Digital Commons Network^™

Metabolism Of Brain Cortex And Cardiac Muscle Mitochondria In Hibernating 13-Lined Ground Squirrels Ictidomys Tridecemlineatus., Kirsten Gallagher, James F Staples

Biology Publications

During bouts of torpor, mitochondrial metabolism is known to be suppressed in the liver and skeletal muscle of hibernating mammals. This suppression is rapidly reversed during interbout euthermic (IBE) phases, when whole-animal metabolic rate and body temperature (T(b)) return spontaneously to euthermic levels. Such mitochondrial suppression may contribute significantly to energy savings, but the capacity of other tissues to suppress mitochondrial metabolism remains unclear. In this study we compared the metabolism of mitochondria from brain cortex and left ventricular cardiac muscle between animals sampled while torpid (stable T(b) near 5°C) and in IBE (stable T(b) near 37°C). Instead of isolating …

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 …

Neutrophils Control The Magnitude And Spread Of The Immune Response In A Thromboxane A2-Mediated Process, Chiao-Wen Yang, Emil R. Unanue

Open Access Publications

Neutrophils are obligate cells entering lymph nodes shortly after immunization with protein antigens in adjuvants, starting during the first hour and continuing for several days in two distinct waves. Previously, we demonstrated the strong suppressive effects of neutrophils on CD4 T cell and B cell responses, using either neutrophil-depleting antibodies or genetically neutropenic mice. In this study, we find that neutrophils are the major cells controlling the spread of T cell responses to distal lymph nodes. Although in the presence of neutrophils, ∼75% of the response was restricted to the draining node, in their absence, most of the response was …

Characterization Of Induced Neural Progenitors From Skin Fibroblasts By A Novel Combination Of Defined Factors., Changhai Tian, Qiang Liu, Kangmu Ma, Yongxiang Wang, Qiang Chen, Randall Ambroz, David L. Klinkebiel, Yuju Li, Yunlong Huang, Jianqing Ding, Jie Wu, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

Recent reports have demonstrated that somatic cells can be directly converted to other differentiated cell types through ectopic expression of sets of transcription factors, directly avoiding the transition through a pluripotent state. Our previous experiments generated induced neural progenitor-like cells (iNPCs) by a novel combination of five transcription factors (Sox2, Brn2, TLX, Bmi1 and c-Myc). Here we demonstrated that the iNPCs not only possess NPC-specific marker genes, but also have qualities of primary brain-derived NPCs (WT-NPCs), including tripotent differentiation potential, mature neuron differentiation capability and synapse formation. Importantly, the mature neurons derived from iNPCs exhibit significant physiological properties, such as …

Evaluation Of Copper Concentration In Subclinical Cases Of White Muscle Disease And Its Relationship With Cardiac Troponin I, F. Ataollahi, M. Mohri, H.A. Seifi, Belinda Pingguan-Murphy, Wan Abu Bakar Wan Abas, Noor Azuan Abu Osman

Research Publications (2011 to 2015)

The present study aims to evaluate the serum level of copper (Cu) in lambs suffering from subclinical forms of white muscle disease (WMD) and its relationship with cardiac troponin I (cTn-I) as a novel biomarker of cardiovascular disorders. Ten milliliters of jugular blood were taken from 200 lambs less than one year old to measure serum concentrations of Cu, selenium (Se), and cTn-I. The subjects were divided into 2 groups, namely, the deficient group which included 36 lambs, and the control group which included 164 lambs according to the reference serum Se concentration (50 ng/mL). Serum Se levels in the …

Therapies For Neovascular Age-Related Macular Degeneration: Current Approaches And Pharmacologic Agents In Development., Mostafa Hanout, Daniel Ferraz, Mehreen Ansari, Natasha Maqsood, Saleema Kherani, Yasir J. Sepah, Nithya Rajagopalan, Mohamed Ibrahim, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is …

Genomics Of A Metamorphic Timing Qtl: Met1 Maps To A Unique Genomic Position And Regulates Morph And Species-Specific Patterns Of Brain Transcription, Robert B. Page, Meredith A. Boley, David K. Kump, Stephen R. Voss

