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Articles 41071 - 41100 of 45191
Full-Text Articles in Medicine and Health Sciences
Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry
Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry
Nebraska Center for Virology: Faculty Publications
Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5- immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in …
Intracranial Eeg Reveals A Time- And Frequency-Specific Role For The Right Inferior Frontal Gyrus And Primary Motor Cortex In Stopping Initiated Responses, Nicole Swann, Nitin Tandon, Ryan Canolty, Timothy M Ellmore, Linda K Mcevoy, Stephen Dreyer, Michael Disano, Adam R Aron
Intracranial Eeg Reveals A Time- And Frequency-Specific Role For The Right Inferior Frontal Gyrus And Primary Motor Cortex In Stopping Initiated Responses, Nicole Swann, Nitin Tandon, Ryan Canolty, Timothy M Ellmore, Linda K Mcevoy, Stephen Dreyer, Michael Disano, Adam R Aron
Faculty, Staff and Student Publications
Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band ( approximately 16 Hz) …
Pancreatic Cancer Cells Resistance To Gemcitabine: The Role Of Muc4 Mucin., S. Bafna, Sukhwinder Kaur, N. Momi, Surinder K. Batra
Pancreatic Cancer Cells Resistance To Gemcitabine: The Role Of Muc4 Mucin., S. Bafna, Sukhwinder Kaur, N. Momi, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
BACKGROUND: A major obstacle to the successful management of pancreatic cancer is to acquire resistance to the existing chemotherapeutic agents. Resistance to gemcitabine, the standard first-line chemotherapeutic agent for advanced and metastatic pancreatic cancer, is mainly attributed to an altered apoptotic threshold in the pancreatic cancer. The MUC4 transmembrane glycoprotein is aberrantly overexpressed in the pancreatic cancer and recently, has been shown to increase pancreatic tumour cell growth by the inhibition of apoptosis.
METHODS: Effect of MUC4 on pancreatic cancer cells resistance to gemcitabine was studied in MUC4-expressing and MUC4-knocked down pancreatic cancer cell lines after treatment with gemcitabine by …
Mast Cell–Derived Particles Deliver Peripheral Signals To Remote Lymph Nodes, Christian A. Kunder, Ashley L. St. John, Guojie Li, Kam W. Leong, Brent Berwin, Herman F. Staats, Soman N. Abraham
Mast Cell–Derived Particles Deliver Peripheral Signals To Remote Lymph Nodes, Christian A. Kunder, Ashley L. St. John, Guojie Li, Kam W. Leong, Brent Berwin, Herman F. Staats, Soman N. Abraham
Dartmouth Scholarship
During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues.
Acetaminophen Combinations Protect Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Ryan G. Morrison, Lucy Dornon, Joseph P. Laurino, Sandra M. Walker, Mark Studeny, Paulette S. Wehner, Kevin M. Rice, Miaozong Wu, Eric R. Blough
Acetaminophen Combinations Protect Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Ryan G. Morrison, Lucy Dornon, Joseph P. Laurino, Sandra M. Walker, Mark Studeny, Paulette S. Wehner, Kevin M. Rice, Miaozong Wu, Eric R. Blough
MIIR Faculty Research
This study tested if acetaminophen, N-methyl-D-glucamine dithiocarbamate (NMGDTC), deferoxamine, and combinations of these agents reduce excess iron content, prevent iron-induced pathology, reduce cardiac arrhythmias, and reduce mortality in iron-overloaded gerbils. Eight groups of 16 gerbils received iron dextran injections (ferric hydroxide dextran complex, 120 mg/kg, ip) or saline solution (controls) twice/wk for 8 wk. The 8 groups were treated every Monday, Wednesday, and Friday with one of the following: saline control, acetaminophen, 150 mg/kg, ip), acetaminophen (150 mg/kg, po), deferoxamine, 83 mg/kg, ip), NMGDTC (200 mg/kg, ip), or combinations of acetaminophen (75 mg/kg) with deferoxamine (42 mg/kg, each ip, separately) …
Assembly Of Arenavirus Envelope Glycoprotein Gpc In Detergent-Soluble Membrane Microdomains, Sudhakar S. Agnihothram, Brooke Dancho, Kenneth W. Grant, Mark L. Grimes, Douglas S. Lyles, Jack H. Nunberg
