Digital Commons Network^™

Recent Experimental And Clinical Findings In The Skeleton Associated With Loss Of Estrogen Hormone Or Estrogen Receptor Activity, Eric P. Smith, Bonny Specker, Kenneth S Korach

Ethel Austin Martin Program Publications

Studies on rodent models and rare human disorders of estrogen production or response have revealed an increased complexity of the actions of estrogen on bone. ERalpha disruption in human males results in delayed epiphyseal maturation, tall stature, trabecular thinning, marked cortical thinning, genu valgum and significantly reduced cortical vBMD, but trabecular number is preserved and there is normal to increased periosteal expansion. Aromatase deficiency results overall in a similar phenotype, although less is known about skeletal architecture. Importantly, estrogen replacement in these individuals, even if provided late in the third decade, may normalize aBMD. Less certain is whether there is …

What Is Biomedical Informatics?, Elmer V Bernstam, Jack W Smith, Todd R Johnson

Faculty, Staff and Student Publications

Biomedical informatics lacks a clear and theoretically-grounded definition. Many proposed definitions focus on data, information, and knowledge, but do not provide an adequate definition of these terms. Leveraging insights from the philosophy of information, we define informatics as the science of information, where information is data plus meaning. Biomedical informatics is the science of information as applied to or studied in the context of biomedicine. Defining the object of study of informatics as data plus meaning clearly distinguishes the field from related fields, such as computer science, statistics and biomedicine, which have different objects of study. The emphasis on data …

Cardiomyocyte Pdgfr-Beta Signaling Is An Essential Component Of The Mouse Cardiac Response To Load-Induced Stress, Vishnu Chintalgattu, Di Ai, Robert R Langley, Jianhu Zhang, James A Bankson, Tiffany L Shih, Anilkumar K Reddy, Kevin R Coombes, Iyad N Daher, Shibani Pati, Shalin S Patel, Jennifer S Pocius, George E Taffet, L Maximillian Buja, Mark L Entman, Aarif Y Khakoo

Faculty, Staff and Student Publications

PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-beta expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to load-induced stress resulted …

Progressive Changes In Microglia And Macrophages In Spinal Cord And Peripheral Nerve In The Transgenic Rat Model Of Amyotrophic Lateral Sclerosis, David J. Graber, William F. Hickey, Brent T. Harris

Dartmouth Scholarship

The role of neuroinflammation in motor neuron death of amyotrophic lateral sclerosis (ALS) is unclear. The human mutant superoxide dismutase-1 (hmSOD1)-expressing murine transgenic model of ALS has provided some insight into changes in microglia activity during disease progression. The purpose of this study was to gain further knowledge by characterizing the immunological changes during disease progression in the spinal cord and peripheral nerve using the more recently developed hmSOD1 rat transgenic model of ALS. Using immunohistochemistry, the extent and intensity of tissue CD11b expression in spinal cord, lumbar nerve roots, and sciatic nerve were evaluated in hmSOD1 rats that were …

The Site Specific Demethylation In The 5'-Regulatory Area Of Nmda Receptor 2b Subunit Gene Associated With Cie-Induced Up-Regulation Of Transcription., Mei Qiang, Ashley Denny, Jiguo Chen, Maharaj K. Ticku, Bo Yan, George Henderson

CAS Publications

BACKGROUND: The NMDA receptor represents a particularly important site of ethanol action in the CNS. We recently reported that NMDA receptor 2B (NR2B) gene expression was persistently up-regulated following chronic intermittent ethanol (CIE) treatment. Increasing evidence that epigenetic mechanisms are involved in dynamic and long-lasting regulation of gene expression in multiple neuroadaptive processes prompted us to investigate the role of DNA methylation in mediating CIE-induced up-regulation of NR2B gene transcription. To dissect the changes of DNA methylation in the NR2B gene, we have screened a large number of CpG sites within its 5'-regulatory area following CIE treatment. METHODS: Primary cortical …

Genomic Profiling Of Messenger Rnas And Micrornas Reveals Potential Mechanisms Of Tweak-Induced Skeletal Muscle Wasting In Mice, Siva K. Panguluri, Shephali Bhatnagar, Akhilesh Kumar, John J. Mccarthy, Apurva K. Srivastava, Nigel G. Cooper, Robert F. Lundy, Ashok Kumar

Physiology Faculty Publications

BACKGROUND: Skeletal muscle wasting is a devastating complication of several physiological and pathophysiological conditions. Inflammatory cytokines play an important role in the loss of skeletal muscle mass in various chronic diseases. We have recently reported that proinflammatory cytokine TWEAK is a major muscle-wasting cytokine. Emerging evidence suggests that gene expression is regulated not only at transcriptional level but also at post-transcriptional level through the expression of specific non-coding microRNAs (miRs) which can affect the stability and/or translation of target mRNA. However, the role of miRs in skeletal muscle wasting is unknown.