Biology Faculty Publications

Very little is known about genetic factors that regulate life history transitions during ontogeny. Closely related tiger salamanders (Ambystoma species complex) show extreme variation in metamorphic timing, with some species foregoing metamorphosis altogether, an adaptive trait called paedomorphosis. Previous studies identified a major effect quantitative trait locus (met1) for metamorphic timing and expression of paedomorphosis in hybrid crosses between the biphasic Eastern tiger salamander (Ambystoma tigrinum tigrinum) and the paedomorphic Mexican axolotl (Ambystoma mexicanum). We used existing hybrid mapping panels and a newly created hybrid cross to map the met1 genomic region and …

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 …

Force Generation By Kinesin And Myosin Cytoskeletal Motor Proteins, F. Jon Kull, Sharyn A. Endow

Dartmouth Scholarship

Kinesins and myosins hydrolyze ATP, producing force that drives spindle assembly, vesicle transport and muscle contraction. How do motors do this? Here we discuss mechanisms of motor force transduction, based on their mechanochemical cycles and conformational changes observed in crystal structures. Distortion or twisting of the central β-sheet - proposed to trigger actin-induced Pi and ADP release by myosin, and microtubule-induced ADP release by kinesins - is shown in a movie depicting the transition between myosin ATP-like and nucleotide-free states. Structural changes in the switch I region form a tube that governs ATP hydrolysis and Pi release by the motors, …

Loss Of Mef2d Expression Inhibits Differentiation And Contributes To Oncogenesis In Rhabdomyosarcoma Cells., Meiling Zhang, Jamie Truscott, Judith Davie

Articles

BACKGROUND: Rhabdomyosarcoma (RMS) is a highly malignant pediatric cancer that is the most common form of soft tissue tumors in children. RMS cells have many features of skeletal muscle cells, yet do not differentiate. Thus, our studies have focused on the defects present in these cells that block myogenesis.

METHODS: Protein and RNA analysis identified the loss of MEF2D in RMS cells. MEF2D was expressed in RD and RH30 cells by transient transfection and selection of stable cell lines, respectively, to demonstrate the rescue of muscle differentiation observed. A combination of techniques such as proliferation assays, scratch assays and soft …

Ruminating On Ruminants: Goats And The People Who Raise Them In South Carolina, Brianna Dyan Farber

Theses and Dissertations

In South Carolina, many farmers and homesteaders have utilized goats as an adaptive and versatile resource and component of their diversified farming operations. This thesis addresses the experiences, motivations, difficulties, and successes of people raising goats in South Carolina, in the context of sustainable agricultural practice and landscapes. Goats cohabit insecure but promising ecological, political, economic, and sociocultural landscapes with humans and other nonhuman species. These relationships can undermine and support goats as belonging in South Carolina. My participants cannot simply raise goats as a purely economic choice because they create meaningful emotional relationships with their animals. Goats can become …

Tolerance Of Sponge Assemblages To Temperature Anomalies: Resilience And Proliferation Of Sponges Following The 1997-8 El-Niño Southern Oscillation., Francisco Kelmo, James J. Bell, Martin J. Attrill

School of Biological and Marine Sciences

Coral reefs across the world are under threat from a range of stressors, and while there has been considerable focus on the impacts of these stressors on corals, far less is known about their effect on other reef organisms. The 1997-8 El-Niño Southern Oscillation (ENSO) had notable and severe impacts on coral reefs worldwide, but not all reef organisms were negatively impacted by this large-scale event. Here we describe how the sponge fauna at Bahia, Brazil was influenced by the 1997-8 ENSO event. Sponge assemblages from three contrasting reef habitats (reef tops, walls and shallow banks) at four sites were …

Is The Reporting Timeliness Gap For Avian Flu And H1n1 Outbreaks In Global Health Surveillance Systems Associated With Country Transparency?, Feng-Jen Tsai, Eva Tseng, Chang-Chuan Chan, Hiko Tamashiro, Sandrine Motamed, André C Rougemont

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: This study aims to evaluate the length of time elapsed between reports of the same incidents related to avian flu and H1N1 outbreaks published by the WHO and ProMED-mail, the two major global health surveillance systems, before and after the amendment of the International Health Regulations in 2005 (IHR 2005) and to explore the association between country transparency and this timeliness gap.

METHODS: We recorded the initial release dates of each report related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the matching outbreak report from ProMED-mail, a non-governmental program for monitoring emerging …

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

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 …

The Eagleville Times,Volume 11, Issue 1, Debbie Ryan

Eagleville Times

No abstract provided.

