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Reinforcing Effects Of Compounds Lacking Intrinsic Efficacy At Α1 Subunit-Containing Gabaa Receptor Subtypes In Midazolam- But Not Cocaine-Experienced Rhesus Monkeys., Nina M Shinday, Eileen K Sawyer, Bradford D Fischer, Donna M Platt, Stephanie C Licata, John R Atack, Gerard R Dawson, David S Reynolds, James K Rowlett May 2013

Reinforcing Effects Of Compounds Lacking Intrinsic Efficacy At Α1 Subunit-Containing Gabaa Receptor Subtypes In Midazolam- But Not Cocaine-Experienced Rhesus Monkeys., Nina M Shinday, Eileen K Sawyer, Bradford D Fischer, Donna M Platt, Stephanie C Licata, John R Atack, Gerard R Dawson, David S Reynolds, James K Rowlett

Cooper Medical School of Rowan University Departmental Research

Benzodiazepines are prescribed widely but their utility is limited by unwanted side effects, including abuse potential. The mechanisms underlying the abuse-related effects of benzodiazepines are not well understood, although α1 subunit-containing GABAA receptors have been proposed to have a critical role. Here, we examine the reinforcing effects of several compounds that vary with respect to intrinsic efficacy at α2, α3, and α5 subunit-containing GABAA receptors but lack efficacy at α1 subunit-containing GABAA receptors ('α1-sparing compounds'): MRK-623 (functional selectivity for α2/α3 subunit-containing receptors), TPA023B (functional selectivity for α2/α3/α5 subunit-containing receptors), and TP003 (functional selectivity for α3 subunit-containing receptors). The reinforcing effects …


Completely Steroid-Free Immunosuppression In Liver Transplantation: A Randomized Study., Carlo B. Ramirez, Md, Cataldo Doria, Md, Phd, Adam M. Frank, Md, Stephen T. Armenti, Ignazio R. Marino, Md May 2013

Completely Steroid-Free Immunosuppression In Liver Transplantation: A Randomized Study., Carlo B. Ramirez, Md, Cataldo Doria, Md, Phd, Adam M. Frank, Md, Stephen T. Armenti, Ignazio R. Marino, Md

Department of Surgery Faculty Papers

INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT.

METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and …


Svsxp: A Strongylus Vulgaris Antigen With Potential For Prepatent Diagnosis, Ulla V. Andersen, Daniel K. Howe, Sriveny Dangoudoubiyam, Nils Toft, Craig R. Reinemeyer, Eugene T. Lyons, Susanne N. Olsen, Jesper Monrad, Peter Nejsum, Martin K. Nielsen Apr 2013

Svsxp: A Strongylus Vulgaris Antigen With Potential For Prepatent Diagnosis, Ulla V. Andersen, Daniel K. Howe, Sriveny Dangoudoubiyam, Nils Toft, Craig R. Reinemeyer, Eugene T. Lyons, Susanne N. Olsen, Jesper Monrad, Peter Nejsum, Martin K. Nielsen

Veterinary Science Faculty Publications

BACKGROUND: Strongyle parasites are ubiquitous in grazing horses. Strongylus vulgaris, the most pathogenic of the large strongyles, is known for its extensive migration in the mesenteric arterial system. The lifecycle of S. vulgaris is characterised by a long prepatent period where the migrating larvae are virtually undetectable as there currently is no test available for diagnosing prepatent S. vulgaris infection. Presence of S. vulgaris larvae in the arterial system causes endarteritis and thrombosis with a risk of non-strangulating intestinal infarctions. Emergence of anthelmintic resistance among cyathostomins has led to recommendations of reduced treatment intensity by targeting horses that exceed a …


Geographic Variation In Chin Shape Challenges The Universal Facial Attractiveness Hypothesis, Zaneta M. Thayer, Seth D. Dobson Apr 2013

Geographic Variation In Chin Shape Challenges The Universal Facial Attractiveness Hypothesis, Zaneta M. Thayer, Seth D. Dobson