Assembly Of Arenavirus Envelope Glycoprotein Gpc In Detergent-Soluble Membrane Microdomains, Sudhakar S. Agnihothram, Brooke Dancho, Kenneth W. Grant, Mark L. Grimes, Douglas S. Lyles, Jack H. Nunberg
Biomedical and Pharmaceutical Sciences Faculty Publications
The family Arenaviridae includes a number of highly pathogenic viruses that are responsible for acute hemorrhagic fevers in humans. Genetic diversity among arenavirus species in their respective rodent hosts supports the continued emergence of new pathogens. In the absence of available vaccines or therapeutic agents, the hemorrhagic fever arenaviruses remain a serious public health and biodefense concern. Arenaviruses are enveloped virions that assemble and bud from the plasma membrane. In this study, we have characterized the microdomain organization of the virus envelope glycoprotein (GPC) on the cell surface by using immunogold electron microscopy. We find that Junin virus (JUNV) GPC …
The Production Of Antibody By Invading B Cells Is Required For The Clearance Of Rabies Virus From The Central Nervous System., D Craig Hooper, Timothy W Phares, Marzena J Fabis, Anirban Roy
The Production Of Antibody By Invading B Cells Is Required For The Clearance Of Rabies Virus From The Central Nervous System., D Craig Hooper, Timothy W Phares, Marzena J Fabis, Anirban Roy
Department of Cancer Biology Faculty Papers
BACKGROUND: The pathogenesis of rabies is associated with the inability to deliver immune effectors across the blood-brain barrier and to clear virulent rabies virus from CNS tissues. However, the mechanisms that facilitate immune effector entry into CNS tissues are induced by infection with attenuated rabies virus.
METHODOLOGY/PRINCIPAL FINDINGS: Infection of normal mice with attenuated rabies virus but not immunization with killed virus can promote the clearance of pathogenic rabies virus from the CNS. T cell activity in B cell-deficient mice can control the replication of attenuated virus in the CNS, but viral mRNA persists. Low levels of passively administered rabies …
Intracellular Bacteria Encode Inhibitory Snare-Like Proteins., Fabienne Paumet, Jordan Wesolowski, Alejandro Garcia-Diaz, Cedric Delevoye, Nathalie Aulner, Howard A Shuman, Agathe Subtil, James E Rothman
Intracellular Bacteria Encode Inhibitory Snare-Like Proteins., Fabienne Paumet, Jordan Wesolowski, Alejandro Garcia-Diaz, Cedric Delevoye, Nathalie Aulner, Howard A Shuman, Agathe Subtil, James E Rothman
Department of Microbiology and Immunology Faculty Papers
Pathogens use diverse molecular machines to penetrate host cells and manipulate intracellular vesicular trafficking. Viruses employ glycoproteins, functionally and structurally similar to the SNARE proteins, to induce eukaryotic membrane fusion. Intracellular pathogens, on the other hand, need to block fusion of their infectious phagosomes with various endocytic compartments to escape from the degradative pathway. The molecular details concerning the mechanisms underlying this process are lacking. Using both an in vitro liposome fusion assay and a cellular assay, we showed that SNARE-like bacterial proteins block membrane fusion in eukaryotic cells by directly inhibiting SNARE-mediated membrane fusion. More specifically, we showed that …
Airway Smooth Muscle As An Immunomodulatory Cell., Gautam Damera, Omar Tliba, Reynold A. Panettieri, Jr.
Airway Smooth Muscle As An Immunomodulatory Cell., Gautam Damera, Omar Tliba, Reynold A. Panettieri, Jr.
College of Pharmacy Faculty Papers
Although pivotal in regulating bronchomotor tone in asthma, airway smooth muscle (ASM) also modulates airway inflammation in asthma. ASM myocytes secrete or express a wide array of immunomodulatory mediators in response to extracellular stimuli, and in chronic severe asthma, increases in ASM mass may also render the airway irreversibly obstructed. Although the mechanisms by which ASM secretes cytokines and chemokines are shared with those regulating immune cells, there exist unique ASM signaling pathways that may provide novel therapeutic targets. This review provides an overview of our current understanding of the proliferative as well as synthetic properties of ASM.
