Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, 2018 University of Massachusetts Medical School
Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, Adilson L. Guilherme, David J. Pedersen, Felipe Henriques, Alexander H. Bedard, Elizabeth Henchey, Mark Kelly, Kamal Rahmouni, Donald A. Morgan, Michael P. Czech
University of Massachusetts Medical School Faculty Publications
White adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of beige adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In ...
Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, 2018 University of Nebraska Medical Center
Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, Michael Price
Theses & Dissertations
Alcohol abuse, which can impair clearance of pathogens and debris from the airway, is associated with an increase in complications and a higher mortality rate during the progression of pneumonia. With prolonged alcohol exposure, mucociliary clearance (MCC), which depends on the coordinated beating of cilia, is dysfunctional. Effective MCC relies on cAMP-dependent protein kinase (PKA) activation of ciliary beat frequency (CBF). PKA activation and stimulation of CBF are blunted with chronic exposure to alcohol. This phenomenon is known as alcohol-induced ciliary dysfunction (AICD). Previous studies have shown that concomitant feeding of mice with alcohol and antioxidants prevents AICD, suggesting a ...
Pkm2 Influences The Metabolic Fate Of Butyrate In Colorectal Cancer Cells, 2018 University of Tennessee, Knoxville
Pkm2 Influences The Metabolic Fate Of Butyrate In Colorectal Cancer Cells, Megan Louise Pence
University of Tennessee Honors Thesis Projects
No abstract provided.
Efficient Blue To Red Afterglow Tuning In A Binary Nanocomposite Plastic Film, 2018 Jinan University - China
Efficient Blue To Red Afterglow Tuning In A Binary Nanocomposite Plastic Film, Yan Xia, Huase Ou, Wanbin Li, Gang Han, Zhanjun Li
Open Access Articles
Colorful spectra are important for the diverse applications of persistent phosphors. A color conversion concept is developed to obtain abundant persistent luminescence color by mining capacities of known persistent phosphors with the most efficient persistent properties. Here, SiO(2)/Sr(2)MgSi(2)O(7):Eu,Dy nanoparticles are chosen as a blue persistent luminescence donor nanophosphor, while ultrafine CaAlSiN(3):Eu is utilized as a red conversion phosphor to tune the persistent luminescence spectra from blue to red. The red afterglow emission can persist for more than 5 h. The decay of the red afterglow follows nearly the same ...
Effects Of Larval Density On Gene Regulation In Caenorhabditis Elegans During Routine L1 Synchronization, 2018 University of Massachusetts Medical School
Effects Of Larval Density On Gene Regulation In Caenorhabditis Elegans During Routine L1 Synchronization, Io Long Chan, Oliver J. Rando, Colin C. Conine
University of Massachusetts Medical School Faculty Publications
Bleaching gravid C. elegans followed by a short period of starvation of the L1 larvae is a routine method performed by worm researchers for generating synchronous populations for experiments. During the process of investigating dietary effects on gene regulation in L1 stage worms by single-worm RNA-Seq, we found that the density of resuspended L1 larvae affects expression of many mRNAs. Specifically, a number of genes related to metabolism and signalling are highly expressed in worms arrested at low density, but are repressed at higher arrest densities. We generated a GFP reporter strain based on one of the most density-dependent genes ...
N-Terminal Sumoylation Of Centromeric Histone H3 Variant Cse4 Regulates Its Proteolysis To Prevent Mislocalization To Non-Centromeric Chromatin, Kentaro Ohkuni, Reuben Levy-Myers, Jack Warren, Wei-Chun Au, Yoshimitsu Takahashi, Richard E. Baker, Munira A. Basrai
Open Access Articles
Stringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4. In this study, we have identified lysine 65 (K65) in Cse4 as a site that regulates sumoylation and ...
A Parental Requirement For Dual-Specificity Phosphatase 6 In Zebrafish, 2018 University of Massachusetts Medical School
A Parental Requirement For Dual-Specificity Phosphatase 6 In Zebrafish, Jennifer M. Maurer, Charles G. Sagerstrom
Open Access Articles
BACKGROUND: Signaling cascades, such as the extracellular signal-regulated kinase (ERK) pathway, play vital roles in early vertebrate development. Signals through these pathways are initiated by a growth factor or hormone, are transduced through a kinase cascade, and result in the expression of specific downstream genes that promote cellular proliferation, growth, or differentiation. Tight regulation of these signals is provided by positive or negative modulators at varying levels in the pathway, and is required for proper development and function. Two members of the dual-specificity phosphatase (Dusp) family, dusp6 and dusp2, are believed to be negative regulators of the ERK pathway and ...