Dartmouth Scholarship

The universal facial attractiveness (UFA) hypothesis proposes that some facial features are universally preferred because they are reliable signals of mate quality. The primary evidence for this hypothesis comes from cross-cultural studies of perceived attractiveness. However, these studies do not directly address patterns of morphological variation at the population level. An unanswered question is therefore: Are universally preferred facial phenotypes geographically invariant, as the UFA hypothesis implies? The purpose of our study is to evaluate this often overlooked aspect of the UFA hypothesis by examining patterns of geographic variation in chin shape. We collected symphyseal outlines from 180 recent human …


Warm Springs, Early Lay Dates, And Double Brooding In A North American Migratory Songbird, The Black-Throated Blue Warbler, Andrea K. Townsend, T. Scott Sillett, Nina K. Lany, Sara A. Kaiser, Nicholas L. Rodenhouse, Michael S. Webster, Richard T. Holmes Apr 2013

Warm Springs, Early Lay Dates, And Double Brooding In A North American Migratory Songbird, The Black-Throated Blue Warbler, Andrea K. Townsend, T. Scott Sillett, Nina K. Lany, Sara A. Kaiser, Nicholas L. Rodenhouse, Michael S. Webster, Richard T. Holmes

Dartmouth Scholarship

Numerous studies have correlated the advancement of lay date in birds with warming climate trends, yet the fitness effects associated with this phenological response have been examined in only a small number of species. Most of these species–primarily insectivorous cavity nesters in Europe–exhibit fitness declines associated with increasing asynchrony with prey. Here, we use 25 years of demographic data, collected from 1986 to 2010, to examine the effects of spring temperature on breeding initiation date, double brooding, and annual fecundity in a Nearctic - Neotropical migratory songbird, the black-throated blue warbler (Setophaga caerulescens). Data were collected from birds breeding at …


Altered Network Timing In The Ca3-Ca1 Circuit Of Hippocampal Slices From Aged Mice., Daniel J Kanak, Gregory M Rose, Hitten P Zaveri, Peter R Patrylo Apr 2013

Altered Network Timing In The Ca3-Ca1 Circuit Of Hippocampal Slices From Aged Mice., Daniel J Kanak, Gregory M Rose, Hitten P Zaveri, Peter R Patrylo

Articles

Network patterns are believed to provide unique temporal contexts for coordinating neuronal activity within and across different regions of the brain. Some of the characteristics of network patterns modeled in vitro are altered in the CA3 or CA1 subregions of hippocampal slices from aged mice. CA3-CA1 network interactions have not been examined previously. We used slices from aged and adult mice to model spontaneous sharp wave ripples and carbachol-induced gamma oscillations, and compared measures of CA3-CA1 network timing between age groups. Coherent sharp wave ripples and gamma oscillations were evident in the CA3-CA1 circuit in both age groups, but the …


Biodistribution And Biopersistence Of Ceria Engineered Nanomaterials: Size Dependence, Robert A. Yokel, Michael T. Tseng, Mo Dan, Jason M. Unrine, Uschi M. Graham, Peng Wu, Eric A. Grulke Apr 2013

Biodistribution And Biopersistence Of Ceria Engineered Nanomaterials: Size Dependence, Robert A. Yokel, Michael T. Tseng, Mo Dan, Jason M. Unrine, Uschi M. Graham, Peng Wu, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

The aims were to determine the biodistribution, translocation, and persistence of nanoceria in the brain and selected peripheral organs. Nanoceria is being studied as an anti-oxidant therapeutic. Five, 15, 30, or 55 nm ceria was iv infused into rats which were terminated 1, 20, or 720 h later. Cerium was determined in blood, brain, liver, and spleen. Liver and spleen contained a large percentage of the dose, from which there was no significant clearance over 720 h, associated with adverse changes. Very little nanoceria entered brain parenchyma. The results suggest brain delivery of nanoceria will be a challenge.

