Digital Commons Network^™

Adult Neurogenesis In The Four-Striped Mice (Rhabdomys Pumilio), Olatunbosun O. Olaleye, Amadi O. Ihunwo

Brain and Mind Institute

In this study, we investigated non-captive four-striped mice (Rhabdomys pumilio) for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 (a marker for cell proliferation) and doublecortin (a marker for immature neurons) immunostaining confirmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of the hippocampus. No Ki-67 proliferating cells were observed in the striatum substantia nigra, amygdala, cerebral cortex or dorsal vagal complex. Doublecortin-immunoreactive cells were observed in …

The Incentive Amplifying Effects Of Nicotine Are Reduced By Selective And Non-Selective Dopamine Antagonists In Rats, Matthew I. Palmatier, Marissa R. Kellicut, A. Brianna Sheppard, Russell W. Brown, Donita L. Robinson

ETSU Faculty Works

Nicotine is a psychomotor stimulant with ‘reinforcement enhancing’ effects — the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate …

Phosphate And Acidosis Act Synergistically To Depress Peak Power In Rat Muscle Fibers, Cassandra R. Nelson, Edward P. Debold, Robert H. Fitts

Biomedical Sciences Faculty Research and Publications

Skeletal muscle fatigue is characterized by the buildup of H⁺ and inorganic phosphate (P_i), metabolites that are thought to cause fatigue by inhibiting muscle force, velocity, and power. While the individual effects of elevated H⁺ or P_i have been well characterized, the effects of simultaneously elevating the ions, as occurs during fatigue in vivo, are still poorly understood. To address this, we exposed slow and fast rat skinned muscle fibers to fatiguing levels of H⁺ (pH 6.2) and P_i (30 mM) and determined the effects on contractile properties. At 30°C, elevated P_{i …}

Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin

Dartmouth Scholarship

Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …

Ido2 In Immunomodulation And Autoimmune Disease., George C Prendergast, Richard Metz, Alexander J Muller, Lauren M F Merlo, Laura Mandik-Nayak

Department of Microbiology and Immunology Faculty Papers

IDO2 is a relative of IDO1 implicated in tryptophan catabolism and immune modulation but its specific contributions to normal physiology and pathophysiology are not known. Evolutionary genetic studies suggest that IDO2 has a unique function ancestral to IDO1. In mice, IDO2 gene deletion does not appreciably affect embryonic development or hematopoiesis, but it leads to defects in allergic or autoimmune responses and in the ability of IDO1 to influence the generation of T regulatory cells. Gene expression studies indicate that IDO2 is a basally and more narrowly expressed gene than IDO1 and that IDO2 is uniquely regulated by AhR, which …

Using Multi-Compartment Ensemble Modeling As An Investigative Tool Of Spatially Distributed Biophysical Balances: Application To Hippocampal Oriens-Lacunosum/Moleculare (O-Lm) Cellns, Vladislav Sekulic, J. Josh Lawrence, Frances K. Skinner

Biomedical and Pharmaceutical Sciences Faculty Publications

Multi-compartmental models of neurons provide insight into the complex, integrative properties of dendrites. Because it is not feasible to experimentally determine the exact density and kinetics of each channel type in every neuronal compartment, an essential goal in developing models is to help characterize these properties. To address biological variability inherent in a given neuronal type, there has been a shift away from using hand-tuned models towards using ensembles or populations of models. In collectively capturing a neuron’s output, ensemble modeling approaches uncover important conductance balances that control neuronal dynamics. However, conductances are never entirely known for a given neuron …

Characterization Of Severe Fever With Thrombocytopenia Syndrome In Rural Regions Of Zhejiang, China, Lei Zhang, Ling Ye, David M. Ojcius, Xiuyu Lou, Chengwei Wang, Cen Feng, Yi Sun, Zhongfa Wang, Shibo Li, Yanjun Zhang

All Dugoni School of Dentistry Faculty Articles

Severe fever with thrombocytopenia syndrome virus (SFTSV) infections have recently been found in rural regions of Zhejiang. A severe fever with thrombocytopenia syndrome (SFTS) surveillance and sero-epidemiological investigation was conducted in the districts with outbreaks. During the study period of 2011–2014, a total of 51 SFTSV infection cases were identified and the case fatality rate was 12% (6/51). Ninety two percent of the patients (47/51) were over 50 years of age, and 63% (32/51) of laboratory confirmed cases occurred from May to July. Nine percent (11/120) of the serum samples from local healthy people without symptoms were found to be …

