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Functional Local Renin-Angiotensin System In Human And Rat Periodontal Tissue, Carlos Ferreira Santos, Ana Carolina Morandini, Thiago José Dionísio, Flávio A. Faria, Marta C. Lima, Caio M. Figueiredo, Bella L. Colombini-Ishikiriama, Carla Renata Sipert, Rubens P. Maciel, Ana P. Akashi, Gabriela P. Souza, Gustavo P. Garlet, Camila O. Rodini, Sandra L. Amaral, Christiane Becari, Maria C. Salgado, Eduardo B. Oliveira, Isaac Matus, Daniela N. Didier, Andrew S. Greene Jan 2015

Functional Local Renin-Angiotensin System In Human And Rat Periodontal Tissue, Carlos Ferreira Santos, Ana Carolina Morandini, Thiago José Dionísio, Flávio A. Faria, Marta C. Lima, Caio M. Figueiredo, Bella L. Colombini-Ishikiriama, Carla Renata Sipert, Rubens P. Maciel, Ana P. Akashi, Gabriela P. Souza, Gustavo P. Garlet, Camila O. Rodini, Sandra L. Amaral, Christiane Becari, Maria C. Salgado, Eduardo B. Oliveira, Isaac Matus, Daniela N. Didier, Andrew S. Greene

All Dugoni School of Dentistry Faculty Articles

The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression …


Enhanced Visual Statistical Learning In Adults With Autism., Matthew E. Roser, Richard N. Aslin, Rebecca Mckenzie, Daniel Zahra, József Fiser Jan 2015

Enhanced Visual Statistical Learning In Adults With Autism., Matthew E. Roser, Richard N. Aslin, Rebecca Mckenzie, Daniel Zahra, József Fiser

School of Psychology

OBJECTIVE: Individuals with autism spectrum disorder (ASD) are often characterized as having social engagement and language deficiencies, but a sparing of visuospatial processing and short-term memory (STM), with some evidence of supranormal levels of performance in these domains. The present study expanded on this evidence by investigating the observational learning of visuospatial concepts from patterns of covariation across multiple exemplars. METHOD: Child and adult participants with ASD, and age-matched control participants, viewed multishape arrays composed from a random combination of pairs of shapes that were each positioned in a fixed spatial arrangement. RESULTS: After this passive exposure phase, a posttest …


A New Cecal Slurry Preparation Protocol With Improved Long-Term Reproducibility For Animal Models Of Sepsis, Marlene E. Starr, Allison M. Steele, Mizuki Saito, Bill J. Hacker, B. Mark Evers, Hiroshi Saito Dec 2014

A New Cecal Slurry Preparation Protocol With Improved Long-Term Reproducibility For Animal Models Of Sepsis, Marlene E. Starr, Allison M. Steele, Mizuki Saito, Bill J. Hacker, B. Mark Evers, Hiroshi Saito

Surgery Faculty Publications

Sepsis, a life-threatening systemic inflammatory response syndrome induced by infection, is widely studied using laboratory animal models. While cecal-ligation and puncture (CLP) is considered the gold standard model for sepsis research, it may not be preferable for experiments comparing animals of different size or under different dietary regimens. By comparing cecum size, shape, and cecal content characteristics in mice under different experimental conditions (aging, diabetes, pancreatitis), we show that cecum variability could be problematic for some CLP experiments. The cecal slurry (CS) injection model, in which the cecal contents of a laboratory animal are injected intraperitoneally to other animals, is …


Cyclooxygenase-2, Prostaglandin E2, And Prostanoid Receptor Ep2 In Fluid Flow Shear Stress-Mediated Injury In The Solitary Kidney., Tarak Srivastava, Uri S. Alon, Patricia A. Cudmore, Belal Tarakji, Alexander Kats, Robert E. Garola, R Scott Duncan, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Lynda F. Bonewald, Ashraf El-Meanawy, Virginia J. Savin, Mukut Sharma Dec 2014