FROM THE …


Pick1 And Ica69 Control Insulin Granule Trafficking And Their Deficiencies Lead To Impaired Glucose Tolerance, Mian Cao, Zhuo Mao, Chuen Kam, Nan (Tori) Xiao, Xiaoxing Cao, Chong Shen, Kenneth K. Y. Cheng, Aimin Xu, Kwong-Man Lee, Liwen Jiang, Jun Xia Apr 2013

Pick1 And Ica69 Control Insulin Granule Trafficking And Their Deficiencies Lead To Impaired Glucose Tolerance, Mian Cao, Zhuo Mao, Chuen Kam, Nan (Tori) Xiao, Xiaoxing Cao, Chong Shen, Kenneth K. Y. Cheng, Aimin Xu, Kwong-Man Lee, Liwen Jiang, Jun Xia

All Dugoni School of Dentistry Faculty Articles

Diabetes is a metabolic disorder characterized by hyperglycemia. Insulin, which is secreted by pancreatic beta cells, is recognized as the critical regulator of blood glucose, but the molecular machinery responsible for insulin trafficking remains poorly defined. In particular, the roles of cytosolic factors that govern the formation and maturation of insulin granules are unclear. Here we report that PICK1 and ICA69, two cytosolic lipid-binding proteins, formed heteromeric BAR-domain complexes that associated with insulin granules at different stages of their maturation. PICK1-ICA69 heteromeric complexes associated with immature secretory granules near the trans-Golgi network (TGN). A brief treatment of Brefeldin A, which …


Intra-Tumoral Heterogeneity In Metastatic Potential And Survival Signaling Between Iso-Clonal Hct116 And Hct116b Human Colon Carcinoma Cell Lines., Sanjib Chowdhury, Melanie Ongchin, Elizabeth Sharratt, Ivan Dominguez, J. Wang, Michael G. Brattain, Ashwani Rajput Apr 2013

Intra-Tumoral Heterogeneity In Metastatic Potential And Survival Signaling Between Iso-Clonal Hct116 And Hct116b Human Colon Carcinoma Cell Lines., Sanjib Chowdhury, Melanie Ongchin, Elizabeth Sharratt, Ivan Dominguez, J. Wang, Michael G. Brattain, Ashwani Rajput

Journal Articles: Eppley Institute

BACKGROUND: Colorectal cancer (CRC) metastasis is a leading cause of cancer-related deaths in the United States. The molecular mechanisms underlying this complex, multi-step pathway are yet to be completely elucidated. Recent reports have stressed the importance of intra-tumoral heterogeneity in the development of a metastatic phenotype. The purpose of this study was to characterize the intra-tumoral phenotypic heterogeneity between two iso-clonal human colon cancer sublines HCT116 and HCT116b on their ability to undergo metastatic colonization and survive under growth factor deprivation stress (GFDS).

MATERIALS AND METHODS: HCT116 and HCT116b cells were transfected with green fluorescence protein and subcutaneously injected into …


Marked Improvement Of Cytotoxic Effects Induced By Docetaxel On Highly Metastatic And Androgen-Independent Prostate Cancer Cells By Downregulating Macrophage Inhibitory Cytokine-1., M Mimeault, Sonny L. Johansson, Surinder K. Batra Mar 2013

Marked Improvement Of Cytotoxic Effects Induced By Docetaxel On Highly Metastatic And Androgen-Independent Prostate Cancer Cells By Downregulating Macrophage Inhibitory Cytokine-1., M Mimeault, Sonny L. Johansson, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Overexpression of macrophage inhibitory cytokine-1 (MIC-1) frequently occurs during the progression of prostate cancer (PC) to androgen-independent (AI) and metastatic disease states and is associated with a poor outcome of patients.

METHODS: The gain- and loss-of-function analyses of MIC-1 were performed to establish its implications for aggressive and chemoresistant phenotypes of metastatic and AI PC cells and the benefit of its downregulation for reversing docetaxel resistance.