Combination Therapy For Inflammation And Neurodegeneration In Multiple Sclerosis Rodent Model, Nicole Neva Marie Trager

MUSC Theses and Dissertations

Multiple sclerosis (MS) is a complex demyelinating CNS disease that involves both immunologic and neurodegenerative mechanisms of pathophysiology. MS is characterized by lymphocyte infiltration in the CNS resulting in extensive axonal neurodegenerative processes. The current therapies for MS act through either immunomodulatory or immunosuppressive mechanisms; none address both the immune and degenerative arms of the disease. The immunomodulatory agents are generally broad spectrum and non-specific immunosuppression and are associated with significant toxicities. Thus, novel therapies or therapeutic strategies are needed to fully combat both inflammatory and neurodegenerative events that define MS. The animal model experimental autoimmune encephalomyelitis (EAE) is used …

Tumor Necrosis Factor-Alpha Is Produced By Dying Retinal Neurons And Is Required For Müller Glia Proliferation During Zebrafish Retinal Regeneration, Craig M. Nelson, Kristin M. Ackerman, Patrick O'Hayer, Travis J. Bailey, Ryne A. Gorsuch, David R. Hyde

Biology

Intense light exposure causes photoreceptor apoptosis in dark-adapted adult albino zebrafish (Danio rerio). Subsequently, Müller glia increase expression of the Achaete-scute complex-like 1a (Ascl1a) and Signal transducer and activator of transcription 3 (Stat3) transcription factors and re-enter the cell cycle to yield undifferentiated neuronal progenitors that continue to proliferate, migrate to the outer nuclear layer, and differentiate into photoreceptors. A proteomic analysis of light-damaged retinal homogenates, which induced Müller glia proliferation when injected into an undamaged eye, revealed increased expression of tumor necrosis factor α (TNFα) signaling proteins relative to undamaged retinal homogenates. TNFα expression initially increased in apoptotic photoreceptors …

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 …

Mechanisms Of Wound Healing And Gastro Protective Effects Of Ethanol Leaf Extract Of Jasminum Sambac And Hemigraphis Colorata On Hcl/Ethanol-Induced Gastric Injury In Experimental Animals / Ahmed Salim Ahmed Al Rashdi, Ahmed Al Rashdi Ahmed Salim

Student Works (2010-2019)

Sprague Dawley rats weighing 225-250 g were used for evaluating wound healing and gastroprotective activities. The plant extracts of J.sambac and H.colorata were assessed in-vivo for toxicity study. Antioxidant properties of the crude extracts were determined using DPPH radical scavenging assay and total phenolic content. Β-sitosterol and octyl gallate compounds were isolated from J. sambac and H. Colorata petroleum ether crude extracts by CC, TLC and HPLC and were evaluated for their gastroprotective activities.Macroscopic finding showed that H.colorata and J.sambac significantly accelerated wound healing compared to vehicle. Post wounding tissues collected on day 10th for oxidative damage evaluation revealed significant …

Inhibition Of The Host Translation Shutoff Response By Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy, Kerstin Radtke, Luc English, Christiane Rondeau, David Leib

Dartmouth Scholarship

Macroautophagy is a cellular pathway that degrades intracellular pathogens and contributes to antigen presentation. Herpes simplex virus 1 (HSV-1) infection triggers both macroautophagy and an additional form of autophagy that uses the nuclear envelope as a source of membrane. The present study constitutes the first in-depth analysis of nuclear envelope-derived autophagy (NEDA). We established LC3a as a marker that allowed us to distinguish between NEDA and macroautophagy in both immunofluorescence and flow cytometry. NEDA was observed in many different cell types, indicating that it is a general response to HSV-1 infection. This autophagic pathway is known to depend on the …

Scfslimb Ubiquitin Ligase Suppresses Condensin Ii–Mediated Nuclear Reorganization By Degrading Cap-H2, Daniel W. Buster, Scott G. Daniel, Huy Q. Nguyen, Sarah L. Windler, Lara C. Skwarek, Maureen Peterson

Dartmouth Scholarship

Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCF(Slimb) ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCF(Slimb) function reorganized interphase chromosomes into dense, compact domains and disrupted …

Cis And Trans Regulatory Mechanisms Control Ap2-Mediated B Cell Receptor Endocytosis Via Select Tyrosine-Based Motifs., Kathleen Busman-Sahay, Lisa Drake, Anand Sitaram, Michael Marks, James R Drake

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding …

Chronic Ethanol Feeding Alters Mirna Expression Dynamics During Liver Regeneration., Rachael P Dippold, Rajanikanth Vadigepalli, Gregory E. Gonye, Biswanath Patra, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Adaptation to chronic ethanol (EtOH) treatment of rats results in a changed functional state of the liver and greatly inhibits its regenerative ability, which may contribute to the progression of alcoholic liver disease.

