soyoung Kim, Craig C. Mello, Masaki Shirayama

Program in Molecular Medicine Publications and Presentations

C. elegans, with its invariant cell lineage, provides a powerful model system in which to study signaling-dependent asymmetric cell division. The C. elegans β-catenin-related protein, WRM-1, specifies endoderm at the 4-cell stage during the first cell signaling-induced asymmetric cell division of embryogenesis. During this interaction, Wnt signaling and the cell cycle regulator CDK-1 act together to induce the asymmetric cortical release of WRM-1 at prophase of the EMS cell cycle. Genetic studies suggest that release of WRM-1 unmasks a cortical site that drives EMS spindle rotation onto the polarized axis of the cell, simultaneously making WRM-1 available for nuclear translocation ...


Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass Sep 2013

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Journal of Evolution and Health

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.


Computational Optogenetics: Empirically-Derived Voltage- And Light-Sensitive Channelrhodopsin-2 Model, John C. Williams, Jianjin Xu, Zhongju Lu, Aleksandra Klimas, Xuxin Chen, Christina M. Ambrosi, Ira S. Cohen, Emilia Entcheva Sep 2013

Computational Optogenetics: Empirically-Derived Voltage- And Light-Sensitive Channelrhodopsin-2 Model, John C. Williams, Jianjin Xu, Zhongju Lu, Aleksandra Klimas, Xuxin Chen, Christina M. Ambrosi, Ira S. Cohen, Emilia Entcheva

Department of Biomedical Engineering Faculty Publications

Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology. An accurate quantitative model of ChR2 is necessary for in silicoprediction of the response to optical stimulation in realistic tissue/organ settings. Such a model can guide the rational design of new ion channel functionality tailored to different cell types/tissues. Focusing on one of the most widely used ChR2 mutants (H134R) with enhanced current, we collected a comprehensive experimental data set of the response of this ion channel to different irradiances ...


Brg1, A Swi/Snf Chromatin Remodeling Enzyme Atpase, Is Required For Maintenance Of Nuclear Shape And Integrity, Anthony N. Imbalzano, Karen M. Imbalzano, Jeffrey A. Nickerson Sep 2013

Brg1, A Swi/Snf Chromatin Remodeling Enzyme Atpase, Is Required For Maintenance Of Nuclear Shape And Integrity, Anthony N. Imbalzano, Karen M. Imbalzano, Jeffrey A. Nickerson

Imbalzano Lab Publications

We recently reported that reducing the levels of BRG1, the catalytic subunit of mammalian SWI/SNF chromatin remodeling enzymes, induces alterations in nuclear shape in a breast epithelial cell line. Immunostaining the BRG1 knockdown cells with nuclear lamina antibodies revealed a significantly increased frequency of grooves, or invaginations, in the nuclei. Disruption of each of the major cytoplasmic filament systems (actin, tubulin and cytokeratins) had no impact on the BRG1-dependent changes in nuclear shape, indicating that the observed changes in nuclear morphology are unlikely to be a result of alterations in the integrity of the nuclear-cytoplamic contacts in the cell ...


Role Of The Mixed-Lineage Protein Kinase Pathway In The Metabolic Stress Response To Obesity, Shashi Kant, Tamera Barrett, Anastassiia Vertii, Yun Hee Noh, Dae Young Jung, Jason K. Kim, Roger J. Davis Aug 2013

Role Of The Mixed-Lineage Protein Kinase Pathway In The Metabolic Stress Response To Obesity, Shashi Kant, Tamera Barrett, Anastassiia Vertii, Yun Hee Noh, Dae Young Jung, Jason K. Kim, Roger J. Davis

Program in Molecular Medicine Publications and Presentations

Saturated free fatty acid (FFA) is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK) pathway that activates cJun NH2-terminal kinase (JNK). Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that lack expression of MLK2 and MLK3. MLK deficiency protected mice against high-fat-diet-induced insulin resistance and obesity. Reduced JNK activation and increased energy expenditure contribute to ...


Physiologically-Based Pharmacokinetic Modeling For Predicting Caffeine/Theophylline-Ciprofloxacin Interactions, David M. Ng, Ali Navid Aug 2013

Physiologically-Based Pharmacokinetic Modeling For Predicting Caffeine/Theophylline-Ciprofloxacin Interactions, David M. Ng, Ali Navid

STAR (STEM Teacher and Researcher) Presentations

Dynamics of interactions between the drugs caffeine, theophylline, and ciprofloxacin are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drugs are distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body are reflected in the structure and functioning of the model. Multiple drugs can interact to increase or decrease their beneficial and/or undesired effects. This is important because some common substances, such as caffeine in coffee, soft drinks, and energy drinks, are actually drugs that affect the body. Ciprofloxacin is an inhibitor of caffeine and theophylline metabolism; such ...


Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi Jul 2013

Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi

Electronic Thesis and Dissertation Repository

Clinical studies have demonstrated that intrauterine growth restriction (IUGR) offspring, faced with a nutritional mismatch postpartum, have an increased risk of developing the metabolic syndrome. The maternal protein restriction (MPR) rat model has been extensively studied to investigate the adverse effects of a nutritional mismatch in postnatal life of IUGR offspring. Previous studies have demonstrated that MPR leads to impaired function of the liver, an important metabolic organ. However the underlying mechanisms which predispose these offspring to the metabolic syndrome remain elusive. In the following studies, low protein diet during pregnancy and lactation led to IUGR offspring with decreased liver ...


Jnk Regulates Compliance-Induced Adherens Junctions Formation In Epithelial Cells And Tissues, Hui You, Roshan M. Padmashali, Aishwarya Ranganathan, Pedro Lei, Nomeda Girnius, Roger J. Davis, Stelios T. Andreadis Jun 2013

Jnk Regulates Compliance-Induced Adherens Junctions Formation In Epithelial Cells And Tissues, Hui You, Roshan M. Padmashali, Aishwarya Ranganathan, Pedro Lei, Nomeda Girnius, Roger J. Davis, Stelios T. Andreadis

Davis Lab Publications

We demonstrate that c-Jun N-terminal kinase (JNK) responds to substrate stiffness and regulates adherens junction (AJ) formation in epithelial cells in 2D cultures and in 3D tissues in vitro and in vivo. Rigid substrates led to JNK activation and AJ disassembly, whereas soft matrices suppressed JNK activity leading to AJ formation. Expression of constitutively active JNK (MKK7-JNK1) induced AJ dissolution even on soft substrates, whereas JNK knockdown (using shJNK) induced AJ formation even on hard substrates. In human epidermis, basal cells expressed phosphorylated JNK but lacked AJ, whereas suprabasal keratinocytes contained strong AJ but lacked phosphorylated JNK. AJ formation was ...


Phosphorylation Of Centromeric Histone H3 Variant Regulates Chromosome Segregation In S. Cerevisiae, Lars Boeckmann, Yoshimitsu Takahashi, Wei-Chun Au, Prashant K. Mishra, John S. Choy, Anthony R. Dawson, May Y. Szeto, Timothy J. Waybright, Christopher Heger, Christopher Mcandrew, Paul K. Goldsmith, Timothy D. Veenstra, Richard E. Baker, Munira A. Basrai Jun 2013

Phosphorylation Of Centromeric Histone H3 Variant Regulates Chromosome Segregation In S. Cerevisiae, Lars Boeckmann, Yoshimitsu Takahashi, Wei-Chun Au, Prashant K. Mishra, John S. Choy, Anthony R. Dawson, May Y. Szeto, Timothy J. Waybright, Christopher Heger, Christopher Mcandrew, Paul K. Goldsmith, Timothy D. Veenstra, Richard E. Baker, Munira A. Basrai

University of Massachusetts Medical School Faculty Publications

The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We have identified posttranslational modifications of S. cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants showed growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody we showed that the association of phosphorylated Cse4 with centromeres is increased in response to defective microtubule attachment or reduced cohesion. We determined that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 were reduced at centromeres in ipl1 strains in vivo and in vitro assays showed ...


Investigation Of Multiple Concerted Mechanisms Underlying Stimulus-Induced G1 Arrest In Yeast: A Dissertation, Patricia A. Pope Jun 2013

Investigation Of Multiple Concerted Mechanisms Underlying Stimulus-Induced G1 Arrest In Yeast: A Dissertation, Patricia A. Pope

GSBS Dissertations and Theses

Progression through the cell cycle is tightly controlled, and the decision whether or not to enter a new cell cycle can be influenced by both internal and external cues. For budding yeast one such external cue is pheromone treatment, which can induce G1 arrest. Two distinct mechanisms are known to be involved in this arrest, one dependent on the arrest protein Far1 and one independent of Far1, but the exact mechanisms have remained enigmatic. The studies presented here further elucidate both of these mechanisms.

We looked at two distinct aspects of the Far1-independent arrest mechanism. First, we studied the role ...


Validation Of Antibodies Used To Study Hypoxia Inducible Factors In Two Species Of Fundulus, Jenna D. Hill May 2013

Validation Of Antibodies Used To Study Hypoxia Inducible Factors In Two Species Of Fundulus, Jenna D. Hill

University of New Orleans Theses and Dissertations

Hypoxia inducible factors (HIFs) are transcription factors and the master regulators of oxygen-dependent gene expression in animals. The focus of this thesis is the distribution of HIF protein in tissues of the fish Fundulus heteroclitus and F. grandis, two widespread species that occur in naturally hypoxic waters. Polyclonal antibodies against HIF-1α, HIF-2α, and HIF-3α were tested on proteins made in vitro and on extracts made from several tissues of normoxic and hypoxic fish. Antibodies against HIF-1α and 3α bound specifically to full length protein made in vitro, and produced bands on western blots of nuclear extracts of near the expected ...


