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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 …

Cd4+ T Cell Regulation Of Cd25 Expression Controls Development Of Short-Lived Effector Cd8+ T Cells In Primary And Secondary Responses, Joshua J. Obar, Michael J. Molloy, Evan R. Jellison, Thomas A. Stoklasek, Weijun Zhang, Edward J. Usherwood, Leo Lefrançois

Dartmouth Scholarship

Both CD4(+) T cell help and IL-2 have been postulated to "program" activated CD8(+) T cells for memory cell development. However, the linkage between these two signals has not been well elucidated. Here we have studied effector and memory CD8(+) T cell differentiation following infection with three pathogens (Listeria monocytogenes, vesicular stomatitis virus, and vaccinia virus) in the absence of both CD4(+) T cells and IL-2 signaling. We found that expression of CD25 on antigen-specific CD8(+) T cells peaked 3-4 days after initial priming and was dependent on CD4(+) T cell help, likely through a CD28:CD80/86 mediated pathway. CD4(+) T …

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 Public Health Impacts Of Concentrated Animal Feeding Operations On Local Communities, Michael Greger, Gowri Koneswaran

Environment Collection

Large-scale farm animal production facilities, also known as concentrated animal feeding operations (CAFOs), release a significant amount of contaminants into the air and water. Adverse health effects related to exposure to these contaminants among CAFO workers have been welldocumented; however, less is known about their impact on the health of residents in nearby communities. Epidemiological research in this area suggests that neighboring residents are at increased risk of developing neurobehavioral symptoms and respiratory illnesses, including asthma. Additional research is needed to better understand community-scale exposures and health outcomes related to the management practices and emissions of CAFOs.

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. …

Recent Diarrhea Is Associated With Elevated Salivary Igg Responses To Cryptosporidium In Residents Of An Eastern Massachusetts Community, A. I. Egorov, L. M. Montuori Trimble, L. Ascolillo, H. D. Ward, Deborah A. Levy, R. D. Morris, E. N. Naumova, J. K. Griffiths

Journal Articles: Epidemiology

BACKGROUND: Serological data suggest that Cryptosporidium infections are common but underreported. The invasiveness of blood sampling limits the application of serology in epidemiological surveillance. We pilot-tested a non-invasive salivary anti-Cryptosporidium antibody assay in a community survey involving children and adults.

MATERIALS AND METHODS: Families with children were recruited in a Massachusetts community in July; symptoms data were collected at 3 monthly follow-up mail surveys. One saliva sample per person (n = 349) was collected via mail, with the last survey in October. Samples were analyzed for IgG and IgA responses to a recombinant C. hominis gp15 sporozoite protein using a …

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 …

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, …

Prosecutorial Decision Making In The Face Of Changing Norms : An Exploratory Study Of Animal Cruelty Prosecution In New York, Andrea Lynne Kordzek

Legacy Theses & Dissertations (2009 - 2024)

Societal norms regarding the treatment of animals are evolving. This is reflected in part in nationwide changes in criminal justice policy regarding animal welfare. These changes, however, are not likely embraced by all nor do they necessarily result in changes in the practices of decision-makers in the criminal courts. Prosecutorial decision-making in animal cruelty cases may be especially varied due to evolving norms regarding the treatment of animals and conflicting views on the seriousness of the offense, along with the classification of animal cruelty as a relatively low level offense. Research to date has failed to examine how these cases …

The Eagleville Times,Volume 8, Issue 1, Debbie Ryan

Eagleville Times

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 …

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 …

Geographilia In Children's Urban Spaces: Investigating How Children Explore Outdoor Places And Connect With Natural Objects., Jeanine Sandra Garella

Graduate Student Theses, Dissertations, & Professional Papers

ABSTRACT Garella, Jeanine Sandra, M.A., Autumn 2010 Geography Geographilia in Children’s Urban Spaces: Investigating How Children Explore Outdoor Places and Connect With Natural Objects Chairperson: Jeffrey A. Gritzner The benefits children receive from outdoor play time are well documented by scholars across many disciplines. Interacting within an unstructured natural setting can foster physical, social, emotional, and spiritual growth. The lessons learned in such an environment not only help children reach developmental milestones; they also play an important role in the formation of beliefs and attitudes used in decision-making processes later in life. This is a significant point to make when …

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 …

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 …

Type I Ifn Enhances Follicular B Cell Contribution To The T Cell-Independent Antibody Response, Cristina L. Swanson, Timothy J. Wilson, Pamela Strauch, Marco Colonna, Roberta Pelanda, Raul M. Torres

Open Access Publications

Humoral immunity to viruses and encapsulated bacteria is comprised of T cell-independent type 2 (TI-2) antibody responses that are characterized by rapid antibody production by marginal zone and B1 B cells. We demonstrate that toll-like receptor (TLR) ligands influence the TI-2 antibody response not only by enhancing the overall magnitude but also by skewing this response to one that is dominated by IgG isotypes. Importantly, TLR ligands facilitate this response by inducing type I interferon (IFN), which in turn elicits rapid and significant amounts of antigen-specific IgG2c predominantly from FO (follicular) B cells. Furthermore, we show that although the IgG2c …