Cbx4 Sumoylates Prdm16 To Regulate Adipose Tissue Thermogenesis, 2018 University of Massachusetts Medical School
Cbx4 Sumoylates Prdm16 To Regulate Adipose Tissue Thermogenesis, Qingbo Chen, Lei Huang, Dongning Pan, Lihua (Julie) Zhu, Yong-Xu Wang
Open Access Articles
Transcriptional co-activator Prdm16 controls brown fat development and white fat browning, but how this thermogenic function is modulated post-translationally is poorly understood. Here, we report that Cbx4, a Polycomb group protein, is a SUMO E3 ligase for Prdm16 and that Cbx4-mediated sumoylation of Prdm16 is required for thermogenic gene expression. Cbx4 expression is enriched in brown fat and is induced in adipose tissue by acute cold exposure. Sumoylation of Prdm16 at lysine 917 by Cbx4 blocks its ubiquitination-mediated degradation, thereby augmenting its stability and thermogenic function. Moreover, this sumoylation event primes Prdm16 to be further stabilized by methyltransferase Ehmt1. Heterozygous ...
C9orf72 Ggggcc Repeat-Associated Non-Aug Translation Is Upregulated By Stress Through Eif2alpha Phosphorylation, 2018 Johns Hopkins University
C9orf72 Ggggcc Repeat-Associated Non-Aug Translation Is Upregulated By Stress Through Eif2alpha Phosphorylation, Weiwei Cheng, Shaopeng Wang, Alexander A. Mestre, Chenglai Fu, Andres Makarem, Fengfan Xian, Lindsey R. Hayes, Rodrigo Lopez-Gonzalez, Kevin Drenner, Jie Jiang, Don W. Cleveland, Shuying Sun
Open Access Articles
Hexanucleotide repeat expansion in C9ORF72 is the most frequent cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we demonstrate that the repeat-associated non-AUG (RAN) translation of (GGGGCC) n -containing RNAs into poly-dipeptides can initiate in vivo without a 5'-cap. The primary RNA substrate for RAN translation of C9ORF72 sense repeats is shown to be the spliced first intron, following its excision from the initial pre-mRNA and transport to the cytoplasm. Cap-independent RAN translation is shown to be upregulated by various stress stimuli through phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF2alpha), the core ...
Marijuana And The Teenage Brain: Public Health Impact, 2018 University of Vermont
Marijuana And The Teenage Brain: Public Health Impact, Katie C. Warther
Family Medicine Clerkship Student Projects
This project explores the neurobiological impact of teenage marijuana use, and the ways that public health interventions can help educate adolescents and delay the onset of use.
Body Composition Vs Athletic Performance In Volleyball, 2018 The University of Akron
Body Composition Vs Athletic Performance In Volleyball, Elizabeth Decaro
Honors Research Projects
Objectives: The goal of this study was to determine if body composition affected athletic performance in the sport of volleyball at the University of Akron.
Methods: The study was conducted in the School of Sports Science & Wellness Education on the 3rd floor of Infocision Stadium at the University of Akron using the computer containing the Bod Pod data for the women’s volleyball team.
Results: 20 subjects of the women’s varsity volleyball team were studied. The averages of each test were varied between the different skills tests in counter-movement vertical jump, approach vertical jump, block, broad jump, chin-ups ...
Thermophilic Adaptation In Prokaryotes Is Constrained By Metabolic Costs Of Proteostasis, 2018 University of Massachusetts Medical School
Thermophilic Adaptation In Prokaryotes Is Constrained By Metabolic Costs Of Proteostasis, Sergey V. Venev, Konstantin B. Zeldovich
Open Access Articles
Prokaryotes evolved to thrive in an extremely diverse set of habitats, and their proteomes bear signatures of environmental conditions. Although correlations between amino acid usage and environmental temperature are well-documented, understanding of the mechanisms of thermal adaptation remains incomplete. Here, we couple the energetic costs of protein folding and protein homeostasis to build a microscopic model explaining both the overall amino acid composition and its temperature trends. Low biosynthesis costs lead to low diversity of physical interactions between amino acid residues, which in turn makes proteins less stable and drives up chaperone activity to maintain appropriate levels of folded, functional ...
Metabolic Dysregulation And Cancer Mortality In A National Cohort Of Blacks And Whites, 2017 University of Kentucky
Metabolic Dysregulation And Cancer Mortality In A National Cohort Of Blacks And Whites, Tomi Akinyemiju, Justin Xavier Moore, Suzanne Judd, Susan Lakoski, Michael Goodman, Monika M. Safford, Maria Pisu
Epidemiology Faculty Publications
Background: We examined the association between metabolic dysregulation and cancer mortality in a prospective cohort of Black and White adults.