Pathogenesis Of Atherosclerosis: Focusing On The Role Of Exercise And Flavonoids, Mahdi Garelnabi, Halleh Mahini May 2013

Pathogenesis Of Atherosclerosis: Focusing On The Role Of Exercise And Flavonoids, Mahdi Garelnabi, Halleh Mahini

UMass Center for Clinical and Translational Science Research Retreat

Atherosclerotic coronary artery disease accounts for the majority of death in the world. A number of determinants most of them associated with lifestyle starting from early childhood onwards are responsible for Cardiovascular Diseases (CVD). Some risk factors facilitate the development of atherosclerosis, while others participate in the plaques formation, resulting in the manifestation of the disease.

Objectives: In the current study we investigated the role of exercise and antioxidants intakes; specifically quercetin in mouse model. We looked into the sex responses to the quercetin intake and physical activity. We also looked into the effect of quercetin treatment on HepG2 cell ...


From Gibbons To Gymnasts: A Look At The Biomechanics And Neurophysiology Of Brachiation In Gibbons And Its Human Rediscovery, Emma Et Pennock May 2013

From Gibbons To Gymnasts: A Look At The Biomechanics And Neurophysiology Of Brachiation In Gibbons And Its Human Rediscovery, Emma Et Pennock

Student Works

This conference paper serves to examine the evolutionary linkages of a brachiating ancestor in humans, the biomechanical and neurophysiology of modern day brachiators, and the human rediscovery of this form of locomotion. Brachiation is arguably one of the most metabolically effective modes of travel by any organism and can be observed most meritoriously in Gibbons. The purpose of the research conducted for this paper was to encourage further exploration of the neurophysiological similarities and differences between humans and non-human primates. The hope is that in spurring more interest and research in this area, further possibilities for rehabilitating brain injury will ...


Enabling Sum Frequency Spectroscopy And Fluorescence Correlation Spectroscopy Of Model Cellular Membranes, Sarah M. Sterling May 2013

Enabling Sum Frequency Spectroscopy And Fluorescence Correlation Spectroscopy Of Model Cellular Membranes, Sarah M. Sterling

Electronic Theses and Dissertations

The majority of proteins secreted from cells contain a signal peptide sequence that is required for secretion mediated by the endoplasmic reticulum and Golgi apparatus. However, many proteins lack the essential signal peptide sequence, yet still undergo secretion. Such proteins are known to regulate cell proliferation, differentiation, and migration. Fibroblast growth factor 1 (FGF-1) is one protein which undergoes non-classical protein transport. The role of its interactions with the cellular membrane during non-classical protein transport is not fully understood, although FGF-1 has shown preferential destabilizing effects on artificial membranes composed of acidic phospholipids. In the present work, physiologically relevant model ...


Nuclear Localization Of Cpi-17, A Protein Phosphatase-1 Inhibitor Protein, Affects Histone H3 Phosphorylation And Corresponds To Proliferation Of Cancer And Smooth Muscle Cells., Masumi Eto, Jason A Kirkbride, Rishika Chugh, Nana Kofi Karikari, Jee In Kim Apr 2013

Nuclear Localization Of Cpi-17, A Protein Phosphatase-1 Inhibitor Protein, Affects Histone H3 Phosphorylation And Corresponds To Proliferation Of Cancer And Smooth Muscle Cells., Masumi Eto, Jason A Kirkbride, Rishika Chugh, Nana Kofi Karikari, Jee In Kim

Department of Molecular Physiology and Biophysics Faculty Papers

CPI-17 (C-kinase-activated protein phosphatase-1 (PP1) inhibitor, 17kDa) is a cytoplasmic protein predominantly expressed in mature smooth muscle (SM) that regulates the myosin-associated PP1 holoenzyme (MLCP). Here, we show CPI-17 expression in proliferating cells, such as pancreatic cancer and hyperplastic SM cells. Immunofluorescence showed that CPI-17 was concentrated in nuclei of human pancreatic cancer (Panc1) cells. Nuclear accumulation of CPI-17 was also detected in the proliferating vascular SM cell culture and cells at neointima of rat vascular injury model. The N-terminal 21-residue tail domain of CPI-17 was necessary for the nuclear localization. Phospho-mimetic Asp-substitution of CPI-17 at Ser12 attenuated the nuclear ...