RESULTS: The results have indicated that an enhanced level of secreted MIC-1 protein in PC3 cells is associated with their acquisition of epithelial-mesenchymal transition features and higher invasive capacity and docetaxel resistance. Importantly, …


Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang Mar 2013

Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

Recent clinical observations demonstrate adiponectin (APN), an adipocytokine with potent cardioprotective actions, is significantly reduced following myocardial ischemia/reperfusion (MI/R). However, mechanisms responsible for MI/R-induced hypoadiponectinemia remain incompletely understood. Adult male mice were subjected to 30-min MI followed by varying reperfusion periods. Adipocyte APN mRNA and protein expression and plasma APN and TNFα concentrations were determined. APN expression/production began to decline 3 h after reperfusion (reaching nadir 12 h after reperfusion), returning to control levels 7 days after reperfusion. Plasma TNFα levels began to increase 1 h after reperfusion, peaking at 3 h and returning to control levels 24 h after …


Effects Of Aging On Apoptosis Gene Expression In Oral Mucosal Tissues, Octavio A. Gonzalez, Michael John Novak, Sreenatha S. Kirakodu, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Jeffrey L. Ebersole Mar 2013

Effects Of Aging On Apoptosis Gene Expression In Oral Mucosal Tissues, Octavio A. Gonzalez, Michael John Novak, Sreenatha S. Kirakodu, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = …


Population Impacts Of Wolbachia On Aedes Albopictus, James W. Mains, Corey L. Brelsfoard, Philip R. Crain, Yunxin Huang, Stephen L. Dobson Mar 2013

Population Impacts Of Wolbachia On Aedes Albopictus, James W. Mains, Corey L. Brelsfoard, Philip R. Crain, Yunxin Huang, Stephen L. Dobson

Entomology Faculty Publications

Prior studies have demonstrated that Wolbachia, a commonly occurring bacterium capable of manipulating host reproduction, can affect life history traits in insect hosts, which in turn can have population-level effects. Effects on hosts at the individual level are predicted to impact population dynamics, but the latter has not been examined empirically. Here, we describe a biological model system based on Aedes albopictus (Asian tiger mosquito) that allows for measurement of population dynamics, which has not been accomplished in prior field trials or laboratory designs. The results demonstrate the studied populations to be robust and allow for persistent, closed populations with …


An Acacb Variant Implicated In Diabetic Nephropathy Associates With Body Mass Index And Gene Expression In Obese Subjects, Lijun Ma, Mariana Murea, James A. Snipes, Alejandra Marinelarena, Jacqueline Krüger, Pamela J. Hicks, Kurt A. Langberg, Meredith A. Bostrom, Jessica N. Cooke, Daisuke Suzuki, Tetsuya Babazono, Takashi Uzu, Sydney C. W. Tang, Ashis K. Mondal, Neeraj K. Sharma, Sayuko Kobes, Peter A. Antinozzi, Matthew Davis, Swapan K. Das, Neda Rasouli, Philip A. Kern, Nathan J. Shores, Lawrence L. Rudel, Matthias Blüher, Michael Stumvoll, Donald W. Bowden, Shiro Maeda, John S. Parks, Peter Kovacs, Robert L. Hanson, Leslie J. Baier, Steven C. Elbein, Barry I. Freedman Feb 2013

An Acacb Variant Implicated In Diabetic Nephropathy Associates With Body Mass Index And Gene Expression In Obese Subjects, Lijun Ma, Mariana Murea, James A. Snipes, Alejandra Marinelarena, Jacqueline Krüger, Pamela J. Hicks, Kurt A. Langberg, Meredith A. Bostrom, Jessica N. Cooke, Daisuke Suzuki, Tetsuya Babazono, Takashi Uzu, Sydney C. W. Tang, Ashis K. Mondal, Neeraj K. Sharma, Sayuko Kobes, Peter A. Antinozzi, Matthew Davis, Swapan K. Das, Neda Rasouli, Philip A. Kern, Nathan J. Shores, Lawrence L. Rudel, Matthias Blüher, Michael Stumvoll, Donald W. Bowden, Shiro Maeda, John S. Parks, Peter Kovacs, Robert L. Hanson, Leslie J. Baier, Steven C. Elbein, Barry I. Freedman

Internal Medicine Faculty Publications

Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n …


Evolutionarily Novel Functional Networks In The Human Brain?, Dante Mantini, Maurizio Corbetta, Gian Luca Romani, Guy A. Orban, Wim Vanduffel Feb 2013

Evolutionarily Novel Functional Networks In The Human Brain?, Dante Mantini, Maurizio Corbetta, Gian Luca Romani, Guy A. Orban, Wim Vanduffel

