Open Access. Powered by Scholars. Published by Universities.®

Digital Commons Network™

Open Access. Powered by Scholars. Published by Universities.®

Medical Sciences

Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 10711 - 10740 of 13145

Full-Text Articles in Entire DC Network

Proteolysis Of Virulence Regulator Toxr Is Associated With Entry Of Vibrio Cholerae Into A Dormant State, Salvador Almagro-Moreno, Tae K. Kim, Karen Skorupski, Ronald K. Taylor Apr 2015

Proteolysis Of Virulence Regulator Toxr Is Associated With Entry Of Vibrio Cholerae Into A Dormant State, Salvador Almagro-Moreno, Tae K. Kim, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio Pathogenicity Island (VPI), a horizontally acquired mobile genetic element, and functions primarily in virulence gene regulation. TcpP has been shown to undergo regulated intramembrane proteolysis (RIP) in response to environmental conditions that are unfavorable for virulence gene expression. ToxR is encoded in the ancestral genome and is present in non-pathogenic strains of V. cholerae, indicating it has roles outside of the human …


Research And Design Of Supportive Exoskeletal Aides For The Physically Challengedan Initial Investigation Into The Fundamentals And Rudiments Of Building A Full Body Exoskeletonmark, Mark Jacobs Apr 2015

Research And Design Of Supportive Exoskeletal Aides For The Physically Challengedan Initial Investigation Into The Fundamentals And Rudiments Of Building A Full Body Exoskeletonmark, Mark Jacobs

Thinking Matters Symposium Archive

The purpose of this study is to provide methodology for designing exoskeletal prostheses targeted to specific pathologies associated with: Cerebral Palsy; Limb Deficiency; Spinal Pathologies; and Functional Limb Pathologies This study will extend to whole body exoskeletal structures. The project will be performed in conjunction with Shriner’s Hospital for Children in Springfield, Massachusetts; M.I.T. Bio-prosthetic Group; and finally, Massachusetts General Hospital Orthopedics Group. Further work will be done designing the necessary components for the project in Solidworks utilizing a 3D mannequin. The parts will then be fabricated using a CNC machine, first making them from foam insulation, then from wood …


The Therapeutic Role Of Turmeric In Treatment And Prevention Of Alzheimer’S Disease, Rylan M. Mcquade Apr 2015

The Therapeutic Role Of Turmeric In Treatment And Prevention Of Alzheimer’S Disease, Rylan M. Mcquade

Selected Honors Theses

As a devastating neurological condition that expends millions of lives each year, Alzheimer’s disease (AD) is a subject of intense investigation.1 Although AD has been known for over a century, the precise mechanisms that underlie AD pathogenesis and development are still poorly understood. The Alzheimer phenotype is typified by extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs), causing researchers to notice several key enzymes implicated in this process.1 Most notable are β and γ secretases (which drive Aβ plaque production) and phospholipase

A2 (which stimulates major cascade activation through the specific cleavage of fatty acyl esters). …


Different Neural Mechanisms For Causal Processing In Language And Perception: An Fmri Study, Brett B. Bankson, Dirk B. Den Ouden Apr 2015

Different Neural Mechanisms For Causal Processing In Language And Perception: An Fmri Study, Brett B. Bankson, Dirk B. Den Ouden

Communication Sciences and Disorders Faculty Articles and Research

Information that is used to establish and evaluate causal relationships between objects and events can be gleaned from many sources, especially those that rely on language and perception. For example, sentences with a verb structure using change of state verbs such as “to break” or “to freeze” imply sequential events that express understood causal relationships. At this time, little research has examined the neural correlates of causal verb processing or has compared them to the more well researched brain activity involved in perceptual causal processing. This study investigated the extent to which the evaluation of causal verbs and causal image …


The Preparatory Set: A Novel Approach To Understanding Stress, Trauma, And The Bodymind Therapies, Peter Payne, Mardi A. Crane-Godreau Apr 2015

The Preparatory Set: A Novel Approach To Understanding Stress, Trauma, And The Bodymind Therapies, Peter Payne, Mardi A. Crane-Godreau