Transcriptional Regulation Of Cytokine Function In Airway Smooth Muscle Cells., Deborah Clarke, Gautam Damera, Maria B. Sukkar, Omar Tliba
Transcriptional Regulation Of Cytokine Function In Airway Smooth Muscle Cells., Deborah Clarke, Gautam Damera, Maria B. Sukkar, Omar Tliba
College of Pharmacy Faculty Papers
The immuno-modulatory properties of airway smooth muscle have become of increasing importance in our understanding of the mechanisms underlying chronic inflammation and structural remodeling of the airway wall in asthma and chronic obstructive pulmonary disease (COPD). ASM cells respond to many cytokines, growth factors and lipid mediators to produce a wide array of immuno-modulatory molecules which may in turn orchestrate and perpetuate the disease process in asthma and COPD. Despite numerous studies of the cellular effects of cytokines on cultured ASM, few have identified intracellular signaling pathways by which cytokines modulate or induce these cellular responses. In this review we …
Foxp3-Expressing T Regulatory Cells (T-Regs) Increase With The Severity Of Active Disease In Chronic Hepatitis C, Adam D. Toll, Md, John L. Farber, Md
Foxp3-Expressing T Regulatory Cells (T-Regs) Increase With The Severity Of Active Disease In Chronic Hepatitis C, Adam D. Toll, Md, John L. Farber, Md
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
The hepatitis C virus (HCV) leads to chronic disease in 80% of those infected and is associated with a chronic inflammatory response that is mediated by both cytokine producing (CD4+) and cytotoxic T cells (CD8+). FoxP3-expressing, CD4+, CD25+T cells (T-regs) are a subset of T lymphocytes that inhibit immune responsiveness and thereby control immunological reactions. Whether FoxP3+ T regulatory cell-mediated suppression is a factor in HCV persistence and/or the course of chronic liver injury has not been defined. In order to assess the association between these T regulatory cells and the severity of chronic hepatitis C, we evaluated liver biopsies …
Establishing The Purity Of Mononuclear Cell Preparations Using Morphology And Flow Cytometry, Adam Holtz, Bs, Adam D. Toll, Md, Susan W. Burkholder, Md, Alicia M. Carlin, Ba, Linda F. Blumstein, Bs, Kathleen A. Schroeder, Bs, Eric M. Behling, Md, Tina B. Edmonston, Md
Establishing The Purity Of Mononuclear Cell Preparations Using Morphology And Flow Cytometry, Adam Holtz, Bs, Adam D. Toll, Md, Susan W. Burkholder, Md, Alicia M. Carlin, Ba, Linda F. Blumstein, Bs, Kathleen A. Schroeder, Bs, Eric M. Behling, Md, Tina B. Edmonston, Md
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Context: Simple tandem repeat loci are used to track bone marrow engraftment using mononuclear buffy coat cells and T-cells. Poor isolation purity of these subpopulations can result in lower analytical sensitivity of the bone marrow engraftment assay by diluting the cell population in question with other nucleated cells. Validation of the mononuclear cell preparation can be performed by flow cytometry or by counting cell populations on the slide. Conclusions: Our results show that the purity of the Histopaque-1077 mononuclear cell preparation is excellent and that morphology may be sufficient to validate the mononuclear cell isolation method if flow cytometry is …
Inflammasome-Dependent Caspase-1 Activation In Cervical Epithelial Cells Stimulates Growth Of The Intracellular Pathogen Chlamydia Trachomatis, Ali A. Abdul-Sater, Evonne Koo, Georg Hacker, David M. Ojcius
Inflammasome-Dependent Caspase-1 Activation In Cervical Epithelial Cells Stimulates Growth Of The Intracellular Pathogen Chlamydia Trachomatis, Ali A. Abdul-Sater, Evonne Koo, Georg Hacker, David M. Ojcius
All Dugoni School of Dentistry Faculty Articles
Inflammasomes have been extensively characterized in monocytes and macrophages, but not in epithelial cells, which are the preferred host cells for many pathogens. Here we show that cervical epithelial cells express a functional inflammasome. Infection of the cells by Chlamydia trachomatis leads to activation of caspase-1, through a process requiring the NOD-like receptor family member NLRP3 and the inflammasome adaptor protein ASC. Secretion of newly synthesized virulence proteins from the chlamydial vacuole through a type III secretion apparatus results in efflux of K+ through glibenclamide-sensitive K+ channels, which in turn stimulates production of reactive oxygen species. Elevated levels of reactive …