METHODOLOGY/PRINCIPAL FINDINGS: To understand the mechanism of action of …

Il-28 Supplants Requirement For Treg Cells In Protein Σ1-Mediated Protection Against Murine Experimental Autoimmune Encephalomyelitis (Eae), Agnieszka Rynda, Massimo Maddaloni, Javier Ochoa-Repáraz, Gayle Callis, David W. Pascual

Dartmouth Scholarship

Conventional methods to induce tolerance in humans have met with limited success. Hence, efforts to redirect tolerogen uptake using reovirus adhesin, protein sigma 1 (pσ1), may circumvent these shortcomings based upon the recent finding that when reovirus pσ1 is engineered to deliver chicken ovalbumin (OVA) mucosally, tolerance is obtained, even with a single dose. To test whether single-dose tolerance can be induced to treat EAE, proteolipid protein (PLP_130–151) was genetically fused to OVA to pσ1 (PLP:OVA-pσ1) and shown to significantly ameliorate EAE, suppressing proinflammatory cytokines by IL-10⁺ forkhead box P3 (FoxP3)⁺ CD25⁺CD4⁺ T …

Spatiotemporal Structure Of Molecular Evolution Of H5n1 Highly Pathogenic Avian Influenza Viruses In Vietnam., Margaret A. Carrel, Michael Emch, R. Todd Jobe, Aaron Moody, Xiu-Feng Wan

CVM Publications

BACKGROUND: Vietnam is one of the countries most affected by outbreaks of H5N1 highly pathogenic avian influenza viruses. First identified in Vietnam in poultry in 2001 and in humans in 2004, the virus has since caused 111 cases and 56 deaths in humans. In 2003/2004 H5N1 outbreaks, nearly the entire poultry population of Vietnam was culled. Our earlier study (Wan et al., 2008, PLoS ONE, 3(10): e3462) demonstrated that there have been at least six independent H5N1 introductions into Vietnam and there were nine newly emerged reassortants from 2001 to 2007 in Vietnam. H5N1 viruses in Vietnam cluster distinctly around …

Proliferation Of Aneuploid Human Cells Is Limited By A P53-Dependent Mechanism, Sarah L. Thompson, Duane A. Compton

Dartmouth Scholarship

Most solid tumors are aneuploid, and it has been proposed that aneuploidy is the consequence of an elevated rate of chromosome missegregation in a process called chromosomal instability (CIN). However, the relationship of aneuploidy and CIN is unclear because the proliferation of cultured diploid cells is compromised by chromosome missegregation. The mechanism for this intolerance of nondiploid genomes is unknown. In this study, we show that in otherwise diploid human cells, chromosome missegregation causes a cell cycle delay with nuclear accumulation of the tumor suppressor p53 and the cyclin kinase inhibitor p21. Deletion of the p53 gene permits the accumulation …

Myosin Light Chain Kinase Mediates Transcellular Intravasation Of Breast Cancer Cells Through The Underlying Endothelial Cells: A Three-Dimensional Fret Study, S. Khuon, L. Liang, R. W. Dettman, P. H. S. Sporn, R. B. Wysolmerski, T.-L. Chew

Faculty & Staff Scholarship

No abstract provided.

The Novel Endosomal Membrane Protein Ema Interacts With The Class C Vps-Hops Complex To Promote Endosomal Maturation, Sungsu Kim, Yogesh P. Wairkar, Richard W. Daniels, Aaron Diantonio

Open Access Publications

Endosomal maturation is critical for accurate and efficient cargo transport through endosomal compartments. Here we identify a mutation of the novel Drosophila gene, ema (endosomal maturation defective) in a screen for abnormal synaptic overgrowth and defective protein trafficking. Ema is an endosomal membrane protein required for trafficking of fluid-phase and receptor-mediated endocytic cargos. In the ema mutant, enlarged endosomal compartments accumulate as endosomal maturation fails, with early and late endosomes unable to progress into mature degradative late endosomes and lysosomes. Defective endosomal down-regulation of BMP signaling is responsible for the abnormal synaptic overgrowth. Ema binds to and genetically interacts with …

Developing Emotional Security Among Children Who Have Been Adopted, Kate Trujillo