Dartmouth Scholarship

Basic to all motile life is a differential approach/avoid response to perceived features of environment. The stages of response are initial reflexive noticing and orienting to the stimulus, preparation, and execution of response. Preparation involves a coordination of many aspects of the organism: muscle tone, posture, breathing, autonomic functions, motivational/emotional state, attentional orientation, and expectations. The organism organizes itself in relation to the challenge. We propose to call this the "preparatory set" (PS). We suggest that the concept of the PS can offer a more nuanced and flexible perspective on the stress response than do current theories. We also hypothesize …


The Cognitive Effects Of Chronic Malnutrition And Environment On Working Memory And Executive Function In Children, Kristiana E. Morgan Apr 2015

The Cognitive Effects Of Chronic Malnutrition And Environment On Working Memory And Executive Function In Children, Kristiana E. Morgan

Independent Study Project (ISP) Collection

Chronic malnutrition, or stunting, occurs frequently in many developing countries such as Uganda. Stunting hinders physical growth and has been associated with delayed cognitive development, especially in young children. This study examined the effect of stunted growth on the function of cognitive processes involving the working memory and executive functions using neuropsychological assessments. Additionally, this study compared cognitive performances among rural and urban populations to analyze the environmental background differences which may affect cognition.

Population samples of fifteen five year old children classified as rural adequately nourished, rural stunted and urban adequately nourished were examined. Tests for working memory and …


A Cost-Reducing Extracorporeal Membrane Oxygenation (Ecmo) Program Model: A Single Institution Experience., Nicholas C. Cavarocchi, S Wallace, E Y. Hong, A Tropea, J Byrne, Harrsion Pitcher, Hitoshi Hirose Mar 2015

A Cost-Reducing Extracorporeal Membrane Oxygenation (Ecmo) Program Model: A Single Institution Experience., Nicholas C. Cavarocchi, S Wallace, E Y. Hong, A Tropea, J Byrne, Harrsion Pitcher, Hitoshi Hirose

Department of Surgery Faculty Papers

BACKGROUND: The worldwide demand for ECMO support has grown. Its provision remains limited due to several factors (high cost, complicated technology, lack of expertise) that increase healthcare cost. Our goal was to assess if an intensive care unit (ICU)-run ECMO model without continuous bedside perfusionists would decrease costs while maintaining patient safety and outcomes.

METHOD: A new ECMO program was implemented in 2010, consisting of dedicated ICU multidisciplinary providers (ICU-registered nurses, mid-level providers and intensivists). In year one, we introduced an education platform, new technology and dedicated space. In year two, continuous bedside monitoring by perfusionists was removed and new …


G Protein Βγ Subunits Regulate Cardiomyocyte Hypertrophy Through A Perinuclear Golgi Phosphatidylinositol 4-Phosphate Hydrolysis Pathway., S Malik, R G Derubio, M Trembley, R Irannejad, Philip B Wedegaertner, A V Smrcka Mar 2015

G Protein Βγ Subunits Regulate Cardiomyocyte Hypertrophy Through A Perinuclear Golgi Phosphatidylinositol 4-Phosphate Hydrolysis Pathway., S Malik, R G Derubio, M Trembley, R Irannejad, Philip B Wedegaertner, A V Smrcka

Department of Biochemistry and Molecular Biology Faculty Papers

We recently identified a novel GPCR-dependent pathway for regulation of cardiac hypertrophy that depends on Golgi phosphatidylinositol 4-phosphate (PI4P) hydrolysis by a specific isoform of phospholipase C (PLC), PLCε, at the nuclear envelope. How stimuli are transmitted from cell surface GPCRs to activation of perinuclear PLCε is not clear. Here we tested the role of G protein βγ subunits. Gβγ inhibition blocked ET-1-stimulated Golgi PI4P depletion in neonatal and adult ventricular myocytes. Blocking Gβγ at the Golgi inhibited ET-1-dependent PI4P depletion and nuclear PKD activation. Translocation of Gβγ to the Golgi stimulated perinuclear Golgi PI4P depletion and nuclear PKD activation. …


Prolonged-Acting, Multi-Targeting Gallium Nanoparticles Potently Inhibit Growth Of Both Hiv And Mycobacteria In Co-Infected Human Macrophages., Prabagaran Narayanasamy, Barbara L. Switzer, Bradley E. Britigan Mar 2015

Prolonged-Acting, Multi-Targeting Gallium Nanoparticles Potently Inhibit Growth Of Both Hiv And Mycobacteria In Co-Infected Human Macrophages., Prabagaran Narayanasamy, Barbara L. Switzer, Bradley E. Britigan