Genetic Deficiency Of Cd40 In Mice Exacerbates Metabolic Manifestations Of Diet-Induced Obesity: A Dissertation, Chang-An Guo Apr 2013

Genetic Deficiency Of Cd40 In Mice Exacerbates Metabolic Manifestations Of Diet-Induced Obesity: A Dissertation, Chang-An Guo

GSBS Dissertations and Theses

The past two decades have seen an explosive increase of obesity rates worldwide, with more than one billion adults overweight and 300 million of them obese. Obesity and its associated complications have become leading causes of morbidity and mortality in the United States and major contributing factors to the rising costs of national health care.

The pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation and chronic activation of immune pathways in adipose tissue and liver. The CD40 receptor and its ligand, CD40L, initiate immune cell signaling promoting inflammation, but conflicting data on ...


Elongation Factor 1a-1 And Hepatocyte Response To Fatty Acid Excess, Alexandra M. Stoianov Apr 2013

Elongation Factor 1a-1 And Hepatocyte Response To Fatty Acid Excess, Alexandra M. Stoianov

Electronic Thesis and Dissertation Repository

Obesity is associated with elevated levels of serum fatty acids, which accumulate in nonadipose tissues including the liver. Elongation factor 1A-1 (EF1A-1) has previously been shown to participate in the cell stress and death response of cardiomyocytes to excess saturated fatty exposure, and in steatotic mouse myocardium. In this thesis, the hypothesis that the hepatocyte response to fatty acid overload involves EF1A-1 was tested. EF1A-1 expression was induced in the livers of obese mice in association with severe hepatic steatosis, and in HepG2 human hepatoma cells in response to excess palmitate. Partial translocation of EF1A-1 from the ER to polymerized ...


Crosstalk Between Casein Kinase Ii And Ste20-Related Kinase Nak1, Lubos Cipak, Sneha Gupta, Iva Rajovic, Quan-Wen Jin, Dorothea Anrather, Gustav Ammerer, Dannel Mccollum, Juraj Gregan Mar 2013

Crosstalk Between Casein Kinase Ii And Ste20-Related Kinase Nak1, Lubos Cipak, Sneha Gupta, Iva Rajovic, Quan-Wen Jin, Dorothea Anrather, Gustav Ammerer, Dannel Mccollum, Juraj Gregan

GSBS Student Publications

Although the sterile 20 (Ste20) serine/threonine protein kinase was originally identified as a component of the S. cerevisiae mating pathway, it has homologs in higher eukaryotes and is part of a larger family of Ste20-like kinases. Ste20-like kinases are involved in multiple cellular processes, such as cell growth, morphogenesis, apoptosis and immune response. Carrying out such a diverse array of biological functions requires numerous regulatory inputs and outputs in the form of protein-protein interactions and post-translational modifications. Hence, a thorough knowledge of Ste20-like kinase binding partners and phosphorylation sites will be essential for understanding the various roles of these ...


The Cellular And Molecular Basis Of Bitter Tastant-Induced Bronchodilation, Cheng-Hai Zhang, Lawrence M. Lifshitz, Karl Uy, Mitsuo Ikebe, Kevin E. Fogarty, Ronghua Zhuge Mar 2013

The Cellular And Molecular Basis Of Bitter Tastant-Induced Bronchodilation, Cheng-Hai Zhang, Lawrence M. Lifshitz, Karl Uy, Mitsuo Ikebe, Kevin E. Fogarty, Ronghua Zhuge

University of Massachusetts Medical School Faculty Publications

Bronchodilators are a standard medicine for treating airway obstructive diseases, and beta2 adrenergic receptor agonists have been the most commonly used bronchodilators since their discovery. Strikingly, activation of G-protein-coupled bitter taste receptors (TAS2Rs) in airway smooth muscle (ASM) causes a stronger bronchodilation in vitro and in vivo than beta2 agonists, implying that new and better bronchodilators could be developed. A critical step towards realizing this potential is to understand the mechanisms underlying this bronchodilation, which remain ill-defined. An influential hypothesis argues that bitter tastants generate localized Ca(2+) signals, as revealed in cultured ASM cells, to activate large-conductance Ca(2 ...


Uv Damage Regulates Alternative Polyadenylation Of The Rpb2 Gene In Yeast, Lijian Yu, Michael R. Volkert Mar 2013

Uv Damage Regulates Alternative Polyadenylation Of The Rpb2 Gene In Yeast, Lijian Yu, Michael R. Volkert

University of Massachusetts Medical School Faculty Publications

Alternative polyadenylation (APA) is conserved in all eukaryotic cells. Selective use of polyadenylation sites appears to be a highly regulated process and contributes to human pathogenesis. In this article we report that the yeast RPB2 gene is alternatively polyadenylated, producing two mRNAs with different lengths of 3'UTR. In normally growing wild-type cells, polyadenylation preferentially uses the promoter-proximal poly(A) site. After UV damage transcription of RPB2 is initially inhibited. As transcription recovers, the promoter-distal poly(A) site is preferentially used instead, producing more of a longer form of RPB2 mRNA. We show that the relative increase in the long ...