Transcranial Magnetic Stimulation Of The Prefrontal Cortex In Awake Nonhuman Primates Evokes A Polysynaptic Neck Muscle Response That Reflects Oculomotor Activity At The Time Of Stimulation., Chao Gu, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Transcranial magnetic stimulation (TMS) has emerged as an important technique in cognitive neuroscience, permitting causal inferences about the contribution of a given brain area to behavior. Despite widespread use, exactly how TMS influences neural activity throughout an interconnected network, and how such influences ultimately change behavior, remain unclear. The oculomotor system of nonhuman primates (NHPs) offers a potential animal model to bridge this gap. Here, based on results suggesting that neck muscle activity provides a sensitive indicator of oculomotor activation, we show that single pulses of TMS over the frontal eye fields (FEFs) in awake NHPs evoked rapid (within ∼25 …

Latexin Sensitizes Leukemogenic Cells To Gamma-Irradiation-Induced Cell-Cycle Arrest And Cell Death Through Rps3 Pathway, Y. You, R. Wen, R. Pathak, A. Li, W. Li, D. St. Clair, M. Hauer-Jensen, D. Zhou, Ying Liang

Toxicology and Cancer Biology Faculty Publications

Leukemia is a leading cause of cancer death. Recently, the latexin (Lxn) gene was identified as a potential tumor suppressor in several types of solid tumors and lymphoma, and Lxn expression was found to be absent or downregulated in leukemic cells. Whether Lxn functions as a tumor suppressor in leukemia and what molecular and cellular mechanisms are involved are unknown. In this study, the myeloid leukemogenic FDC-P1 cell line was used as a model system and Lxn was ectopically expressed in these cells. Using the protein pull-down assay and mass spectrometry, ribosomal protein subunit 3 (Rps3) was identified as a …

Chasing The Dragon: A Case Of Inhaled Heroin Overdose Resulting In Stunned Myocardium, Neiman Ramjattan Do

Department of Medicine

No abstract provided.

Mmu-Mir-615-3p Regulates Lipoapoptosis By Inhibiting C/Ebp Homologous Protein., Yasuhiro Miyamoto, Amy S Mauer, Swarup Kumar, Justin L. Mott, Harmeet Malhi

Journal Articles: Biochemistry & Molecular Biology

Lipoapoptosis occurring due to an excess of saturated free fatty acids such as palmitate is a key pathogenic event in the initiation of nonalcoholic fatty liver disease. Palmitate loading of cells activates the endoplasmic reticulum stress response, including induction of the proapoptotic transcription factor C/EBP homologous protein (CHOP). Furthermore, the loss of microRNAs is implicated in regulating apoptosis under conditions of endoplasmic reticulum (ER) stress. The aim of this study was to identify specific microRNAs regulating CHOP expression during palmitate-induced ER stress. Five microRNAs were repressed under palmitate-induced endoplasmic reticulum stress conditions in hepatocyte cell lines (miR-92b-3p, miR-328-3p, miR-484, miR-574-5p, …

Assessment Of Anthelmintic Efficacy Of Mebendazole In School Children In Six Countries Where Soil-Transmitted Helminths Are Endemic, Bruno Levecke, Antonio Montresor, Marco Albonico, Shaali M. Ame, Jerzy M. Behnke, Jeffrey M. Bethony, +15 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND:

Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained …

Targeting The Small- And Intermediate Conductance Ca2+- Activated Potassium Channels: The Drug Binding Pocket At The Channel/Calmodulin Interface, Meng Cui, Guangrong Qin, Kunqian Yu, M. Scott Bowers, Miao Zhang

Pharmacy Faculty Articles and Research

The small- and intermediate-conductance Ca 2+ -activated potassium (SK/IK) channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca 2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca 2+ -binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been …

Smarter Vaccine Design Will Circumvent Regulatory T Cell-Mediated Evasion In Chronic Hiv And Hcv Infection, Leonard Moise, Frances Terry, Andres H. Gutierrez, Ryan Tassone, Phyllis Losikoff, Stephen H. Gregory, Chris Bailey-Kellogg

Dartmouth Scholarship

Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic infection is suppression of viral-specific effector CD4(+) and CD8(+) T cells by stimulating regulatory T cells (Tregs) educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a T cell receptor (TCR)-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses …

Hiv-1 Infection Of Macrophages Induces Retention Of Cholesterol Transporter Abca1 In The Endoplasmic Reticulum, Beda Brichacek, Christina Darwish, Anastas Popratiloff, Larisa Dubrovsky, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Therapeutic Hypothermia Following Cardiac Arrest, Cassandra Patrick

Nursing Student Class Projects (Formerly MSN)