Jnk1-Dependent Puma Expression Contributes To Hepatocyte Lipoapoptosis., Sophie C. Cazanave, Justin L. Mott, Nafisa A. Elmi, Steven F. Bronk, Nathan W. Werneburg, Yuko Akazawa, Alisan Kahraman, Sean P. Garrison, Gerard P. Zambetti, Michael R. Charlton, Gregory J. Gores
Jnk1-Dependent Puma Expression Contributes To Hepatocyte Lipoapoptosis., Sophie C. Cazanave, Justin L. Mott, Nafisa A. Elmi, Steven F. Bronk, Nathan W. Werneburg, Yuko Akazawa, Alisan Kahraman, Sean P. Garrison, Gerard P. Zambetti, Michael R. Charlton, Gregory J. Gores
Journal Articles: Biochemistry & Molecular Biology
Free fatty acids (FFA) induce hepatocyte lipoapoptosis by a c-Jun N-terminal kinase (JNK)-dependent mechanism. However, the cellular processes by which JNK engages the core apoptotic machinery during lipotoxicity, especially activation of BH3-only proteins, remain incompletely understood. Thus, our aim was to determine whether JNK mediates induction of BH3-only proteins during hepatocyte lipoapoptosis. The saturated FFA palmitate, but not the monounsaturated FFA oleate, induces an increase in PUMA mRNA and protein levels. Palmitate induction of PUMA was JNK1-dependent in primary murine hepatocytes. Palmitate-mediated PUMA expression was inhibited by a dominant negative c-Jun, and direct binding of a phosphorylated c-Jun containing the …
Role Of Mammalian Ecdysoneless In Cell Cycle Regulation., Jun Hyun Kim, Channabasavaiah B. Gurumurthy, Mayumi Naramura, Ying Zhang, Andrew T. Dudley, Lynn Doglio, Hamid Band, Vimla Band
Role Of Mammalian Ecdysoneless In Cell Cycle Regulation., Jun Hyun Kim, Channabasavaiah B. Gurumurthy, Mayumi Naramura, Ying Zhang, Andrew T. Dudley, Lynn Doglio, Hamid Band, Vimla Band
Journal Articles: Genetics, Cell Biology & Anatomy
The Ecdysoneless (Ecd) protein is required for cell-autonomous roles in development and oogenesis in Drosophila, but the function of its evolutionarily conserved mammalian orthologs is not clear. To study the cellular function of Ecd in mammalian cells, we generated Ecd(lox/lox) mouse embryonic fibroblast cells from Ecd floxed mouse embryos. Cre-mediated deletion of Ecd in Ecd(lox/lox) mouse embryonic fibroblasts led to a proliferative block due to a delay in G(1)-S cell cycle progression; this defect was reversed by the introduction of human Ecd. Loss of Ecd led to marked down-regulation of E2F target gene expression. Furthermore, Ecd directly bound to Rb …
Phosphoinositides And Snare Chaperones Synergistically Assemble And Remodel Snare Complexes For Membrane Fusion, Joji Mima, William Wickner
Phosphoinositides And Snare Chaperones Synergistically Assemble And Remodel Snare Complexes For Membrane Fusion, Joji Mima, William Wickner
Dartmouth Scholarship
Yeast vacuole fusion requires 4 SNAREs, 2 SNARE chaperone systems (Sec17p/Sec18p/ATP and the HOPS complex), and 2 phosphoinositides, phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. By reconstituting proteoliposomal fusion with purified components, we now show that phosphoinositides have 4 distinct roles: PI(3)P is recognized by the PX domain of the SNARE Vam7p; PI(3)P enhances the capacity of membrane-bound SNAREs to drive fusion in the absence of SNARE chaperones; either PI(3)P or PI(4,5)P2 can activate SNARE chaperones for the recruitment of Vam7p into fusion-competent SNARE complexes; and either PI(3)P or PI(4,5)P2 strikingly promotes synergistic SNARE complex remodeling …
The Human Rna Polymerase Ii-Associated Factor 1 (Hpaf1): A New Regulator Of Cell-Cycle Progression., Nicolas Moniaux, Christophe Nemos, Shonali Deb, Bing Zhu, Irena Dornreiter, Michael A. Hollingsworth, Surinder K. Batra
The Human Rna Polymerase Ii-Associated Factor 1 (Hpaf1): A New Regulator Of Cell-Cycle Progression., Nicolas Moniaux, Christophe Nemos, Shonali Deb, Bing Zhu, Irena Dornreiter, Michael A. Hollingsworth, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
BACKGROUND: The human PAF (hPAF) complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. Further, the yeast homolog of hPaf1 has a role in regulating the expression of a subset of genes involved in the cell-cycle. We therefore investigated the role of hPaf1 during progression of the cell-cycle.