Open Access Publications

Primate evolution has been accompanied by complex reorganizations in brain anatomy and function. Little is known, however, about the relationship between anatomical and functional changes induced through primate evolution. Using functional magnetic resonance imaging, we assessed spatial and temporal correspondences of cortical networks in humans and monkeys. We provided evidence for topologically and functionally correspondent networks in sensory-motor and attention regions. More specifically, we revealed a possible monkey equivalent of the human ventral attention network. For other human networks, such as the language and the default-mode networks, we detected topological correspondent networks in the monkey, but with different functional signatures. …


Stallion Sperm Transcriptome Comprises Functionally Coherent Coding And Regulatory Rnas As Revealed By Microarray Analysis And Rna-Seq., Pranab J. Das, Fiona M. Mccarthy, Monika Vishnoi, Nandina Paria, Cathy Gresham, Gang Li, Priyanka Kachroo, A. Kendrick Sudderth, Sheila Teague, Charles C. Love, Dickson D. Varner, Bhanu P. Chowdhary, Terje Raudsepp Feb 2013

Stallion Sperm Transcriptome Comprises Functionally Coherent Coding And Regulatory Rnas As Revealed By Microarray Analysis And Rna-Seq., Pranab J. Das, Fiona M. Mccarthy, Monika Vishnoi, Nandina Paria, Cathy Gresham, Gang Li, Priyanka Kachroo, A. Kendrick Sudderth, Sheila Teague, Charles C. Love, Dickson D. Varner, Bhanu P. Chowdhary, Terje Raudsepp

CVM Publications

Mature mammalian sperm contain a complex population of RNAs some of which might regulate spermatogenesis while others probably play a role in fertilization and early development. Due to this limited knowledge, the biological functions of sperm RNAs remain enigmatic. Here we report the first characterization of the global transcriptome of the sperm of fertile stallions. The findings improved understanding of the biological significance of sperm RNAs which in turn will allow the discovery of sperm-based biomarkers for stallion fertility. The stallion sperm transcriptome was interrogated by analyzing sperm and testes RNA on a 21,000-element equine whole-genome oligoarray and by RNA-seq. …


Associations Between Cadmium Exposure And Neurocognitive Test Scores In A Cross-Sectional Study Of Us Adults, Timothy Ciesielski, David C. Bellinger, Joel Schwartz, Russ Hauser, Robert O. Wright Feb 2013

Associations Between Cadmium Exposure And Neurocognitive Test Scores In A Cross-Sectional Study Of Us Adults, Timothy Ciesielski, David C. Bellinger, Joel Schwartz, Russ Hauser, Robert O. Wright

Dartmouth Scholarship

Background: Low-level environmental cadmium exposure and neurotoxicity has not been well studied in adults. Our goal was to evaluate associations between neurocognitive exam scores and a biomarker of cumulative cadmium exposure among adults in the Third National Health and Nutrition Examination Survey (NHANES III).

Methods: NHANES III is a nationally representative cross-sectional survey of the U.S. population conducted between 1988 and 1994. We analyzed data from a subset of participants, age 20–59, who participated in a computer-based neurocognitive evaluation. There were four outcome measures: the Simple Reaction Time Test (SRTT: visual motor speed), the Symbol Digit Substitution Test (SDST: attention/perception), …


Association Of Impaired Linear Growth And Worse Neurodevelopmental Outcome In Infants With Single Ventricle Physiology: A Report From The Pediatric Heart Network Infant Single Ventricle Trial., Chitra Ravishankar, Victor Zak, Ismee A. Williams, David C. Bellinger, J William Gaynor, Nancy S. Ghanayem, Catherine D. Krawczeski, Daniel J. Licht, Lynn Mahony, Jane W. Newburger, Victoria L. Pemberton, Richard V. Williams, Renee Sananes, Amanda L. Cook, Teresa Atz, Svetlana Khaikin, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali Feb 2013

Association Of Impaired Linear Growth And Worse Neurodevelopmental Outcome In Infants With Single Ventricle Physiology: A Report From The Pediatric Heart Network Infant Single Ventricle Trial., Chitra Ravishankar, Victor Zak, Ismee A. Williams, David C. Bellinger, J William Gaynor, Nancy S. Ghanayem, Catherine D. Krawczeski, Daniel J. Licht, Lynn Mahony, Jane W. Newburger, Victoria L. Pemberton, Richard V. Williams, Renee Sananes, Amanda L. Cook, Teresa Atz, Svetlana Khaikin, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To describe neurodevelopmental outcomes in infants with single ventricle (SV) physiology and determine factors associated with worse outcomes.