Cyclooxygenase-2, Prostaglandin E2, And Prostanoid Receptor Ep2 In Fluid Flow Shear Stress-Mediated Injury In The Solitary Kidney., Tarak Srivastava, Uri S. Alon, Patricia A. Cudmore, Belal Tarakji, Alexander Kats, Robert E. Garola, R Scott Duncan, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Lynda F. Bonewald, Ashraf El-Meanawy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Hyperfiltration subjects podocytes to increased tensile stress and fluid flow shear stress (FFSS). We showed a 1.5- to 2.0-fold increase in FFSS in uninephrectomized animals and altered podocyte actin cytoskeleton and increased synthesis of prostaglandin E2 (PGE2) following in vitro application of FFSS. We hypothesized that increased FFSS mediates cellular changes through specific receptors of PGE2. Presently, we studied the effect of FFSS on cultured podocytes and decapsulated isolated glomeruli in vitro, and on solitary kidney in uninephrectomized sv129 mice. In cultured podocytes, FFSS resulted in increased gene and protein expression of cyclooxygenase (COX)-2 but not COX-1, prostanoid receptor EP2 …


Launching A Virtual Decision Lab: Development And Field-Testing Of A Web-Based Patient Decision Support Research Platform, Aubri S. Hoffman, Hilary A. Llewellyn-Thomas, Anna N. A. Tosteson, Annette M. Oconnor Dec 2014

Launching A Virtual Decision Lab: Development And Field-Testing Of A Web-Based Patient Decision Support Research Platform, Aubri S. Hoffman, Hilary A. Llewellyn-Thomas, Anna N. A. Tosteson, Annette M. Oconnor

Dartmouth Scholarship

Over 100 trials show that patient decision aids effectively improve patients’ information comprehension and values-based decision making. However, gaps remain in our understanding of several fundamental and applied questions, particularly related to the design of interactive, personalized decision aids. This paper describes an interdisciplinary development process for, and early field testing of, a web-based patient decision support research platform, or virtual decision lab, to address these questions.


Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman Dec 2014

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …


Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang Dec 2014

Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang

Dartmouth Scholarship

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4−/−) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4−/− mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression …


Mastl Kinase, A Promising Therapeutic Target, Promotes Cancer Recurrence., Ling Wang, Vivian Q. Luong, Peter J. Giannini, Aimin Peng Nov 2014

Mastl Kinase, A Promising Therapeutic Target, Promotes Cancer Recurrence., Ling Wang, Vivian Q. Luong, Peter J. Giannini, Aimin Peng

Journal Articles: College of Dentistry

Mastl kinase promotes mitotic progression and cell cycle reentry after DNA damage. We report here that Mastl is frequently upregulated in various types of cancer. This upregulation was correlated with cancer progression in breast and oral cancer, poor patient survival in breast cancer, and tumor recurrence in head and neck squamous cell carcinoma. We further investigated the role of Mastl in tumor resistance using cell lines derived from the initial and recurrent tumors of the same head and neck squamous cell carcinoma patients. Ectopic expression of Mastl in the initial tumor cells strongly promoted cell proliferation in the presence of …


The Omega-3 Fatty Acid Docosahexaenoic Acid Attenuates Organic Dust-Induced Airway Inflammation., Tara M. Nordgren, Taylor D. Friemel, Art J. Heires, Jill A. Poole, Todd A. Wyatt, Debra J. Romberger Nov 2014

The Omega-3 Fatty Acid Docosahexaenoic Acid Attenuates Organic Dust-Induced Airway Inflammation., Tara M. Nordgren, Taylor D. Friemel, Art J. Heires, Jill A. Poole, Todd A. Wyatt, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Workers exposed to organic dusts from concentrated animal feeding operations (CAFOs) are at risk for developing airway inflammatory diseases. Available preventative and therapeutic measures for alleviating dust-induced lung disease are inadequate. Because omega-3 fatty acids can mitigate inflammatory processes, we aimed to determine whether nutritional supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA) could reduce the airway inflammatory consequences of exposures to organic dust. Aqueous extracts of organic dusts from swine CAFOs (ODE) were utilized. In DHA-pretreated human bronchial epithelial cells, lung fibroblasts, monocyte cell cultures, and precision-cut murine lung slices, we found that DHA pretreatment dose-dependently decreased ODE-induced …