METHODS: In this study, we investigated the effect of chronic EtOH intake on hepatic microRNA (miRNA) expression in male Sprague-Dawley rats during the initial 24 hours of liver regeneration following 70% partial hepatectomy (PHx) using miRNA microarrays. miRNA expression during adaptation to EtOH was investigated using RT-qPCR. Nuclear factor kappa B (NFκB) binding at target miRNA promoters was investigated with chromatin immunoprecipitation.

RESULTS: Unsupervised clustering of …

Probiotic Pediococcus Acidilactici Modulates Both Localised Intestinal- And Peripheral-Immunity In Tilapia (Oreochromis Niloticus)., B. T. Standen, M. D. Rawling, S. J. Davies, M. Castex, A. Foey, G. Gioacchini, O. Carnevali, D. L. Merrifield

School of Biological and Marine Sciences

The application of probiotics in aquaculture has received concerted research efforts but the localised intestinal immunological response of fish to probiotic bacteria is poorly understood. Therefore, a study was conducted to evaluate the probiotic effect of Pediococcus acidilactici on Nile tilapia (Oreochromis niloticus) with specific emphasis on intestinal health and probiotic levels as well as system level responses such as growth performance, feed utilization and haemato-immunological parameters under non-challenged conditions. Fish (9.19 ± 0.04 g) were fed either a control diet or a P. acidilactici supplemented diet (at 2.81 × 10(6) CFU g(-)(1)) for six weeks. At the end of …

Candida Albicans Induces Arginine Biosynthetic Genes In Response To Host-Derived Reactive Oxygen Species, Claudia Jimenez-Lopez, John R. Collette, Kimberly M. Brothers, Kelly M. Shepardson, Robert A. Kramer

Dartmouth Scholarship

The interaction of Candida albicans with phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is …

System Analysis Of Spatial Frequency Domain Imaging For Quantitative Mapping Of Surgically Resected Breast Tissues, Ashley M. Laughney, Venkataramanan Krishnaswamy, Tyler B. Rice, David J. Cuccia

Dartmouth Scholarship

No abstract provided.

Nitric Oxide Affects Short-Term Olfactory Memory In The Antennal Lobe Of Manduca Sexta, S. L. Gage, K. C. Daly, A. Nighorn

Faculty & Staff Scholarship

No abstract provided.

Hdl And Glut1 Inhibition Reverse A Hypermetabolic State In Mouse Models Of Myeloproliferative Disorders, Emmanuel L. Gautier, Marit Westerterp, Neha Bhagwat, Serge Cremers, Alan Shih, Omar Abdel-Wahab, Dieter Lütjohann, Gwendalyn J. Randolph, Ross L. Levine, Alan R. Tall, Laurent Yvan-Charvet

Open Access Publications

A high metabolic rate in myeloproliferative disorders is a common complication of neoplasms, but the underlying mechanisms are incompletely understood. Using three different mouse models of myeloproliferative disorders, including mice with defective cholesterol efflux pathways and two models based on expression of human leukemia disease alleles, we uncovered a mechanism by which proliferating and inflammatory myeloid cells take up and oxidize glucose during the feeding period, contributing to energy dissipation and subsequent loss of adipose mass. In vivo, lentiviral inhibition of Glut1 by shRNA prevented myeloproliferation and adipose tissue loss in mice with defective cholesterol efflux pathway in leukocytes. Thus, …

Cd2ap Links Cortactin And Capping Protein At The Cell Periphery To Facilitate Formation Of Lamellipodia, Jianping Zhao, Serawit Bruck, Saso Cemerski, Lei Zhang, Boyd Butler, Adish Dani, John A. Cooper, Andrey S. Shaw

Open Access Publications

Understanding the physiology of complex relationships between components of signaling pathways and the actin cytoskeleton is an important challenge. CD2AP is a membrane scaffold protein implicated in a variety of physiological and disease processes. The physiological function of CD2AP is unclear, but its biochemical interactions suggest that it has a role in dynamic actin assembly. Here, we report that CD2AP functions to facilitate the recruitment of actin capping protein (CP) to the Src kinase substrate, cortactin, at the cell periphery, and that this is necessary for formation of the short branched filaments that characterize lamellipodium formation and are required for …