STUDY DESIGN: Neurodevelopmental outcomes for infants with SV enrolled in a multicenter drug trial were assessed at 14 months of age using the Bayley Scales of Infant Development-II. Multivariable regression analysis was used to identify factors associated with worse outcomes.

RESULTS: Neurodevelopmental testing was performed at 14 ± 1 months in 170/185 subjects in the trial. Hypoplastic left heart syndrome was present in 59% and 75% had undergone the Norwood operation. Mean Psychomotor Developmental Index (PDI) and mental developmental index (MDI) …


Properties Of Ribbon And Non-Ribbon Release From Rod Photoreceptors Revealed By Visualizing Individual Synaptic Vesicles., Minghui Chen, Matthew J. Van Hook, David Zenisek, Wallace B. Thoreson Jan 2013

Properties Of Ribbon And Non-Ribbon Release From Rod Photoreceptors Revealed By Visualizing Individual Synaptic Vesicles., Minghui Chen, Matthew J. Van Hook, David Zenisek, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

Vesicle release from rod photoreceptors is regulated by Ca(2+) entry through L-type channels located near synaptic ribbons. We characterized sites and kinetics of vesicle release in salamander rods by using total internal reflection fluorescence microscopy to visualize fusion of individual synaptic vesicles. A small number of vesicles were loaded by brief incubation with FM1-43 or a dextran-conjugated, pH-sensitive form of rhodamine, pHrodo. Labeled organelles matched the diffraction-limited size of fluorescent microspheres and disappeared rapidly during stimulation. Consistent with fusion, depolarization-evoked vesicle disappearance paralleled electrophysiological release kinetics and was blocked by inhibiting Ca(2+) influx. Rods maintained tonic release at resting membrane …


Tree Climbing And Human Evolution, Vivek V. Venkataraman, Thomas S. Kraft, Nathaniel J. Dominy Jan 2013

Tree Climbing And Human Evolution, Vivek V. Venkataraman, Thomas S. Kraft, Nathaniel J. Dominy

Dartmouth Scholarship

Paleoanthropologists have long argued—often contentiously—about the climbing abilities of early hominins and whether a foot adapted to terrestrial bipedalism constrained regular access to trees. However, some modern humans climb tall trees routinely in pursuit of honey, fruit, and game, often without the aid of tools or support systems. Mortality and morbidity associated with facultative arboreality is expected to favor behaviors and anatomies that facilitate safe and efficient climbing. Here we show that Twa hunter–gatherers use extraordinary ankle dorsiflexion (>45°) during climbing, similar to the degree observed in wild chimpanzees. Although we did not detect a skeletal signature of dorsiflexion …


Long-Term Upregulation Of Inflammation And Suppression Of Cell Proliferation In The Brain Of Adult Rats Exposed To Traumatic Brain Injury Using The Controlled Cortical Impact Model, Sandra A. Acosta, Naoki Tajiri, Kazutaka Shinozuka, Hiroto Ishikawa, Bethany Grimmig, David M. Diamond, Paul R. Sanberg, Paula C. Bickford, Yuji Kaneko, Cesario V. Borlongan Jan 2013

Long-Term Upregulation Of Inflammation And Suppression Of Cell Proliferation In The Brain Of Adult Rats Exposed To Traumatic Brain Injury Using The Controlled Cortical Impact Model, Sandra A. Acosta, Naoki Tajiri, Kazutaka Shinozuka, Hiroto Ishikawa, Bethany Grimmig, David M. Diamond, Paul R. Sanberg, Paula C. Bickford, Yuji Kaneko, Cesario V. Borlongan