According to the Sudden Cardiac Arrest Foundation (2014), each year, 424,000 people in the U.S. (more than 1,000/day) experience EMS-assessed out-of-hospital non-traumatic sudden cardiac arrest. This is roughly equivalent to the number of people who die from Alzheimers’ disease, assault with firearms, breast cancer, cervical cancer, colorectal cancer, diabetes, HIV, house fires, motor vehicle accidents, prostate cancer and suicides combined (Sudden Cardiac Arrest Foundation, 2014). It is estimated that the likelihood of surviving an out-of-hospital cardiac arrest (OHCA) to hospital discharge can be as low as 6% to 8% (Williams, Calder, Cocchi & Donnino, 2013). Additionally an estimated 200,000 hospitalized …

Ebola: Protecting Healthcare Workers, Martha Mccoy

Nursing Student Class Projects (Formerly MSN)

Ebola is a hemorrhagic disease that has been seen throughout Liberia, but because of international travel it is spreading. Gilsdorf, Morgan and Leitmeyer (2012) researched air travel and reported that, “In 2010, 5.04 billion passengers arrived and departed from 1318 airports worldwide… and travel to and from Africa almost doubled between 1995 and 2005.” (p.1471). In the last few months there have been cases of Ebola reported in Spain and the United States linked to travel. These are recent developments because as of July, 2014 the Center for Disease Control and Prevention (CDC) reported “to date there are no cases …

Ebola Pandemic, Lurajean Cravens

Nursing Student Class Projects (Formerly MSN)

Ebolavirus, or Ebola Virus Disease (EVD), is of the filovirus family causing hemorrhagic fever first discovered in the African country of Zaire in 1976 (Turner, 2014; Hampton, 2014) and has gained global concern and attention since the recent epidemic outbreak in West Africa. There are five known species of Ebola: Zaire, Sudan, Ivory Coast, Bundibugyo and Reston, based on the region of origination. The Zaire species has been identified as the strain responsible for the current outbreak in West Africa, and has spread to Liberia, Sierra Leone, Nigeria and Senegal (Centers for Disease Control and Prevention,2014; Gostin, Lucey & Phelan, …

Ebola, A Deadly Viral Disease Affecting The West African Country Of Sierra Leone, Unisa Seisay

Nursing Student Class Projects (Formerly MSN)

Presently, there has been an outbreak of Ebola Virus Disease (EVD) in the West African countries of Sierra Leone, Liberia, Nigeria, Senegal and Guinea. The outbreak was first discovered in Guinea in March 21, 2014 and has spread to the neighboring countries. This has resulted in a lot of fatalities and is now considered a global public health concern (WHO, 2014).

Marshall University Joan C. Edwards School Of Medicine, Professional Enhancement Newsletter, Fall 2014, Darshana Shah Ph.D

Professional Enhancement News (PEN)

Fall 2014, Volume 6, Number 2

Ct Perfusion Imaging As An Early Biomarker Of Differential Response To Stereotactic Radiosurgery In C6 Rat Gliomas, Timothy Pok Chi Yeung, Maher Kurdi, Yong Wang, Baraa Al-Khazraji, Laura Morrison, Lisa Hoffman, Dwayne Jackson, Cathie Crukley, Ting-Yim Lee, Glenn Bauman, Slav Yartsev

Medical Biophysics Publications

BACKGROUND: The therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT) perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model.

METHODS: Rats with orthotopic C6 glioma tumors received either mock irradiation (controls, N = 8) or stereotactic radiosurgery (N = 25, 12 Gy in one fraction) delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute …

Developmental Stress, Condition, And Birdsong: A Case Study In Song Sparrows., Kim L Schmidt, Elizabeth A Macdougall-Shackleton, Shawn P Kubli, Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

Sexual-selection theory posits that ornaments and displays can reflect a signaler's condition, which in turn is affected both by recent and developmental conditions. Moreover, developmental conditions can induce correlations between sexually selected and other traits if both types of traits exhibit developmental phenotypic plasticity in response to stressors. Thus, sexually selected traits may reflect recent and/or developmental characteristics of signalers. Here, we review data on the relationships between birdsong, a sexually selected trait, and developmental and current condition of birds from a long-term study of a population of song sparrows (Melospiza melodia). Field studies of free-living birds indicate that the …

Literary Research On Alport Syndrome, Shailendra Jain

Nursing Student Class Projects (Formerly MSN)

Alport syndrome is rare genetic disorder of the glomerulus in the kidneys that can be X-linked, Autosomal recessive, or Autosomal dominant in nature. Clinical manifestation includes hearing loss, hematuria, proteinuria, and hypertension (Cheungpasitporn, Kaewpoowat, Suksaranjit, Kittanamongkolchai, Srivali, Ungprasert, & Rangan, 2012). It is most common disease in males. A 24-hour urine specimen is usually obtained to check for proteinuria and elevated creatinine, which indicate acute renal failure (Cosgrove, 2012). A renal biopsy and ultrasounds is used to confirm the diagnosis of Alport Syndrome. Patients that are diagnosed with such disease require dialysis and referral to an ophthalmology and audiology. The …