Electronic Theses and Dissertations

This study investigated the development of emotional security among 6-10 year old children who have been adopted by exposing them to an experimental condition during which they could engage with either a live dog or a robotic dog. The live dog was a certified therapy dog; the robotic dog was a FurReal® toy marketed by Hasbro as "Biscuit." Utilizing a mixed-method embedded experimental design, the experimental condition was intentionally structured to promote engagement between the participant and the dog or robot. 43 children who had been adopted from the child welfare system were randomly assigned to one of two groups. …

Nip/Duoxa Is Essential For Drosophila Embryonic Development And Regulates Oxidative Stress Response., Xiaojun Xie, Jack Hu, Xiping Liu, Hanjuan Qin, Anthony Percival-Smith, Yong Rao, Shawn S C Li

Biochemistry Publications

NIP/DuoxA, originally cloned as a protein capable of binding to the cell fate determinant Numb in Drosophila, was recently identified as a modulator of reactive oxygen species (ROS) production in mammalian systems. Despite biochemical and cellular studies that link NIP/DuoxA to the generation of ROS through the dual oxidase (Duox) enzyme, the in vivo function of NIP/DuoxA has not been characterized to date. Here we report a genetic and functional characterization of nip in Drosophila melanogaster. We show that nip is essential for Drosophila development as nip null mutants die at the 1(st) larval instar. Expression of UAS-nip, but not …

Vertical Dispersal Of Aedes (Stegomyia) Spp. In High-Rise Apartments In Putrajaya, Malaysia, Othman Wan-Norafikah, Wasi Ahmad Nazni, S. Noramiza, S. Shafa'ar-Ko'ohar, A. Azirol-Hisham, R. Nor-Hafizah, M.G. Sumarni, H. Mohd-Hasrul, Mohd Sofian-Azirun, H.L. Lee

Research Publications (2006 to 2010)

A preliminary study on the vertical dispersal of Aedes populations in high-riseapartments was carried out in Presint 9, Putrajaya, Malaysia. Ovitraps were placed indoorswithin four blocks of high-rise apartments from the ground floors (0.0 – 3.0 m) until upto the tenth floors (28.1 – 30.0 m). Aedes aegypti was the dominant species found in theovitraps (87.85%), while Aedes albopictus was found in lower numbers. From total numberof larvae collected (650), 40.92% of these larvae were obtained from the fourth block;Block D. The peak density of Aedes sp. was observed at level 6 (16.1 – 18.0 m), whileAe. aegypti was found …

Oncogenic Src Requires A Wild-Type Counterpart To Regulate Invadopodia Maturation, L. C. Kelley, A. G. Ammer, K. E. Hayes, K. H. Martin, K. Machida, L. Jia, B. J. Mayer, S. A. Weed

Faculty & Staff Scholarship

No abstract provided.

Differential Impact Of Tumor Suppressor Pathways On Dna Damage Response And Therapy-Induced Transformation In A Mouse Primary Cell Model., A Kathleen Mcclendon, Jeffry L Dean, Adam Ertel, Erik S Knudsen

Department of Cancer Biology Faculty Papers

The RB and p53 tumor suppressors are mediators of DNA damage response, and compound inactivation of RB and p53 is a common occurrence in human cancers. Surprisingly, their cooperation in DNA damage signaling in relation to tumorigenesis and therapeutic response remains enigmatic. In the context of individuals with heritable retinoblastoma, there is a predilection for secondary tumor development, which has been associated with the use of radiation-therapy to treat the primary tumor. Furthermore, while germline mutations of the p53 gene are critical drivers for cancer predisposition syndromes, it is postulated that extrinsic stresses play a major role in promoting varying …

Susceptibility Of Field-Collected Aedes Aegypti (L.) (Diptera: Culicidae) To Bacillus Thuringiensis Israelensis And Temephos, S.R. Loke, W.A. Andy-Tan, S. Benjamin, H.L. Lee, Mohd Sofian-Azirun

Research Publications (2006 to 2010)

The susceptibility status of field-collected Aedes aegypti (L.) from a dengue endemic area to Bacillus thuringiensis israelensis (Bti) and temephos was determined. Since August 2007, biweekly ovitrap surveillance (OS) was conducted for 12 mo in 2 sites, A & B, in Shah Alam, Selangor. Site A was treated with a Bti formulation, VectoBac® WG at 500 g/ha, from December 2007 - June 2008 while Site B was subjected to routine dengue vector control activities conducted by the local municipality. Aedes aegypti larvae collected from OS in both sites were bred until F3 and evaluated for their susceptibility. The larvae were …