Psychology Faculty Publications

The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal …


Coordinated Dynamic Gene Expression Changes In The Central Nucleus Of The Amygdala During Alcohol Withdrawal., Kate Freeman, Mary M. Staehle, Rajanikanth Vadigepalli, Gregory E Gonye, Babatunde A Ogunnaike, Jan B Hoek, James S Schwaber Jan 2013

Coordinated Dynamic Gene Expression Changes In The Central Nucleus Of The Amygdala During Alcohol Withdrawal., Kate Freeman, Mary M. Staehle, Rajanikanth Vadigepalli, Gregory E Gonye, Babatunde A Ogunnaike, Jan B Hoek, James S Schwaber

College of Science & Mathematics Departmental Research

BACKGROUND: Chronic alcohol use causes widespread changes in the cellular biology of the amygdala's central nucleus (CeA), a GABAergic center that integrates autonomic physiology with the emotional aspects of motivation and learning. While alcohol-induced neurochemical changes play a role in dependence and drinking behavior, little is known about the CeA's dynamic changes during withdrawal, a period of emotional and physiologic disturbance.

METHODS: We used a qRT-PCR platform to measure 139 transcripts in 92 rat CeA samples from control (N = 33), chronically alcohol exposed (N = 26), and withdrawn rats (t = 4, 8, 18, 32, and 48 hours; N …


Mice With Deficient Bk Channel Function Show Impaired Prepulse Inhibition And Spatial Learning, But Normal Working And Spatial Reference Memory., Marei Typlt, Magdalena Mirkowski, Erin Azzopardi, Lukas Ruettiger, Peter Ruth, Susanne Schmid Jan 2013

Mice With Deficient Bk Channel Function Show Impaired Prepulse Inhibition And Spatial Learning, But Normal Working And Spatial Reference Memory., Marei Typlt, Magdalena Mirkowski, Erin Azzopardi, Lukas Ruettiger, Peter Ruth, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this …


A Penile Spine/Vibrissa Enhancer Sequence Is Missing In Modern And Extinct Humans But Is Retained In Multiple Primates With Penile Spines And Sensory Vibrissae, Philip L. Reno, Cory Y Mclean, Jasmine E Hines, Terence D Capellini, Gill Bejerano, David M Kingsley Jan 2013

A Penile Spine/Vibrissa Enhancer Sequence Is Missing In Modern And Extinct Humans But Is Retained In Multiple Primates With Penile Spines And Sensory Vibrissae, Philip L. Reno, Cory Y Mclean, Jasmine E Hines, Terence D Capellini, Gill Bejerano, David M Kingsley

PCOM Scholarly Works

Previous studies show that humans have a large genomic deletion downstream of the Androgen Receptor gene that eliminates an ancestral mammalian regulatory enhancer that drives expression in developing penile spines and sensory vibrissae. Here we use a combination of large-scale sequence analysis and PCR amplification to demonstrate that the penile spine/vibrissa enhancer is missing in all humans surveyed and in the Neandertal and Denisovan genomes, but is present in DNA samples of chimpanzees and bonobos, as well as in multiple other great apes and primates that maintain some form of penile integumentary appendage and facial vibrissae. These results further strengthen …


A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors, Joseph P. Connor, Mihaela C. Cristea, Nancy L. Lewis, Lionel D. Lewis Jan 2013

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors, Joseph P. Connor, Mihaela C. Cristea, Nancy L. Lewis, Lionel D. Lewis

Dartmouth Scholarship

BackgroundHumanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.MethodsPhase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300mg/m2 on day 1), and escalating doses of h


A Newly Recorded Species In China, Ctenothrips Niger Kudô (Thysanoptera: Thripidae), And The First Description Of Its Male, Qing Ling Hu, Ji Nian Feng Jan 2013

A Newly Recorded Species In China, Ctenothrips Niger Kudô (Thysanoptera: Thripidae), And The First Description Of Its Male, Qing Ling Hu, Ji Nian Feng

Turkish Journal of Zoology

Ctenothrips niger Kudô, collected from Ailao Mountain, is a newly recorded species in China. Both males and females were collected. The male of the species is herein described and illustrated in detail for the first time.