Differences In Brainstem Level Encoding Of Am And Fm Signals In A Rat Model For Dyslexia, Stephen Anthony Chabot

Open Access Theses

Developmental dyslexia is a language learning disorder that affects a significant portion of the population. Many subjects who suffer from dyslexia show auditory processing deficits as children, some of which persist into adulthood, which impair their ability to learn one or more aspects of language. There is evidence that some types of training can correct the auditory processing deficits and bring the subject to a normal reading or speaking proficiency for their age group. One common rodent model for dyslexia is the cortical freeze lesion model. This model induces a lesion in the rat cortex similar to the microgyria present …

Ethanol-Induced Oxidant Stress Modulates Hepatic Autophagy And Proteasome Activity., Terrence M. Donohue, Paul G. Thomes

Journal Articles: Biochemistry & Molecular Biology

In this review, we describe research findings on the effects of alcohol exposure on two major catabolic systems in liver cells: the ubiquitin-proteasome system (UPS) and autophagy. These hydrolytic systems are not unique to liver cells; they exist in all eukaryotic tissues and cells. However, because the liver is the principal site of ethanol metabolism, it sustains the greatest damage from heavy drinking. Thus, the focus of this review is to specifically describe how ethanol oxidation modulates the activities of the UPS and autophagy and the mechanisms by which these changes contribute to the pathogenesis of alcohol-induced liver injury. Here, …

Genotypes Frequencies Of Rs9923231 And Rs7294 Snps In The Vkorci Gene Among Emiratis And Their Implications For Warfarin Dosage, Hayat Saad Al-Jaibeji

Theses

Warfarin is the most commonly used oral anticoagulant medication given as a prophylaxis and/or treatment of venous and arterial thromboembolic disorders. Warfarin doses vary up to 10-fold among patients due to pharmacokinetics, pharmacodynamics and pharmacogenomics factors. In addition, Warfarin has a low therapeutic index with the risk of developing serious side effects such as severe bleeding or failure of therapy. Therefore, the main challenge to achieve the therapeutic goal in warfarin treatment is estimating the appropriate dose for each patient. It is estimated that pharmacogenomics factors contribute to more than 60% of dose variability. The gene encoding for the target …

Effect Of Obesity And Exercise On The Expression Of The Novel Myokines, Myonectin And Fibronectin Type Iii Domain Containing 5, Jonathan M. Peterson, Ryan Mart, Cherie E. Bond

ETSU Faculty Works

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, …

Withaferin A Alone And In Combination With Cisplatin Suppresses Growth And Metastasis Of Ovarian Cancer By Targeting Putative Cancer Stem Cells., Sham S. Kakar, Mariusz Z. Ratajczak, Karen S. Powell, Mana Moghadamfalahi, Donald M. Miller, Surinder K. Batra, Sanjay K. Singh

Journal Articles: Biochemistry & Molecular Biology

Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly, carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately within few months of initial treatment, tumor relapse occurs because of platinum-resistance. This is attributed to chemo-resistance of cancer stem cells (CSCs). Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs. Treatment of nude mice bearing orthotopic ovarian tumors generated by injecting human ovarian epithelial cancer cell …

Inpp4b Suppresses Prostate Cancer Cell Invasion, Myles C. Hodgson, Elena I. Deryugina, Egla Suarez, Sandra M. Lopez, Dong Lin, Hui Xue, Ivan P. Gorlov

Dartmouth Scholarship

INPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease. We and others have previously shown that loss of INPP4B expression correlates with poor prognosis in multiple malignancies and with metastatic spread in prostate cancer.

We demonstrate that de novo expression of INPP4B in highly invasive human prostate carcinoma PC-3 cells suppresses their invasion both in vitro and in vivo. Using global gene expression analysis, we found that INPP4B regulates a number of genes associated with cell adhesion, the extracellular matrix, and the cytoskeleton. Importantly, de novo expressed INPP4B suppressed the proinflammatory chemokine …

Transformation Of Human Cathelicidin Ll-37 Into Selective, Stable, And Potent Antimicrobial Compounds., Guangshun Wang, Mark L. Hanke, Biswajit Mishra, Tamara Lushnikova, Cortney E. Heim, Vinai Chittezham Thomas, Kenneth W. Bayles, Tammy Kielian

Journal Articles: Pathology and Microbiology

This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli but not methicillin-resistant Staphylococcus aureus (MRSA). It possesses a unique nonclassic amphipathic structure with hydrophobic defects. By repairing the hydrophobic defects, the peptide (17BIPHE2) gained activity against the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species. In vitro, 17BIPHE2 could disrupt bacterial membranes and bind to DNA. In vivo, the peptide …