Journal Articles: Pathology and Microbiology

Human immunodeficiency virus (HIV) infection and Mycobacterium tuberculosis (TB) are responsible for two of the major global human infectious diseases that result in significant morbidity, mortality and socioeconomic impact. Furthermore, severity and disease prevention of both infections is enhanced by co-infection. Parallel limitations also exist in access to effective drug therapy and the emergence of resistance. Furthermore, drug-drug interactions have proven problematic during treatment of co-incident HIV and TB infections. Thus, improvements in drug access and simplified treatment regimens are needed immediately. One of the key host cells infected by both HIV and TB is the mononuclear phagocyte (MP; monocyte, …


Deletion Of Shank1 Has Minimal Effects On The Molecular Composition And Function Of Glutamatergic Afferent Postsynapses In The Mouse Inner Ear, Jeremy P. Braude, Sarath Vijayakumar, Katherine Baumgarner, Rebecca Laurine, Timothy A. Jones, Sherri M. Jones, Sonya J. Pyott Mar 2015

Deletion Of Shank1 Has Minimal Effects On The Molecular Composition And Function Of Glutamatergic Afferent Postsynapses In The Mouse Inner Ear, Jeremy P. Braude, Sarath Vijayakumar, Katherine Baumgarner, Rebecca Laurine, Timothy A. Jones, Sherri M. Jones, Sonya J. Pyott

Department of Special Education and Communication Disorders: Faculty Publications

Abstract

Shank proteins (1-3) are considered the master organizers of glutamatergic postsynaptic densities in the central nervous system, and the genetic deletion of either Shank1, 2, or 3 results in altered composition, form, and strength of glutamatergic postsynapses. To investigate the contribution of Shank proteins to glutamatergic afferent synapses of the inner ear and especially cochlea, we used immunofluorescence and quantitative real time PCR to determine the expression of Shank1, 2, and 3 in the cochlea. Because we found evidence for expression of Shank1 but not 2 and 3, we investigated the morphology, composition, and function of afferent postsynaptic densities …


Lymph Node But Not Intradermal Injection Site Macrophages Are Critical For Germinal Center Formation And Antibody Responses To Rabies Vaccination., Andrew G Lytle, Shixue Shen, James Mcgettigan Mar 2015

Lymph Node But Not Intradermal Injection Site Macrophages Are Critical For Germinal Center Formation And Antibody Responses To Rabies Vaccination., Andrew G Lytle, Shixue Shen, James Mcgettigan

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: Replication-deficient rabies virus (RABV)-based vaccines induce rapid and potent antibody responses via T cell-independent and T cell-dependent mechanisms. To further investigate early events in vaccine-induced antibody responses against RABV infections, we studied the role of macrophages as mediators of RABV-based vaccine immunogenicity. In this report, we show that a recombinant matrix gene-deleted RABV-based vaccine (rRABV-ΔM) infects and activates primary murine macrophages in vitro. Immunization of mice with live RABV-based vaccines results in accumulation of macrophages at the site of immunization, which suggests that macrophages in tissues support the development of effective anti-RABV B cell responses. However, we show that …


Regulation Of Mammalian Nucleotide Metabolism And Biosynthesis, Andrew N. Lane, Teresa W-M Fan Feb 2015

Regulation Of Mammalian Nucleotide Metabolism And Biosynthesis, Andrew N. Lane, Teresa W-M Fan

Toxicology and Cancer Biology Faculty Publications

Nucleotides are required for a wide variety of biological processes and are constantly synthesized de novo in all cells. When cells proliferate, increased nucleotide synthesis is necessary for DNA replication and for RNA production to support protein synthesis at different stages of the cell cycle, during which these events are regulated at multiple levels. Therefore the synthesis of the precursor nucleotides is also strongly regulated at multiple levels. Nucleotide synthesis is an energy intensive process that uses multiple metabolic pathways across different cell compartments and several sources of carbon and nitrogen. The processes are regulated at the transcription level by …


Tumor Cell Targeting By Iron Oxide Nanoparticles Is Dominated By Different Factors In Vitro Versus In Vivo, Christian Ndong, Jennifer A. Tate, Warren C. Kett, Jaya Batra, Eugene Demidenko, Lionel D. Lewis, P. Jack Hoopes, Tillmann U. Gerngross, Karl E. Griswold Feb 2015