Methods: A total of 25,038 Black and White adults were included in the analysis. Metabolic dysregulation was defined in two ways: 1) using the joint harmonized criteria for metabolic syndrome (MetS) and 2) based on factor analysis of 15 variables characterizing metabolic dysregulation. We estimated hazards ratios (HRs) and 95% confidence intervals (CIs) for the association of MetS and metabolic dysregulation with cancer mortality during follow-up using Cox proportional hazards models.
Results: About 46% of Black and 39% of ...
Nmd Monitors Translational Fidelity 24/7, 2017 University of Massachusetts Medical School
Nmd Monitors Translational Fidelity 24/7, Alper Celik, Feng He, Allan Jacobson
Open Access Articles
Nonsense-mediated mRNA decay (NMD) is generally thought to be a eukaryotic mRNA surveillance pathway tasked with the elimination of transcripts harboring an in-frame premature termination codon (PTC). As presently conceived, NMD acting in this manner minimizes the likelihood that potentially toxic polypeptide fragments would accumulate in the cytoplasm. This notion is to be contrasted to the results of systematic RNA-Seq and microarray analyses of NMD substrates in multiple model systems, two different experimental approaches which have shown that many mRNAs identified as NMD substrates fail to contain a PTC. Our recent results provide insight into, as well as a possible ...
Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel
Biochemistry -- Faculty Publications
Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.
Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.
Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation ...
Inhibition Of Cholesterol Biosynthesis Through Rnf145-Dependent Ubiquitination Of Scap, 2017 University of California - Los Angeles
Inhibition Of Cholesterol Biosynthesis Through Rnf145-Dependent Ubiquitination Of Scap, Li Zhang, Prashant Rajbhandari, Christina Priest, Jaspreet Sandhu, Xiaohui Wu, Ryan E. Temel, Antonio Castrillo, Thomas Q. De Aguiar Vallim, Tamer Sallam, Peter Tontonoz
Saha Cardiovascular Research Center Faculty Publications
Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show ...
Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, 2017 University of Kentucky
Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin
Sanders-Brown Center on Aging Faculty Publications
Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes ...
Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, 2017 University of Massachusetts Medical School
Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, Markus Parzival Vallaster
GSBS Dissertations and Theses
Environmental conditions imposed onto organisms during certain phases of their life cycles such as embryogenesis or puberty can not only impact the organisms’ own health, but also affect subsequent generations. The underlying mechanisms causing intergenerational phenotypes are not encoded in the genome, but the result of reversible epigenetic modifications. This work investigates in a mouse model the impact of paternal nicotine exposure on the next generation regarding addictive behavior modulation, metabolic changes, and molecular mechanisms. It provides evidence that male offspring from nicotine-exposed fathers (NIC offspring) is more resistant to lethal doses of nicotine. This phenotype is gender-specific and depends ...
Regulation Of Iron-Related Molecules In The Rat Hippocampus: Sex- And Age-Associated Differences, 2017 Marshall University
Regulation Of Iron-Related Molecules In The Rat Hippocampus: Sex- And Age-Associated Differences, Srinivasarao Thulluri, Miaozong Wu, Eric R. Blough, Nandini D.P.K. Manne, Ashley B. Litchfield, Bin Wang
Iron accumulation, especially that of free oxidized ferrous iron, has been shown to induce tissue oxidative damage and contribute to brain aging and the development of neurodegenerative disease. Here we examine whether sex and advanced age affect the expression of iron-related molecules that participate in regulating free iron levels (heme oxygenase I (HOI), iron-regulatory protein I (IRPI), and ferritin heavy chain (FTH)) and whether changes in the expression of these molecules are associated with differences in the expression of alpha-synuclein (ASN) which is thought to be a critical regulator in the pathogenesis of neurodegeneration. Using a well-established aging animal model ...
Autophagy And Protein Turnover Responses To Exercise-Nutrient Interactions In Human Skeletal Muscle, 2017 Australian Catholic University
Autophagy And Protein Turnover Responses To Exercise-Nutrient Interactions In Human Skeletal Muscle, William J. Smiles
Skeletal muscle is a dynamic tissue comprising the largest protein reservoir of the human body with a rate of turnover of ~1-2% per day. Protein turnover is regulated by the coordination of intracellular systems regulating protein synthesis and breakdown that converge in a spatiotemporal manner on lysosomal organelles responsible for integrating a variety of contractile and nutritional stimuli. One such system, autophagy, which literally means to ‘self-eat,’ involves capturing of cellular material for deliver to, and disintegration by, the lysosome. The autophagic ‘cargo’ is subsequently recycled for use in synthetic reactions and thus maintenance of protein balance. As a dynamic ...