Sustained Expression Of Tdp-43 And Fus In Motor Neurons In Rodent's Lifetime., Cao Huang, Pedro Yuxing Xia, Hongxia Zhou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS) are two highly conserved ribonucleoproteins. Pathogenic mutations of the TDP-43 or the FUS gene are all linked to amyotrophic lateral sclerosis (ALS) that is characterized by progressive degeneration of motor neurons. To better understand the correlation of ALS disease genes with the selectivity of chronic motor neuron degeneration, we examined the longitudinal expression of the TDP-43 and the FUS genes in C57BL6 mice and in Sprague-Dawley rats. TDP-43 and FUS were robustly and ubiquitously expressed in the postnatal mice and rats, but were markedly decreased in the adult rodents. In adulthood, …

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 …

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 …

Anomalous Constitutive Src Kinase Activity Promotes B Lymphoma Survival And Growth, Jiyuan Ke, R. Lakshman Chelvarajan, Vishal Sindhava, Darrell A. Robertson, Lazaros Lekakis, C. Darrell Jennings, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Previously we have shown that B cell receptor (BCR) expression and B cell receptor signaling pathways are important for the basal growth of B lymphoma cells. In particular we have shown that the activation of Syk, a non-src family protein tyrosine kinase and the mitogen activated protein kinases (MAPK), ERK and JNK that mediate BCR signals are required for the constitutive growth of B lymphoma cells. Since src family protein tyrosine kinases (SFKs) like Lyn are known to be needed for the phosphorylation of BCR co-receptors, Ig-alpha and Ig-beta, we hypothesized that one or more SFKs will be constitutively …

Transcriptional Adaptations Following Exercise In Thoroughbred Horse Skeletal Muscle Highlights Molecular Mechanisms That Lead To Muscle Hypertrophy, Beatrice A. Mcgivney, Suzanne S. Eivers, David E. Machugh, James N. Macleod, Grace M. O'Gorman, Stephen D.E. Park, Lisa M. Katz, Emmeline W. Hill

Veterinary Science Faculty Publications

BACKGROUND: Selection for exercise-adapted phenotypes in the Thoroughbred racehorse has provided a valuable model system to understand molecular responses to exercise in skeletal muscle. Exercise stimulates immediate early molecular responses as well as delayed responses during recovery, resulting in a return to homeostasis and enabling long term adaptation. Global mRNA expression during the immediate-response period has not previously been reported in skeletal muscle following exercise in any species. Also, global gene expression changes in equine skeletal muscle following exercise have not been reported. Therefore, to identify novel genes and key regulatory pathways responsible for exercise adaptation we have used equine-specific …

Chylomicrons Promote Intestinal Absorption And Systemic Dissemination Of Dietary Antigen (Ovalbumin) In Mice, Yuehui Wang, Sarbani Ghoshal, Martin Ward, Willem De Villiers, Jerold Woodward, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: A small fraction of dietary protein survives enzymatic degradation and is absorbed in potentially antigenic form. This can trigger inflammatory responses in patients with celiac disease or food allergies, but typically induces systemic immunological tolerance (oral tolerance). At present it is not clear how dietary antigens are absorbed. Most food staples, including those with common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides (LCT), which stimulate mesenteric lymph flux and postprandial transport of chylomicrons through mesenteric lymph nodes (MLN) and blood. Most dietary antigens, like ovalbumin (OVA), are emulsifiers, predicting affinity for chylomicrons. We hypothesized that chylomicron …

Gbdr Regulates Pseudomonas Aeruginosa Plch And Pchp Transcription In Response To Choline Catabolites, Matthew J. Wargo, Tiffany C. Ho, Maegan J. Gross, Laurie A. Whittaker, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C, PlcH, can degrade phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and extracellular PC in lung surfactant. Numerous studies implicate PlcH in P. aeruginosa virulence. The phosphorylcholine released by PlcH activity on phospholipids is hydrolyzed by a periplasmic phosphorylcholine phosphatase, PchP. Both plcH gene expression and PchP enzyme activity are positively regulated by phosphorylcholine degradation products, including glycine betaine. Here we report that the induction of plcH and pchP transcription by glycine betaine is mediated by GbdR, an AraC family transcription factor. Mutants that lack gbdR are unable to induce plcH and pchP in media …

Germinal Center Reutilization By Newly Activated B Cells., Tanja A Schwickert, Boris Alabyev, Tim Manser, Michel C Nussenzweig

Department of Microbiology and Immunology Faculty Papers

Germinal centers (GCs) are specialized structures in which B lymphocytes undergo clonal expansion, class switch recombination, somatic hypermutation, and affinity maturation. Although these structures were previously thought to contain a limited number of isolated B cell clones, recent in vivo imaging studies revealed that they are in fact dynamic and appear to be open to their environment. We demonstrate that B cells can colonize heterologous GCs. Invasion of primary GCs after subsequent immunization is most efficient when T cell help is shared by the two immune responses; however, it also occurs when the immune responses are entirely unrelated. We conclude …