Tumor Cell Targeting By Iron Oxide Nanoparticles Is Dominated By Different Factors In Vitro Versus In Vivo, Christian Ndong, Jennifer A. Tate, Warren C. Kett, Jaya Batra, Eugene Demidenko, Lionel D. Lewis, P. Jack Hoopes, Tillmann U. Gerngross, Karl E. Griswold

Dartmouth Scholarship

Realizing the full potential of iron oxide nanoparticles (IONP) for cancer diagnosis and therapy requires selective tumor cell accumulation. Here, we report a systematic analysis of two key determinants for IONP homing to human breast cancers: (i) particle size and (ii) active vs passive targeting. In vitro, molecular targeting to the HER2 receptor was the dominant factor driving cancer cell association. In contrast, size was found to be the key determinant of tumor accumulation in vivo, where molecular targeting increased tumor tissue concentrations for 30 nm but not 100 nm IONP. Similar to the in vitro results, PEGylation …


Overexpression Of Sox11 Promotes Corticospinal Tract Regeneration After Spinal Injury While Interfering With Functional Recovery, Zimei Wang, Ashley Reynolds, Adam Kirry, Christopher Nienhaus, Murray G. Blackmore Feb 2015

Overexpression Of Sox11 Promotes Corticospinal Tract Regeneration After Spinal Injury While Interfering With Functional Recovery, Zimei Wang, Ashley Reynolds, Adam Kirry, Christopher Nienhaus, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Embryonic neurons, peripheral neurons, and CNS neurons in zebrafish respond to axon injury by initiating pro-regenerative transcriptional programs that enable axons to extend, locate appropriate targets, and ultimately contribute to behavioral recovery. In contrast, many long-distance projection neurons in the adult mammalian CNS, notably corticospinal tract (CST) neurons, display a much lower regenerative capacity. To promote CNS repair, a long-standing goal has been to activate pro-regenerative mechanisms that are normally missing from injured CNS neurons. Sox11 is a transcription factor whose expression is common to a many types of regenerating neurons, but it is unknown whether suboptimal Sox11 expression contributes …


Shbg Gene Polymorphism (Rs1799941) Associates With Metabolic Syndrome In Children And Adolescents, Marquitta J. White, Fatih Eren, Deniz Agirbasli, Scott M. Williams, Mehmet Agirbasli Feb 2015

Shbg Gene Polymorphism (Rs1799941) Associates With Metabolic Syndrome In Children And Adolescents, Marquitta J. White, Fatih Eren, Deniz Agirbasli, Scott M. Williams, Mehmet Agirbasli

Dartmouth Scholarship

Background: Metabolic syndrome (MetS) is a complex disorder characterized by coexistence of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD). The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents.

Methods: Genetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs), previously shown to modulate lipid or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish …


Disrupting Sumoylation Enhances Transcriptional Function And Ameliorates Polyglutamine Androgen Receptor-Mediated Disease., Jason P Chua, Satya L Reddy, Zhigang Yu, Elisa Giorgetti, Heather L Montie, Sarmistha Mukherjee, Jake Higgins, Richard C Mceachin, Diane M Robins, Diane E Merry, Jorge A Iñiguez-Lluhí, Andrew P Lieberman Feb 2015

Disrupting Sumoylation Enhances Transcriptional Function And Ameliorates Polyglutamine Androgen Receptor-Mediated Disease., Jason P Chua, Satya L Reddy, Zhigang Yu, Elisa Giorgetti, Heather L Montie, Sarmistha Mukherjee, Jake Higgins, Richard C Mceachin, Diane M Robins, Diane E Merry, Jorge A Iñiguez-Lluhí, Andrew P Lieberman

Department of Biochemistry and Molecular Biology Faculty Papers

Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR) causes neuromuscular degeneration in individuals with spinobulbar muscular atrophy (SBMA). PolyQ AR has diminished transcriptional function and exhibits ligand-dependent proteotoxicity, features that have both been implicated in SBMA; however, the extent to which altered AR transcriptional function contributes to pathogenesis remains controversial. Here, we sought to dissociate effects of diminished AR function from polyQ-mediated proteotoxicity by enhancing the transcriptional activity of polyQ AR. To accomplish this, we bypassed the inhibitory effect of AR SUMOylation (where SUMO indicates small ubiquitin-like modifier) by mutating conserved lysines in the polyQ AR that …


Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains, Zhongle Liu, Lawrence C. Myers Feb 2015

Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains, Zhongle Liu, Lawrence C. Myers

Dartmouth Scholarship

Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their …


Elucidation Of The Cellular And Molecular Mechanisms Of Missense Mutations Associated With Familial Exudative Vitreoretinopathy And Congenital Myasthenic Syndrome, Reham Mahmoud Mohammed Milhem Feb 2015

Elucidation Of The Cellular And Molecular Mechanisms Of Missense Mutations Associated With Familial Exudative Vitreoretinopathy And Congenital Myasthenic Syndrome, Reham Mahmoud Mohammed Milhem

Dissertations

The endoplasmic reticulum (ER), within eukaryotic cells, is a hub for protein folding and assembly. Misfolded proteins and unassembled subunits of protein complexes are retained in the ER and degraded by a process termed endoplasmic reticulum associated degradation (ERAD). Frizzled class receptor 4 (FZD4) and muscle, skeletal, receptor tyrosine kinase (MuSK) are Wnt receptors. These proteins contain the frizzled cysteine-rich domain (Fz-CRD) required for dimerization in the ER. Mutations in FZD4 and MuSK genes are known to cause familial exudative vitreoretinopathy (FEVR, an autosomal dominant disease) and congenital myasthenic syndrome (CMS, an autosomal recessive disease), respectively. It was hypothesized that …


Tcr Alpha Lcr And Non-Lcr Cis-Elements Contributing To Tissue Specific Expression Of The Tcr Alpha Gene In Thymic And Peripheral T Cells, Martina Kucerova-Levisohn Feb 2015

Tcr Alpha Lcr And Non-Lcr Cis-Elements Contributing To Tissue Specific Expression Of The Tcr Alpha Gene In Thymic And Peripheral T Cells, Martina Kucerova-Levisohn

Dissertations, Theses, and Capstone Projects

Orchestrated expression of multiple genes residing in the complex TCRα/δ/Dad1 locus requires tight control from multiple cis-acting elements. The TCRα locus control region (LCR), is positioned between TCRα and Dad1 gene, and has been implicated in the differential expression of both genes. In this study, we focus our work on the hypersensitive site (HS)1 prime (HS1'), located 3' of the classical Eα enhancer, within the TCRα LCR. We investigated its non- redundant role in TCRα expression in thymic and peripheral T cells as assayed by in vivo and in vitro studies. Furthermore, formation of HS1' in both lymphoid and …


Validation Of In Vivo 2d Displacements From Spiral Cine Dense At 3t, Gregory J. Wehner, Jonathan D. Suever, Christopher M. Haggerty, Linyuan Jing, David K. Powell, Sean M. Hamlet, Jonathan D. Grabau, Walter Dimitri Mojsejenko, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt Jan 2015

Validation Of In Vivo 2d Displacements From Spiral Cine Dense At 3t, Gregory J. Wehner, Jonathan D. Suever, Christopher M. Haggerty, Linyuan Jing, David K. Powell, Sean M. Hamlet, Jonathan D. Grabau, Walter Dimitri Mojsejenko, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. Due to the stimulated echo, the signal is inherently low and fades through the cardiac cycle. To compensate, a spiral acquisition has been used at 1.5T. This spiral sequence has not been validated at 3T, where the increased signal would be valuable, but field inhomogeneities may result in measurement errors. We hypothesized that spiral cine DENSE is valid at 3T and tested this hypothesis by measuring displacement errors at both 1.5T and 3T in vivo.

METHODS: Two-dimensional spiral cine DENSE and tagged …


Il-1Α Signaling Is Critical For Leukocyte Recruitment After Pulmonary Aspergillus Fumigatus Challenge, Alayna K. Caffrey, Margaret M. Lehmann, Julianne M. Zickovich, Vanessa Espinosa, Kelly M. Shepardson, Christopher P. Watschke, Kimberly M. Hilmer, Arsa Thammahong, Bridget M. Barker, Amariliz Rivera, Robert A. Cramer, Joshua J. Obar Jan 2015

Il-1Α Signaling Is Critical For Leukocyte Recruitment After Pulmonary Aspergillus Fumigatus Challenge, Alayna K. Caffrey, Margaret M. Lehmann, Julianne M. Zickovich, Vanessa Espinosa, Kelly M. Shepardson, Christopher P. Watschke, Kimberly M. Hilmer, Arsa Thammahong, Bridget M. Barker, Amariliz Rivera, Robert A. Cramer, Joshua J. Obar