Cattle-Related Injuries And Farm Management Practices On Kentucky Beef Cattle Farms, Steven R. Browning, Susan C. Westneat, Wayne T. Sanderson, Deborah B. Reed Jan 2013

Cattle-Related Injuries And Farm Management Practices On Kentucky Beef Cattle Farms, Steven R. Browning, Susan C. Westneat, Wayne T. Sanderson, Deborah B. Reed

Epidemiology and Environmental Health Faculty Publications

While working on farms with livestock increases the risk of injury among farm workers in comparison to other commodity farms, few studies have examined the role offarm management practices in association with the risk of cattle-related injury. We examined the farm management practices of Kentucky beef cattle farms in association with self-reported rates of cattle-related injuries among workers. We conducted a mail survey of a random sample of 2,500 members of the Kentucky Cattlemen's Association. Results from 1,149 farm operators who were currently raising beef cattle and provided complete survey response are reported. During the busy season, the principal operator …


The Evaluation Of Az66, An Optimized Sigma Receptor Antagonist, Against Methamphetamine-Induced Dopaminergic Neurotoxicity And Memory Impairment In Mice, Michael J. Seminerio, Rolf Hansen, Nidhi Kaushal, Han-Ting Zhang, Christopher R. Mccurdy, Rae R. Matsumoto Jan 2013

The Evaluation Of Az66, An Optimized Sigma Receptor Antagonist, Against Methamphetamine-Induced Dopaminergic Neurotoxicity And Memory Impairment In Mice, Michael J. Seminerio, Rolf Hansen, Nidhi Kaushal, Han-Ting Zhang, Christopher R. Mccurdy, Rae R. Matsumoto

Faculty & Staff Scholarship

Sigma (σ) receptors have recently been identified as potential targets for the development of novel therapeutics aimed at mitigating the effects of methamphetamine. Particularly, σ receptors are believed to mitigate some of the neurotoxic effects of methamphetamine through modulation of dopamine, dopamine transporters and body temperature. Furthermore, recent evidence suggests that targeting σ receptors may prevent cognitive impairments produced by methamphetamine. In the present study, an optimized σ receptor antagonist, AZ66, was evaluated against methamphetamine-induced neurotoxicity and cognitive dysfunction. AZ66 was found to be highly selective for σ receptors compared to 64 other sites tested. Pretreatment of male, Swiss Webster …


De Novo Orfs In Drosophila Are Important To Organismal Fitness And Evolved Rapidly From Previously Non-Coding Sequences, Josephine A. Reinhardt, Betty M. Wanjiru, Alicia T. Brant, Perot Saelao, David J. Begun, Corbin D. Jones Jan 2013

De Novo Orfs In Drosophila Are Important To Organismal Fitness And Evolved Rapidly From Previously Non-Coding Sequences, Josephine A. Reinhardt, Betty M. Wanjiru, Alicia T. Brant, Perot Saelao, David J. Begun, Corbin D. Jones

Biology

How non-coding DNA gives rise to new protein-coding genes (de novo genes) is not well understood. Recent work has revealed the origins and functions of a few de novo genes, but common principles governing the evolution or biological roles of these genes are unknown. To better define these principles, we performed a parallel analysis of the evolution and function of six putatively protein-coding de novo genes described in Drosophila melanogaster. Reconstruction of the transcriptional history of de novo genes shows that two de novo genes emerged from novel long non-coding RNAs that arose at least 5 MY prior to evolution …


Exploring Wellbeing In Older Male Farmers In Western Australia, Jessica L. Mckee Jan 2013

Exploring Wellbeing In Older Male Farmers In Western Australia, Jessica L. Mckee

Theses : Honours

In the context of an ageing population it has become increasingly important to identify the determinants of wellbeing in older adulthood. A review of the literature relevant to wellbeing and strengths relevant to older male farmers in Australia was conducted. This body of knowledge was identified to be sparse. Existing literature on farming primarily had a deficits focus, and only a small number of qualitative studies were specific to older male farmers. Four broad, overlapping areas representing the meaning of wellbeing were identified as potentially important: farming work; connectedness; the land; health and wellbeing. The inter-connected nature of farming life …