METHODOLOGY/FINDINGS: Herein, we report that the expression of hPaf1, a subunit of the hPAF complex, increases with cell-cycle progression and is regulated in a cell-cycle dependant manner. hPaf1 specifically regulates a subclass of genes directly implicated in cell-cycle progression during G1/S, S/G2, and G2/M. …
Long-Term Immunity To Lethal Acute Or Chronic Type Ii Toxoplasma Gondii Infection Is Effectively Induced In Genetically Susceptible C57bl/6 Mice By Immunization With An Attenuated Type I Vaccine Strain, Jason P. Gigley, Barbara A. Fox, David J. Bzik
Long-Term Immunity To Lethal Acute Or Chronic Type Ii Toxoplasma Gondii Infection Is Effectively Induced In Genetically Susceptible C57bl/6 Mice By Immunization With An Attenuated Type I Vaccine Strain, Jason P. Gigley, Barbara A. Fox, David J. Bzik
Dartmouth Scholarship
C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized …
Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti
Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti
Theses and Dissertations
Status epilepticus (SE) is a major clinical emergency resulting in continuous seizure activity that can cause brain injury and many molecular and pathophysiologic changes leading to neuronal plasticity. The neuronal plasticity following SE-induced brain injury can initiate epileptogenesis and lead to the ultimate expression of acquired epilepsy (AE), characterized clinically by spontaneous, recurrent seizures. Epileptogenesis is the process wherein healthy brain tissue is transformed into hyperexcitable neuronal networks that produce AE. Understanding these alterations induced by brain injury is an important clinical challenge and can lend insight into possible new therapeutic targets to halt the development of AE. Currently there …
Genes And Symptoms Of Schizophrenia: Modifiers, Networks, And Interactions In Complex Disease, Sarah Bergen
Genes And Symptoms Of Schizophrenia: Modifiers, Networks, And Interactions In Complex Disease, Sarah Bergen
Theses and Dissertations
Understanding the genetic foundations of schizophrenia and the resultant symptom manifestations is an important step as we work toward development of new prevention and treatment strategies. This work has sought better understanding of this disease through use of three subject cohorts and two studies using simulated data exploring features of complex disease. First, we probed the symptoms of schizophrenia in subjects of African and European ancestry drawn from the Genetic Association Information Network (GAIN) schizophrenia study and found significant differences between groups, particularly in affective symptoms. The genetic basis of symptom variation was then explored in a selection of candidate …
N-Glycosylation Status Of E-Cadherin Controls Cytoskeletal Dynamics Through The Organization Of Distinct Β-Catenin- And Γ-Catenin-Containing Ajs., Basem T Jamal, Mihai Nita-Lazar, Zhennan Gao, Bakr Amin, Janice Walker, Maria A Kukuruzinska
N-Glycosylation Status Of E-Cadherin Controls Cytoskeletal Dynamics Through The Organization Of Distinct Β-Catenin- And Γ-Catenin-Containing Ajs., Basem T Jamal, Mihai Nita-Lazar, Zhennan Gao, Bakr Amin, Janice Walker, Maria A Kukuruzinska
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
N-glycosylation of E-cadherin has been shown to inhibit cell-cell adhesion. Specifically, our recent studies have provided evidence that the reduction of E-cadherin N-glycosylation promoted the recruitment of stabilizing components, vinculin and serine/threonine protein phosphatase 2A (PP2A), to adherens junctions (AJs) and enhanced the association of AJs with the actin cytoskeleton. Here, we examined the details of how N-glycosylation of E-cadherin affected the molecular organization of AJs and their cytoskeletal interactions. Using the hypoglycosylated E-cadherin variant, V13, we show that V13/β-catenin complexes preferentially interacted with PP2A and with the microtubule motor protein dynein. This correlated with dephosphorylation of the microtubule-associated protein …