Dartmouth Scholarship

Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how A. fumigatus growth is controlled in the respiratory tract is developing, but still limited. Alveolar macrophages, lung resident macrophages, and airway epithelial cells constitute the first lines of defense against inhaled A. fumigatus conidia. Subsequently, neutrophils and inflammatory CCR2+ monocytes are recruited to the respiratory tract to prevent fungal growth. However, the mechanism of neutrophil and macrophage recruitment to the respiratory tract after A. fumigatus exposure remains an area of ongoing investigation. Here we show that A. fumigatus pulmonary challenge induces expression of the inflammasome-dependent cytokines …


Hidden Formaldehyde In E-Cigarette Aerosols, R. Paul Jensen, Wentai Luo, James F. Pankow, Robert M. Strongin, David H. Peyton Jan 2015

Hidden Formaldehyde In E-Cigarette Aerosols, R. Paul Jensen, Wentai Luo, James F. Pankow, Robert M. Strongin, David H. Peyton

Chemistry Faculty Publications and Presentations

This letter reports a chemical analysis of vapor from electronic cigarettes that shows high levels of formaldehyde, a known carcinogen. The authors project that the associated incremental lifetime risk of cancer could be higher than that from long-term smoking.


The Tmao-Generating Enzyme Flavin Monooxygenase 3 Is A Central Regulator Of Cholesterol Balance, Manya Warrier, Diana M. Shih, Amy C. Burrows, Daniel Ferguson, Anthony D. Gromovsky, Amanda L. Brown, Stephanie Marshall, Allison Mcdaniel, Rebecca C. Schugar, Zeneng Wang, Jessica Sacks, Xin Rong, Thomas De Aguiar Vallim, Jeff Chou, Pavlina T. Ivanova, David S. Myers, H. Alex Brown, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Xiuli Liu, Paolo Parini, Peter Tontonoz, Aldon J. Lusis, Stanley L. Hazen, Ryan E. Temel, J. Mark Brown Jan 2015

The Tmao-Generating Enzyme Flavin Monooxygenase 3 Is A Central Regulator Of Cholesterol Balance, Manya Warrier, Diana M. Shih, Amy C. Burrows, Daniel Ferguson, Anthony D. Gromovsky, Amanda L. Brown, Stephanie Marshall, Allison Mcdaniel, Rebecca C. Schugar, Zeneng Wang, Jessica Sacks, Xin Rong, Thomas De Aguiar Vallim, Jeff Chou, Pavlina T. Ivanova, David S. Myers, H. Alex Brown, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Xiuli Liu, Paolo Parini, Peter Tontonoz, Aldon J. Lusis, Stanley L. Hazen, Ryan E. Temel, J. Mark Brown

Saha Cardiovascular Research Center Faculty Publications

Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here, we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT) and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER) stress …


Mitochondrial Ca(2+) Uptake By The Voltage-Dependent Anion Channel 2 Regulates Cardiac Rhythmicity., Hirohito Shimizu, Johann Schredelseker, Jie Huang, Kui Lu, Shamim Naghdi, Fei Lu, Sarah Franklin, Hannah Dg Fiji, Kevin Wang, Huanqi Zhu, Cheng Tian, Billy Lin, Haruko Nakano, Amy Ehrlich, Junichi Nakai, Adam Z Stieg, James K Gimzewski, Atsushi Nakano, Joshua I. Goldhaber, Thomas M. Vondriska, György Hajnóczky, Ohyun Kwon, Jau-Nian Chen Jan 2015

Mitochondrial Ca(2+) Uptake By The Voltage-Dependent Anion Channel 2 Regulates Cardiac Rhythmicity., Hirohito Shimizu, Johann Schredelseker, Jie Huang, Kui Lu, Shamim Naghdi, Fei Lu, Sarah Franklin, Hannah Dg Fiji, Kevin Wang, Huanqi Zhu, Cheng Tian, Billy Lin, Haruko Nakano, Amy Ehrlich, Junichi Nakai, Adam Z Stieg, James K Gimzewski, Atsushi Nakano, Joshua I. Goldhaber, Thomas M. Vondriska, György Hajnóczky, Ohyun Kwon, Jau-Nian Chen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac function. To dissect the regulatory network of cardiac Ca(2+) handling, we performed a chemical suppressor screen on zebrafish tremblor embryos, which suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent activity to restore coordinated contractions in tremblor. We show that efsevin binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the transfer of Ca(2+) from intracellular stores into mitochondria. In cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+) sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and irregular contractions. We further show that overexpression …