Cannabinoid Receptor 2 Agonist Attenuates Pain Related Behavior In Rats With Chronic Alcohol/High Fat Diet Induced Pancreatitis, Liping Zhang, Robert H. Kline Iv, Terry A. Mcnearney, Michael P. Johnson, Karin Westlund High Nov 2014

Cannabinoid Receptor 2 Agonist Attenuates Pain Related Behavior In Rats With Chronic Alcohol/High Fat Diet Induced Pancreatitis, Liping Zhang, Robert H. Kline Iv, Terry A. Mcnearney, Michael P. Johnson, Karin Westlund High

Physiology Faculty Publications

BACKGROUND: Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in …


Novel Mutations And Mutation Combinations Of Ryanodine Receptor In A Chlorantraniliprole Resistant Population Of Plutella Xylostella (L.), Lei Guo, Pei Liang, Xuguo Zhou, Xiwu Gao Nov 2014

Novel Mutations And Mutation Combinations Of Ryanodine Receptor In A Chlorantraniliprole Resistant Population Of Plutella Xylostella (L.), Lei Guo, Pei Liang, Xuguo Zhou, Xiwu Gao

Entomology Faculty Publications

A previous study documented a glycine to glutamic acid mutation (G4946E) in ryanodine receptor (RyR) was highly correlated to diamide insecticide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae). In this study, a field population collected in Yunnan province, China, exhibited a 2128-fold resistance to chlorantraniliprole. Sequence comparison between resistant and susceptible P. xylostella revealed three novel mutations including a glutamic acid to valine substitution (E1338D), a glutamine to leucine substitution (Q4594L) and an isoleucine to methionine substitution (I4790M) in highly conserved regions of RyR. Frequency analysis of all four mutations in this field population showed that the three …


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 Oct 2014

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 …


Successful Mdr-Tb Treatment Regimens Including Amikacin Are Associated With High Rates Of Hearing Loss, Chawangwa Modongo, Rafal S. Sobota, Boikobo Kesenogile, Ronald Ncube Oct 2014

Successful Mdr-Tb Treatment Regimens Including Amikacin Are Associated With High Rates Of Hearing Loss, Chawangwa Modongo, Rafal S. Sobota, Boikobo Kesenogile, Ronald Ncube

Dartmouth Scholarship

Aminoglycosides are a critical component of multidrug-resistant tuberculosis (MDR-TB) treatment but data on their efficacy and adverse effects in Botswana is scarce. We determined the effect of amikacin on treatment outcomes and development of hearing loss in MDR-TB patients. Patients started on MDR-TB treatment between 2006 and 2012 were included. Multivariate analysis was used to determine the effect of amikacin on treatment outcomes and development of hearing loss.


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 Oct 2014

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 Oct 2014

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 …


Influence Of Sex On Chronic Obstructive Pulmonary Disease Risk And Treatment Outcomes, Shambhu Aryal, Enrique Diaz-Guzman, David M. Mannino Oct 2014

Influence Of Sex On Chronic Obstructive Pulmonary Disease Risk And Treatment Outcomes, Shambhu Aryal, Enrique Diaz-Guzman, David M. Mannino

Preventive Medicine and Environmental Health Faculty Publications

Chronic obstructive pulmonary disease (COPD), one of the most common chronic diseases and a leading cause of death, has historically been considered a disease of men. However, there has been a rapid increase in the prevalence, morbidity, and mortality of COPD in women over the last two decades. This has largely been attributed to historical increases in tobacco consumption among women. But the influence of sex on COPD is complex and involves several other factors, including differential susceptibility to the effects of tobacco, anatomic, hormonal, and behavioral differences, and differential response to therapy. Interestingly, nonsmokers with COPD are more likely …


Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster, Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen Oct 2014

Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster, Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen

Faculty, Staff and Students Publications

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of …


Natural Selection On Thermal Performance In A Novel Thermal Environment, Michael L. Logan, Robert M. Cox, Ryan Calsbeek Sep 2014

Natural Selection On Thermal Performance In A Novel Thermal Environment, Michael L. Logan, Robert M. Cox, Ryan Calsbeek