The Otto Aufranc Award Identification Of A 4 Mb Region On Chromosome 17q21 Linked To Developmental Dysplasia Of The Hip In One 18-Member, Multigeneration Family, George Feldman, Chelsea Dalsey, Kasia Fertala, David Azimi, Paolo Fortina, Marcella Devoto, Maurizio Pacifici, Javad Parvizi
The Otto Aufranc Award Identification Of A 4 Mb Region On Chromosome 17q21 Linked To Developmental Dysplasia Of The Hip In One 18-Member, Multigeneration Family, George Feldman, Chelsea Dalsey, Kasia Fertala, David Azimi, Paolo Fortina, Marcella Devoto, Maurizio Pacifici, Javad Parvizi
Department of Orthopaedic Surgery Faculty Papers
Developmental dysplasia of the hip (DDH) is a disabling condition of the hip that, depending on geography, can afflict between 20-80% of patients with end-stage arthritis of the hip. Despite its prevalence, the etiology of this disease remains unknown. DDH is a complex disorder with both environmental and genetic causes.. Based on the literature, the candidate genes for the disease are HOXB9, collagen type I α1, and DLX 3. The purpose of our study was to map and characterize the gene or genes responsible for this disorder by family linkage analysis. We recruited one 18-member, multigeneration affected family to provide …
Adapting To Dynamic Stimulus-Response Values: Differential Contributions Of Inferior Frontal, Dorsomedial, And Dorsolateral Regions Of Prefrontal Cortex To Decision Making., Derek G V Mitchell, Qian Luo, Shelley B Avny, Tomasz Kasprzycki, Karanvir Gupta, Gang Chen, Elizabeth C Finger, R James R Blair
Adapting To Dynamic Stimulus-Response Values: Differential Contributions Of Inferior Frontal, Dorsomedial, And Dorsolateral Regions Of Prefrontal Cortex To Decision Making., Derek G V Mitchell, Qian Luo, Shelley B Avny, Tomasz Kasprzycki, Karanvir Gupta, Gang Chen, Elizabeth C Finger, R James R Blair
Brain and Mind Institute Researchers' Publications
Dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), and inferior frontal gyrus (IFG) have all been implicated in resolving decision conflict whether this conflict is generated by having to select between responses of similar value or by making selections following a reversal in reinforcement contingencies. However, work distinguishing their individual functional contributions remains preliminary. We used functional magnetic resonance imaging to delineate the functional role of these systems with regard to both forms of decision conflict. Within dmPFC and dlPFC, blood oxygen level-dependent responses increased in response to decision conflict regardless of whether the conflict occurred in the context of …
An Examination Of Chimpanzee Use In Human Cancer Research, Jarrod Bailey
An Examination Of Chimpanzee Use In Human Cancer Research, Jarrod Bailey
Laboratory Experiments Collection
Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human …
Effects Of Genistein Following Fractionated Lung Irradiation In Mice., Andrea E Para, Andrea Bezjak, Ivan W T Yeung, Jacob Van Dyk, Richard P Hill
Effects Of Genistein Following Fractionated Lung Irradiation In Mice., Andrea E Para, Andrea Bezjak, Ivan W T Yeung, Jacob Van Dyk, Richard P Hill
Oncology Publications
BACKGROUND AND PURPOSE: This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response.