In Vivo Cigarette Smoke Exposure Decreases Ccl20, Slpi, And Bd-1 Secretion By Human Primary Nasal Epithelial Cells, James Jukosky, Benoit J. Gosselin, Leah Foley, Tenzin Dechen, Steven Fiering, Mardi A. Crane-Godreau Jan 2015

In Vivo Cigarette Smoke Exposure Decreases Ccl20, Slpi, And Bd-1 Secretion By Human Primary Nasal Epithelial Cells, James Jukosky, Benoit J. Gosselin, Leah Foley, Tenzin Dechen, Steven Fiering, Mardi A. Crane-Godreau

Dartmouth Scholarship

Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of …


The Cell's Antenna And Bending With The Flow, Surya M. Nauli, Kimberly F. Atkinson, Sarmed H. Kathem Jan 2015

The Cell's Antenna And Bending With The Flow, Surya M. Nauli, Kimberly F. Atkinson, Sarmed H. Kathem

Pharmacy Faculty Articles and Research

Polycystic kidney disease (PKD) is the most common life-threatening genetic disease worldwide – affecting about 12.5 million people. Patients with the condition have multiple fluid-filled cysts in their kidneys that lead to a massive enlargement of the organ and gradual worsening of its function, as well as complete failure in many cases. The lack of available treatment means patients may eventually require regular dialysis or a kidney transplant.


Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield Jan 2015

Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield

Dartmouth Scholarship

Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes …


Human Stem Cells: Is It Possible To Limit Pluripotent Human Stem Cells To Differentiate Into Specific Tissue Or Organ?, Chaya Korf Jan 2015

Human Stem Cells: Is It Possible To Limit Pluripotent Human Stem Cells To Differentiate Into Specific Tissue Or Organ?, Chaya Korf

The Science Journal of the Lander College of Arts and Sciences

It would seem that differentiation of stem cells is the remedy of modern times. Yet stem cell research is more complex that the public may recognize and is still in the developmental stage. Recent breakthroughs show promise; various guidelines provide structure to this growing field but it is not ready for gross public application. The objective of this paper is to research various different methods of stem cell production and application. Methods included reviewing articles and studies to evaluate the process in production of affective stem cells. There are many therapies that illustrate this research. Upon completing and explaining this …


Feasibility Of Simultaneous Whole-Brain Imaging On An Integrated Pet-Mri System Using An Enhanced 2-Point Dixon Attenuation Correction Method., Udunna C Anazodo, Jonathan D Thiessen, Tracy Ssali, Jonathan Mandel, Matthias Günther, John Butler, William Pavlosky, Frank S Prato, R Terry Thompson, Keith S St Lawrence Jan 2015

Feasibility Of Simultaneous Whole-Brain Imaging On An Integrated Pet-Mri System Using An Enhanced 2-Point Dixon Attenuation Correction Method., Udunna C Anazodo, Jonathan D Thiessen, Tracy Ssali, Jonathan Mandel, Matthias Günther, John Butler, William Pavlosky, Frank S Prato, R Terry Thompson, Keith S St Lawrence

Medical Biophysics Publications

PURPOSE: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored.

METHODS: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose …


To Pair Or Not To Pair: Sources Of Social Variability With White-Faced Saki Monkeys (Pithecia Pithecia) As A Case Study, Cynthia Thompson Jan 2015

To Pair Or Not To Pair: Sources Of Social Variability With White-Faced Saki Monkeys (Pithecia Pithecia) As A Case Study, Cynthia Thompson

Open Access Publishing Support Funded Articles

Intraspecific variability in social systems is gaining increased recognition in primatology. Many primate species display variability in pair-living social organizations through incorporating extra adults into the group. While numerous models exist to explain primate pair-living, our tools to assess how and why variation in this trait occurs are currently limited. Here I outline an approach which: (i) utilizes conceptual models to identify the selective forces driving pair-living; (ii) outlines novel possible causes for variability in social organization; and (iii) conducts a holistic species-level analysis of social behavior to determine the factors contributing to variation in pair-living. A case study on …