Electroporation-Mediated Delivery Of A Naked Dna Plasmid Expressing Vegf To The Porcine Heart Enhances Protein Expression, W. G. Marshall Jr., B. A. Boone, J. D. Burgos, S. I. Gografe, M. K. Baldwin, M. L. Danielson, M. J. Larson, D. R. Caretto, Y. Cruz, B. Ferraro, L. C. Heller, K. E. Ugen, M. J. Jaroszeski, R. Heller

Bioelectrics Publications

Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, VEGF), which is a molecule previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without coadministered EP to determine the potential effect of electrically mediated delivery. The results showed that plasmid delivery through EP significantly …

Quantifying Male-Biased Dispersal Among Social Groups In The Collared Peccary (Pecari Tajacu) Using Analyses Based On Mtdna Variation., J D Cooper, R Vitalis, P M Waser, D Gopurenko, E C Hellgren, T M Gabor, J A Dewoody

Publications

Recent advances in the statistical analysis of microsatellite data permit calculation of sex-specific dispersal rates through sex- and age-specific comparisons of genetic variation. This approach, developed for the analysis of data derived from co-dominant autosomal markers, should be applicable to a sex-specific marker such as mitochondrial DNA. To test this premise, we amplified a 449 bp control region DNA sequence from the mitochondrial genome of the collared peccary (Pecari tajacu), and estimated intra-class correlations among herds sampled from three Texas populations. Analyses on data partitioned by breeding group showed a clear signal of male-biased dispersal; sex-specific fixation indices associated with …

Dopamine D1 Receptor-Mediated Nmda Receptor Insertion Depends On Fyn But Not Src Kinase Pathway In Prefrontal Cortical Neurons, Jian-Li Hu, Gang Liu, Yan-Chun Li, Wen-Jun Gao, Yueqiao Huang

PCOM Scholarly Works

Background. Interactions between dopamine and glutamate in the prefrontal cortex are essential for cognitive functions such as working memory. Modulation of N-methyl-D-aspartic acid (NMDA) receptor functions by dopamine D1 receptor is believed to play a critical role in these functions. The aim of the work reported here is to explore the signaling pathway underlying D1 receptor-mediated trafficking of NMDA receptors in cultured rat prefrontal cortical neurons. Results. Activation of D1 receptor by selective agonist SKF-81297 significantly increased the expression of NR2B subunits. This effect was completely blocked by small interfering RNA knockdown of Fyn, but not Src. Under control conditions, …

Cellular Functions Of Fak Kinases: Insight Into Molecular Mechanisms And Novel Functions, M. D. Schaller

Faculty & Staff Scholarship

No abstract provided.

The Relationship Between Mosquito Abundance And Rice Field Density In The Republic Of Korea, Erin E. Richards, Penny Masuoka, David Brett-Major, Matthew Smith, Terry A. Klein, Heung Chul Kim, Assaf Anyamba, John Grieco

Journal Articles: Epidemiology

BACKGROUND: Japanese encephalitis virus (JEV), the causative agent of Japanese encephalitis (JE), is endemic to the Republic of Korea (ROK) where unvaccinated United States (U.S.) military Service members, civilians and family members are stationed. The primary vector of the JEV in the ROK is Culex tritaeniorhynchus. The ecological relationship between Culex spp. and rice fields has been studied extensively; rice fields have been shown to increase the prevalence of Cx. tritaeniorhynchus. This research was conducted to determine if the quantification of rice field land cover surrounding U.S. military installations in the ROK should be used as a parameter in a …

Impact Of Central And Peripheral Trpv1 And Ros Levels On Proinflammatory Mediators And Nociceptive Behavior, Karin N. Westlund, Mikhail Y. Kochukov, Ying Lu, Terry A. Mcnearney

Physiology Faculty Publications

Background: Transient receptor potential vanilloid 1 (TRPV1) channels are important membrane sensors on peripheral nerve endings and on supportive non-neuronal synoviocytes in the knee joint. TRPV 1 ion channels respond with activation of calcium and sodium fluxes to pH, thermal, chemical, osmotic, mechanical and other stimuli abundant in inflamed joints. In the present study, the kaolin/carrageenan (k/c) induced knee joint arthritis model in rats, as well as primary and clonal human synoviocyte cultures were used to understand the reciprocal interactions between reactive nitroxidative species (ROS) and functional TRPV1 channels. ROS generation was monitored with ROS sensitive dyes using live cell …

Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets With Alopecia Resulting From A Novel Missense Mutation In The Dna-Binding Domain Of The Vitamin D Receptor., Peter J. Malloy, Jining Wang, Tarak Srivastava, David Feldman