Dartmouth Scholarship

Tropical ectotherms are thought to be especially vulnerable to climate change because they are adapted to relatively stable temperature regimes, such that even small increases in environmental temperature may lead to large decreases in physiological performance. One way in which tropical organisms may mitigate the detrimental effects of warming is through evolutionary change in thermal physiology. The speed and magnitude of this response depend, in part, on the strength of climate-driven selection. However, many ectotherms use behavioral adjustments to maintain preferred body temperatures in the face of environmental variation. These behaviors may shelter individuals from natural selection, preventing evolutionary adaptation …


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 Sep 2014

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 …


The Distribution Pattern Of Halicephalobus Gingivalis In A Horse Is Suggestive Of A Haematogenous Spread Of The Nematode, Christina Henneke, Anna Jespersen, Stine Jacobsen, Martin K. Nielsen, Fintan Mcevoy, Henrik E. Jensen Sep 2014

The Distribution Pattern Of Halicephalobus Gingivalis In A Horse Is Suggestive Of A Haematogenous Spread Of The Nematode, Christina Henneke, Anna Jespersen, Stine Jacobsen, Martin K. Nielsen, Fintan Mcevoy, Henrik E. Jensen

Veterinary Science Faculty Publications

The majority of Halicephalobus gingivalis-infections in horses have been fatal and are usually not diagnosed before necropsy. Therefore, knowledge about the nematode and the pathogenesis of infection in horses is limited. This has resulted in an on-going discussion about the port of entry and subsequent dissemination of H. gingivalis within the host. The present case of H. gingivalis-infection in a horse was diagnosed ante mortem. Post mortem findings, the distribution pattern of H. gingivalis nematodes in the brain, a high prevalence of inflammation in close relation to blood vessels, and the presence of the nematode in multiple organs …


A Dietary-Wide Association Study (Dwas) Of Environmental Metal Exposure In Us Children And Adults, Matthew A. Davis, Diane Gilbert-Diamond, Margaret R. Karagas, Zhigang Li, Jason H. Moore, Scott M. Williams, H. Robert Frost Sep 2014

A Dietary-Wide Association Study (Dwas) Of Environmental Metal Exposure In Us Children And Adults, Matthew A. Davis, Diane Gilbert-Diamond, Margaret R. Karagas, Zhigang Li, Jason H. Moore, Scott M. Williams, H. Robert Frost

Dartmouth Scholarship

Background: A growing body of evidence suggests that exposure to toxic metals occurs through diet but few studies have comprehensively examined dietary sources of exposure in US populations.

Purpose: Our goal was to perform a novel dietary-wide association study (DWAS) to identify specific dietary sources of lead, cadmium, mercury, and arsenic exposure in US children and adults.

Methods: We combined data from the National Health and Nutrition Examination Survey with data from the US Department of Agriculture’s Food Intakes Converted to Retail Commodities Database to examine associations between 49 different foods and environmental metal exposure. Using blood and urinary biomarkers …


Enhancing Immunomodulation On Innate Immunity By Shape Transition Among Rna Triangle, Square And Pentagon Nanovehicles, Emil F. Khisamutdinov, Hui Li, Daniel L. Jasinski, Jiao Chen, Jian Fu, Peixuan Guo Sep 2014

Enhancing Immunomodulation On Innate Immunity By Shape Transition Among Rna Triangle, Square And Pentagon Nanovehicles, Emil F. Khisamutdinov, Hui Li, Daniel L. Jasinski, Jiao Chen, Jian Fu, Peixuan Guo

Center for Research on Environmental Disease Faculty Publications

Modulation of immune response is important in cancer immunotherapy, vaccine adjuvant development and inflammatory or immune disease therapy. Here we report the development of new immunomodulators via control of shape transition among RNA triangle, square and pentagon. Changing one RNA strand in polygons automatically induced the stretching of the interior angle from 60° to 90° or 108°, resulting in self-assembly of elegant RNA triangles, squares and pentagons. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-α and IL-6 induction was greatly enhanced in vitro and in animals up to 100-fold, while RNA polygon controls induced unnoticeable effect. The …


Olanzapine-Induced Methylation Alters Cadherin Gene Families And Associated Pathways Implicated In Psychosis, Melkaye G. Melka, Christina A Castellani, Nagalingam Rajakumar, Richard O'Reilly, Shiva M Singh Sep 2014