MATERIAL AND METHODS: C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet ( approximately 10mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of …
Overexpression Of Mcl-1 Attenuates Liver Injury And Fibrosis In The Bile Duct-Ligated Mouse., Alisan Kahraman, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Fernando J. Barreyro, Maria E. Guicciardi, Yuko Akazawa, Karen Braley, Ruth W. Craig, Gregory J. Gores
Overexpression Of Mcl-1 Attenuates Liver Injury And Fibrosis In The Bile Duct-Ligated Mouse., Alisan Kahraman, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Fernando J. Barreyro, Maria E. Guicciardi, Yuko Akazawa, Karen Braley, Ruth W. Craig, Gregory J. Gores
Journal Articles: Biochemistry & Molecular Biology
Hepatocyte apoptosis contributes to liver injury and fibrosis after cholestatic injury. Our aim was to ascertain if the anti-apoptotic protein Mcl-1 alters liver injury or fibrosis in the bile duct-ligated mouse. Markers of apoptosis and fibrosis were compared in wild-type and transgenic mice expressing human Mcl-1 after bile duct ligation. Compared to hMcl-1 transgenic animals, ligated wild-type mice displayed a significant increase in TUNEL-positive cells and in caspase 3/7-positive hepatocytes. Consistent with apoptotic injury, the pro-apoptotic protein Bak underwent a conformational change to an activated form upon cholestatic injury, a change mitigated by hMcl-1 overexpression. Likewise, liver histology, number of …
Neurodevelopmental Outcome & Mr Spectroscopy Of Therapeutic Hypothermia After Pediatric Drowning, Sharon Mieras Perugini
Neurodevelopmental Outcome & Mr Spectroscopy Of Therapeutic Hypothermia After Pediatric Drowning, Sharon Mieras Perugini
Loma Linda University Electronic Theses, Dissertations & Projects
Despite advances in medical treatment and technology, outcome following pediatric drowning can vary widely from mild to severe impairments and death. Prognosis is often difficult to predict given a number of contributing factors. As such, this study examined the relationship between clinical indicators including submersion duration, initial GCS and PRISM scores, and waking time with outcome as well as metabolite ratios based on magnetic resonance spectroscopy. Research stemming from the area of cardiac arrest as well as anecdotal case study reports of cold water drownings suggests that lowering the body temperature may be helpful and protective. As such, the use …
Study Of The Four Factor Theory Of Women’S Sexual Function, Julie M. Merrell
Study Of The Four Factor Theory Of Women’S Sexual Function, Julie M. Merrell
Loma Linda University Electronic Theses, Dissertations & Projects
Tiefer, Hall, and Tavris (2002) described factors comprising four categories of female sexual function. They suggested that unique factors need to be examined to understand sexual function in women. Socio-cultural, political, or economic factors, partner and relationship factors, psychological factors, and medical factors were described as aspects of women’s lives that can be the source of sexual dysfunction. In a previous study, Merrell (2007) utilized Tiefer et al’s (2002) four factor model of sexual functioning to examine female sexual functioning looking specifically at body shame, relationship satisfaction, positive and negative affect, sexual self-schema, and overall health. Based on the results …
Characterization Of Two Outer Membrane Proteins, Flgo And Flgp, That Influence Vibrio Cholerae Motility, Raquel M. Martinez, Madushini N. Dharmasena, Thomas J. Kirn, Ronald K. Taylor
Characterization Of Two Outer Membrane Proteins, Flgo And Flgp, That Influence Vibrio Cholerae Motility, Raquel M. Martinez, Madushini N. Dharmasena, Thomas J. Kirn, Ronald K. Taylor
Dartmouth Scholarship
Vibrio cholerae is highly motile by the action of a single polar flagellum. The loss of motility reduces the infectivity of V. cholerae, demonstrating that motility is an important virulence factor. FlrC is the sigma-54-dependent positive regulator of flagellar genes. Recently, the genes VC2206 (flgP) and VC2207 (flgO) were identified as being regulated by FlrC via a microarray analysis of an flrC mutant (D. C. Morris, F. Peng, J. R. Barker, and K. E. Klose, J. Bacteriol. 190:231-239, 2008). FlgP is reported to be an outer membrane lipoprotein required for motility that functions as a colonization factor. The study reported …
One Specialty’S Collaborative Approach To Competency-Based Curriculum Development, Diane Kittredge, Constance D. Baldwin, Miriam Bar-On, R. Franklin Trimm, Patricia S. Beach
One Specialty’S Collaborative Approach To Competency-Based Curriculum Development, Diane Kittredge, Constance D. Baldwin, Miriam Bar-On, R. Franklin Trimm, Patricia S. Beach
University Faculty and Staff Publications
The authors describe a seven-step consensus development process used to create the two most recent editions of the Academic Pediatric Association’s (APA’s) educational guidelines for pediatric residency. The 1996 (printed) and 2004 (online) editions of the guidelines were designed as flexible tools to help residency programs meet changing accreditation requirements by providing lists of goals and objectives and objective-based evaluation tools. The guidelines were developed in seven steps: (1) centralized national leadership combined with coordinated, disseminated authorship, (2) clear definition of targeted users and repeated assessment of their needs, (3) incorporation of up-to-date information from the literature and national experts, …