Manuscripts, Articles, Book Chapters and Other Papers

The rare genetic recessive disease, hereditary vitamin D resistant rickets (HVDRR), is caused by mutations in the vitamin D receptor (VDR) that result in resistance to the active hormone 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3) or calcitriol). In this study, we examined the VDR from a young boy with clinical features of HVDRR including severe rickets, hypocalcemia, hypophosphatemia and partial alopecia. The pattern of alopecia was very unusual with areas of total baldness, adjacent to normal hair and regions of scant hair. The child failed to improve on oral calcium and vitamin D therapy but his abnormal chemistries and his bone X-rays normalized …

Interaction Of The Mu-Opioid Receptor With Gpr177 (Wntless) Inhibits Wnt Secretion: Potential Implications For Opioid Dependence., Jay Jin, Saranya Kittanakom, Victoria Wong, Beverly A S Reyes, Elisabeth J Van Bockstaele, Igor Stagljar, Wade Berrettini, Robert Levenson

Department of Neurosurgery Faculty Papers

BACKGROUND: Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of opioid dependence. RESULTS: GPR177, the mammalian ortholog of Drosophila …

Recent Advances On Skin-Resident Stem/Progenitor Cell Functions In Skin Regeneration, Aging And Cancers And Novel Anti-Aging And Cancer Therapies., Murielle Mimeault, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Recent advances in skin-resident adult stem/progenitor cell research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals. The establishment of the functional properties of distinct adult stem/progenitor cells found in skin epidermis and hair follicles and extrinsic signals from their niches, which are deregulated during their aging and malignant transformation, has significantly improved our understanding on the etiopathogenesis of diverse human skin disorders and cancers. Particularly, enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging …

N-P Co-Limitation Of Primary Production And Response Of Arthropods To N And P In Early Primary Succession On Mount St. Helens Volcano, John G. Bishop, Niamh B. O'Hara, Jonathan H. Titus, Jennifer L. Apple, Richard A. Gill, Louise Wynn

Biology

Background: The effect of low nutrient availability on plant-consumer interactions during early succession is poorly understood. The low productivity and complexity of primary successional communities are expected to limit diversity and abundance of arthropods, but few studies have examined arthropod responses to enhanced nutrient supply in this context. We investigated the effects of nitrogen (N) and phosphorus (P) addition on plant productivity and arthropod abundance on 24-yr-old soils at Mount St. Helens volcano. Methodology/Principal Findings:We measured the relative abundance of eight arthropod orders and five families in plots that received N, P, or no nutrients for 3-5 years. We also …

Mine And Thine: The Territorial Foundations Of Human Property, Peter Descioli, Bart J. Wilson

ESI Working Papers

Research shows that many animal species have morphological and cognitive adaptations for fighting with others to gain resources, but it remains unclear how humans make fighting decisions. Non-human animals often adaptively calibrate fighting behavior to ecological variables such as resource quantity and whether the resource is distributed uniformly or clustered in patches. Also, many species use strategies to reduce fighting costs such as resolving disputes based on power asymmetries or conventions. Here we show that humans apply an ownership convention in response to the problem of severe fighting. We designed a virtual environment where ten participants, acting as avatars, could …

More Than Synaptic Plasticity: Role Of Nonsynaptic Plasticity In Learning And Memory, Riccardo Mozzachiodi, John H Byrne

Faculty, Staff and Student Publications

Decades of research on the cellular mechanisms of memory have led to the widely held view that memories are stored as modifications of synaptic strength. These changes involve presynaptic processes, such as direct modulation of the release machinery, or postsynaptic processes, such as modulation of receptor properties. Parallel studies have revealed that memories might also be stored by nonsynaptic processes, such as modulation of voltage-dependent membrane conductances, which are expressed as changes in neuronal excitability. Although in some cases nonsynaptic changes can function as part of the engram itself, they might also serve as mechanisms through which a neural circuit …

Imaging Spontaneous Mmtvneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products., Mathew L Thakur, Devakumar Devadhas, Kaijun Zhang, Richard G Pestell, Chenguang Wang, Peter Mccue, Eric Wickstrom

Department of Radiology Faculty Papers

INTRODUCTION: Despite the great strides made in imaging breast cancer (BC) in humans, the current imaging modalities miss up to 30% of BC, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. Annually in the United States, approximately 5.6 million biopsies find benign lesions. More than 50% of human BCs overexpress cyclin D1, and all BCs exhibit VPAC1 oncogene products. Together, these gene products may provide an excellent biomarker for the early and accurate detection of BC. We have evaluated 4 biologically active peptide analogs that have high affinity for …