Olanzapine-Induced Methylation Alters Cadherin Gene Families And Associated Pathways Implicated In Psychosis, Melkaye G. Melka, Christina A Castellani, Nagalingam Rajakumar, Richard O'Reilly, Shiva M Singh

Biology Publications

BACKGROUND: The complex aetiology of most mental disorders involves gene-environment interactions that may operate using epigenetic mechanisms particularly DNA methylation. It may explain many of the features seen in mental disorders including transmission, expression and antipsychotic treatment responses. This report deals with the assessment of DNA methylation in response to an antipsychotic drug (olanzapine) on brain (cerebellum and hippocampus), and liver as a non-neural reference in a rat model. The study focuses on the Cadherin/protocadherins encoded by a multi-gene family that serve as adhesion molecules and are involved in cell-cell communication in the mammalian brain. A number of these molecules …


Sharp Emergence Of Feature-Selective Sustained Activity Along The Dorsal Visual Pathway., Diego Mendoza-Halliday, Santiago Torres, Julio C Martinez-Trujillo Sep 2014

Sharp Emergence Of Feature-Selective Sustained Activity Along The Dorsal Visual Pathway., Diego Mendoza-Halliday, Santiago Torres, Julio C Martinez-Trujillo

Brain and Mind Institute Researchers' Publications

Sustained activity encoding visual working memory representations has been observed in several cortical areas of primates. Where along the visual pathways this activity emerges remains unknown. Here we show in macaques that sustained spiking activity encoding memorized visual motion directions is absent in direction-selective neurons in early visual area middle temporal (MT). However, it is robustly present immediately downstream, in multimodal association area medial superior temporal (MST), as well as and in the lateral prefrontal cortex (LPFC). This sharp emergence of sustained activity along the dorsal visual pathway suggests a functional boundary between early visual areas, which encode sensory inputs, …


Cytokine Gene Expression Profiles During Initiation, Progression And Resolution Of Periodontitis, Jeffrey L. Ebersole, Sreenatha S. Kirakodu, Michael John Novak, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Armando Burgos, Octavio A. Gonzalez Sep 2014

Cytokine Gene Expression Profiles During Initiation, Progression And Resolution Of Periodontitis, Jeffrey L. Ebersole, Sreenatha S. Kirakodu, Michael John Novak, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Armando Burgos, Octavio A. Gonzalez

Center for Oral Health Research Faculty Publications

AIM: Variations in the expression of cytokines during the progression of periodontitis remain ill-defined. We evaluated the expression of 19 cytokine genes related to T-cell phenotype/function during initiation, progression and resolution of periodontitis, and related these to the expression of soft and bone tissue destruction genes (TDGs).

MATERIALS AND METHODS: A ligature-induced periodontitis model was used in rhesus monkeys (M. mulatta) (n = 18). Gingival tissues were taken at baseline pre-ligation, 2 weeks and 1 month (Initiation) and 3 months (progression) post ligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated and the Rhesus …


Loss Of 4e-Bp1 Function Induces Emt And Promotes Cancer Cell Migration And Invasion Via Cap-Dependent Translational Activation Of Snail, Weijia Cai, Qing Ye, Qing-Bai She Aug 2014

Loss Of 4e-Bp1 Function Induces Emt And Promotes Cancer Cell Migration And Invasion Via Cap-Dependent Translational Activation Of Snail, Weijia Cai, Qing Ye, Qing-Bai She

Markey Cancer Center Faculty Publications

The cap-dependent translation is frequently deregulated in a variety of cancers associated with tumor progression. However, the molecular basis of the translation activation for metastatic progression of cancer remains largely elusive. Here, we demonstrate that activation of cap-dependent translation by silencing the translational repressor 4E-BP1 causes cancer epithelial cells to undergo epithelial-mesenchymal transition (EMT), which is associated with selective upregulation of the EMT inducer Snail followed by repression of E-cadherin expression and promotion of cell migratory and invasive capabilities as well as metastasis. Conversely, inhibition of cap-dependent translation by a dominant active mutant 4E-BP1 effectively downregulates Snail expression and suppresses …


Bursts And Heavy Tails In Temporal And Sequential Dynamics Of Foraging Decisions, Kanghoon Jung, Hyeran Jang, Jerald D. D. Kralik, Jaeseung Jeong Aug 2014

Bursts And Heavy Tails In Temporal And Sequential Dynamics Of Foraging Decisions, Kanghoon Jung, Hyeran Jang, Jerald D. D. Kralik, Jaeseung Jeong

Dartmouth Scholarship

A fundamental understanding of behavior requires predicting when and what an individual will choose. However, the actual temporal and sequential dynamics of successive choices made among multiple alternatives remain unclear. In the current study, we tested the hypothesis that there is a general bursting property in both the timing and sequential patterns of foraging decisions. We conducted a foraging experiment in which rats chose among four different foods over a continuous two-week time period. Regarding when choices were made, we found bursts of rapidly occurring actions, separated by time-varying inactive periods, partially based on a circadian rhythm. Regarding what was …


Placental Fkbp5 Genetic And Epigenetic Variation Is Associated With Infant Neurobehavioral Outcomes In The Richs Cohort, Alison G. Paquette, Barry M. Lester, Devin C. Koestler, Corina Lesseur, David A. Armstrong, Carmen J. Marsit Aug 2014

Placental Fkbp5 Genetic And Epigenetic Variation Is Associated With Infant Neurobehavioral Outcomes In The Richs Cohort, Alison G. Paquette, Barry M. Lester, Devin C. Koestler, Corina Lesseur, David A. Armstrong, Carmen J. Marsit

Dartmouth Scholarship

Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function. FK506 binding protein (FKBP5) is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults. We hypothesized that placental FKBP5 methylation and genetic variation contribute to gene expression control, and are associated with infant neurodevelopmental outcomes assessed using the Neonatal Intensive Care Unit (NICU) Network …


Hair Cortisol As A Biomarker Of Stress In Mindfulness Training For Smokers., Simon B Goldberg, Alison R Manley, Stevens S Smith, Jeffrey M Greeson, Evan Russell, Stan Van Uum, Gideon Koren, James M Davis Aug 2014

Hair Cortisol As A Biomarker Of Stress In Mindfulness Training For Smokers., Simon B Goldberg, Alison R Manley, Stevens S Smith, Jeffrey M Greeson, Evan Russell, Stan Van Uum, Gideon Koren, James M Davis

College of Science & Mathematics Departmental Research

OBJECTIVES: Stress is a well-known predictor of smoking relapse, and cortisol is a primary biomarker of stress. The current pilot study examined changes in levels of cortisol in hair within the context of two time-intensity matched behavioral smoking cessation treatments: mindfulness training for smokers and a cognitive-behavioral comparison group.

PARTICIPANTS: Eighteen participants were recruited from a larger randomized controlled trial of smoking cessation.

OUTCOME MEASURES: Hair samples (3 cm) were obtained 1 month after quit attempt, allowing for a retrospective analysis of hair cortisol at preintervention and post-quit attempt time periods. Self-reported negative affect was also assessed before and after …


Implantation Failure In Female Kiss1-/- Mice Is Independent Of Their Hypogonadic State And Can Be Partially Rescued By Leukemia Inhibitory Factor., Michele Calder, Yee-Ming Chan, Renju Raj, Macarena Pampillo, Adrienne Elbert, Michelle Noonan, Carolina Gillio-Meina, Claudia Caligioni, Nathalie G Bérubé, Moshmi Bhattacharya, Andrew J Watson, Stephanie B Seminara, Andy V Babwah Aug 2014

Implantation Failure In Female Kiss1-/- Mice Is Independent Of Their Hypogonadic State And Can Be Partially Rescued By Leukemia Inhibitory Factor., Michele Calder, Yee-Ming Chan, Renju Raj, Macarena Pampillo, Adrienne Elbert, Michelle Noonan, Carolina Gillio-Meina, Claudia Caligioni, Nathalie G Bérubé, Moshmi Bhattacharya, Andrew J Watson, Stephanie B Seminara, Andy V Babwah

Obstetrics & Gynaecology Publications

The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility, a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1(-/-) female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating, and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1(+/-) embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse …