Life Sciences Commons^™

Multifactorial Patterns Of Gene Expression In Colonic Epithelial Cells Predict Disease Phenotypes In Experimental Colitis, Aubrey Leigh Frantz, Maria E. C. Bruno, Eric William Rogier, Halide Tuna, Donald A. Cohen, Subbarao Bondada, Ralph Lakshman Chelvarajan, J. Anthony Brandon, C. Darrell Jennings, Charlotte S. Kaetzel

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background— The pathogenesis of inflammatory bowel disease (IBD) is complex and the need to identify molecular biomarkers is critical. Epithelial cells play a central role in maintaining intestinal homeostasis. We previously identified five “signature” biomarkers in colonic epithelial cells (CEC) that are predictive of disease phenotype in Crohn's disease. Here we investigate the ability of CEC biomarkers to define the mechanism and severity of intestinal inflammation.

Methods— We analyzed the expression of RelA, A20, pIgR, tumor necrosis factor (TNF), and macrophage inflammatory protein (MIP)-2 in CEC of mice with dextran sodium sulfate (DSS) acute colitis or T-cell-mediated chronic colitis. …

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo

Gyongyi Szabo

Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …

An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano

Gyongyi Szabo

The importance of chemokines in alcoholic liver injury has been implicated. The role of the chemokine, monocyte chemoattractant protein-1 (MCP-1), elevated in patients with alcoholic liver disease is not yet understood. Here, we evaluated the pathophysiological significance of MCP-1 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), in alcoholic liver injury. The Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1-deficient knockout (KO) mice for 6 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells (KCs) as …

Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

The pathogenesis of nonalcoholic steatohepatitis (NASH) and inflammasome activation involves sequential hits. The inflammasome, which cleaves pro-interleukin-1beta (pro-IL-1beta) into secreted IL-1beta, is induced by endogenous and exogenous danger signals. Lipopolysaccharide (LPS), a toll-like receptor 4 ligand, plays a role in NASH and also activates the inflammasome. In this study, we hypothesized that the inflammasome is activated in NASH by multiple hits involving endogenous and exogenous danger signals. Using mouse models of methionine choline-deficient (MCD) diet-induced NASH and high-fat diet-induced NASH, we found up-regulation of the inflammasome [including NACHT, LRR, and PYD domains-containing protein 3 (NALP3; cryopyrin), apoptosis-associated speck-like CARD-domain containing …

Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins. In contrast, ceramide increased only in the LDL particles. MS-based analyses of the lipid acyl chain composition revealed a marked elevation in C16:0 fatty acid in SM and ceramide, consistent with the prevalence of palmitic acid in the modified diet. …

Perinatal Administration Of Pcp Alters Adult Behaviour In Female Sprague-Dawley Rats, Teresa Du Bois, Xu-Feng Huang, Chao Deng

Xu-Feng Huang

Perinatal phencyclidine (PCP) treatment leads to neuronal damage and causes long-term behavioural alterations in rodents. This study examined the effects of perinatal PCP treatment on behaviour of adult rats in holeboard, elevated plus maze, social interaction and forced swim tests. PCP-treated rats displayed hyperactivity in the holeboard and forced swim tests. These persistent behavioural changes are relevant to the study of psychiatric disorders such as schizophrenia.

Health Disparities Experienced By People With Disabilities In The Us: A Behavioral Risk Factor Surveillance System Study, Jennifer Renee Pharr, Timothy J. Bungum

Environmental & Occupational Health Faculty Publications

The Americans with Disabilities Act became law in 1990; since then research has shown that people with disabilities continue to experience barriers to health care. The purpose of this study was to compare utilization of preventive services, chronic disease rates, and engagement in health risk behaviors of participants with differing severities of disabilities to those without disabilities. This study was a secondary analysis of 2010 data collected in the Behavioral Risk Factor Surveillance System national survey in the United States. Rao Chi square test and logistic regression were employed. Participants with disabilities had significantly higher adjusted odds ratios for all …

Atovaquone Ameliorate Gastrointestinal Toxoplasmosis Complications In A Pregnancy Model, Helieh S. Oz, Thomas Tobin

Physiology Faculty Publications

Background: Toxoplasma is an important source of foodborne hospitalization with no safe and effective therapy against chronic or congenital Toxopalsmosis. Atovaquone is a drug of choice but not approved for use in congenital Toxoplasmosis. We hypothesized atovaquone to be safe and effective against feto-maternal Toxoplasmosis.

Material/Methods: Programmed pregnant mice were i.p. infected with 50–2400 Tachyzoites from Type II strain (clone PTG). Dams were treated daily with atovaquone or sham and monitored for pain, and complications.

Results: Dams developed pain related abdominal hypersensitivity (allodynia) to mechanical stimuli in a Tachyzoites dose dependent manner. Infected dams were anemic and exhibited ascities and …

Do Australian Adolescent Female Fake Tan (Sunless Tan) Users Practice Better Sun-Protection Behaviors Than Non-Users?, Melinda Williams, Sandra Jones, Peter Caputi, Donald Iverson

Don C. Iverson

Objective: To determine differences in sun-protection behaviours, and incidence of sunburn, between Australian adolescent female fake tan users and non-users. Design: Cross sectional survey. Method: 398 adolescent females aged 12 to 18 years participated in a survey at public venues, schools, and online. The main outcome measures were self-reported fake tan usage in the past 12 months, frequency of sunburns and habitual sun-protection behaviours. Setting: Surveys were completed in New South Wales, Australia. Results: The prevalence of self-reported use of fake tanning products in the past 12 months among Australian adolescent females was 34.5%. Female fake tan users were significantly …

School Day Segmented Physical Activity Patterns Of High And Low Active Children, Stuart J. Fairclough, Aaron Beighle, Heather Erwin, Nicola D. Ridgers

Kinesiology and Health Promotion Faculty Publications

BACKGROUND: Variability exists in children's activity patterns due to the association with environmental, social, demographic, and inter-individual factors. This study described accelerometer assessed physical activity patterns of high and low active children during segmented school week days whilst controlling for potential correlates.

METHODS: Two hundred and twenty-three children (mean age: 10.7 ± 0.3 yrs, 55.6% girls, 18.9% overweight/obese) from 8 north-west England primary schools wore ActiGraph GT1M accelerometers for 7 consecutive days during autumn of 2009. ActiGraph counts were converted to minutes of moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) physical activity. Children were classified as high active (HIGH) or …

Resting-State Connectivity Identifies Distinct Functional Networks In Macaque Cingulate Cortex., R Matthew Hutchison, Thilo Womelsdorf, Joseph S Gati, L Stan Leung, Ravi S Menon, Stefan Everling

Physiology and Pharmacology Publications

Subregions of the cingulate cortex represent prominent intersections in the structural networks of the primate brain. The relevance of the cingulate to the structure and dynamics of large-scale networks ultimately requires a link to functional connectivity. Here, we map fine-grained functional connectivity across the complete extent of the macaque (Macaca fascicularis) cingulate cortex and delineate subdivisions pertaining to distinct identifiable networks. In particular, we identified 4 primary networks representing the functional spectrum of the cingulate: somatomotor, attention-orienting, executive, and limbic. The cingulate nodes of these networks originated from separable subfields along the rostral-to-caudal axis and were characterized by positive and …

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.

Eye Size At Birth In Prosimian Primates: Life History Correlates And Growth Patterns, Joshua R. Cummings, Magdalena N. Muchlinski, E. Christopher Kirk, Susan J. Rehorek, Valerie B. Deleon, Timothy D. Smith

Neuroscience Faculty Publications

BACKGROUND: Primates have large eyes relative to head size, which profoundly influence the ontogenetic emergence of facial form. However, growth of the primate eye is only understood in a narrow taxonomic perspective, with information biased toward anthropoids.

METHODOLOGY/PRINCIPAL FINDINGS: We measured eye and bony orbit size in perinatal prosimian primates (17 strepsirrhine taxa and Tarsius syrichta) to infer the extent of prenatal as compared to postnatal eye growth. In addition, multiple linear regression was used to detect relationships of relative eye and orbit diameter to life history variables. ANOVA was used to determine if eye size differed according to activity …

Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan

Dartmouth Scholarship

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two …

A Dna Vaccine Prime Followed By A Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses And Protection, Kejian Yang, Barbara Whalen, Rebecca S Tirabassi, Liisa Selin, Tatyana Levchenko, Vladimir Torchilin, Edward Kislauskis, Dennis Guberski

Vladimir Torchilin

A variety of DNA vaccine prime and recombinant viral boost immunization strategies have been developed to enhance immune responses in humans, but inherent limitations to these strategies exist. There is still an overwhelming need to develop safe and effective approaches that raise broad humoral and T cell-mediated immune responses systemically and on mucosal surfaces. We have developed a novel mucosal immunization regimen that precludes the use of viral vectors yet induces potent T cell responses. Using hepatitis B surface Ag (HBsAg), we observed that vaccination of BALB/c mice with an i.m. HBsAg-DNA vaccine prime followed by an intranasal boost with …

Long-Stay Patients In State Psychiatric Hospitals At The End Of The 20th Century, William Fisher, Paul Barreira, Jeffrey Geller, Andrew White, Alisa Lincoln, Marylou Sudders

Alisa Lincoln

OBJECTIVES: The purpose of this study was to assess the characteristics of long-stay patients in contemporary state psychiatric hospitals and to identify factors representing possible barriers to alternative placements for these patients. METHODS: All patients in inpatient units of the Massachusetts Department of Mental Health who had been hospitalized for at least three years as of April 1, 1999, were assessed by their treatment teams with a standardized data collection instrument. Domains assessed included medical problems, need for nursing care, psychiatric diagnosis, and history of problematic behaviors. RESULTS: The 330 individuals identified as long-stay patients had an array of medical …

A Dna Vaccine Prime Followed By A Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses And Protection, Kejian Yang, Barbara Whalen, Rebecca S Tirabassi, Liisa Selin, Tatyana Levchenko, Vladimir Torchilin, Edward Kislauskis, Dennis Guberski

Tatyana Levchenko

A variety of DNA vaccine prime and recombinant viral boost immunization strategies have been developed to enhance immune responses in humans, but inherent limitations to these strategies exist. There is still an overwhelming need to develop safe and effective approaches that raise broad humoral and T cell-mediated immune responses systemically and on mucosal surfaces. We have developed a novel mucosal immunization regimen that precludes the use of viral vectors yet induces potent T cell responses. Using hepatitis B surface Ag (HBsAg), we observed that vaccination of BALB/c mice with an i.m. HBsAg-DNA vaccine prime followed by an intranasal boost with …

The Responsiveness Of State Mental Health Authorities To Parents With Mental Illness, Kathleen Biebel, Joanne Nicholson, Valerie Williams, Beth Hinden

Joanne Nicholson

The majority of adults with serious mental illness living in the community are parents, many of whom may be receiving services from State Mental Health Authorities (SMHA). Innovative intervention approaches are available to improve outcomes for these parents and their children. Analyses of SMHA and state-level data, as well as qualitative interviews of administrators, service providers, and consumers, underscore the importance of organizational structure and philosophy, an advocacy presence, and available funding to SMHA efforts on behalf of parents and their families.

Mothers With Mental Illness: I. The Competing Demands Of Parenting And Living With Mental Illness, Joanne Nicholson, Elaine Sweeney, Jeffrey Geller

Joanne Nicholson

OBJECTIVE: The purpose of this study is to understand the parenting experiences of women with mental illness from the perspectives of mothers and case managers employed by the state department of mental health. METHODS: Six focus groups of mothers and five focus groups of case managers met to discuss the problems facing mothers with mental illness and to recommend solutions. Focus-group transcripts were coded and items grouped by themes in qualitative analyses to explore the conflicts mothers face in meeting the dual challenges of parenting and living with mental illness. RESULTS: Mothers and case managers identified sources of conflict in …

Mothers With Mental Illness: Ii. Family Relationships And The Context Of Parenting, Joanne Nicholson, Elaine Sweeney, Jeffrey Geller

Joanne Nicholson

OBJECTIVE: This study explores the experiences of mothers with mental illness regarding their family relationships.

METHODS: Six focus groups of mothers with mental illness and five focus groups of case managers met to discuss problems facing mothers with mental illness and to recommend solutions. Focus groups were audiotaped, and transcripts were coded and analyzed qualitatively to describe ways in which husbands and partners, grandparents, and other family members contribute to the context of parenting for mothers with mental illness.

RESULTS: Mothers with mental illness and case managers described a range of relationships and attitudes of family members and provided examples …

Failure Of Alpha-Galactosylceramide To Prevent Diabetes In Virus-Inducible Models Of Type 1 Diabetes In The Rat, Prerna Chopra, Philip Diiorio, Steven Pino, S. Brian Wilson, Nancy Phillips, John Mordes, Aldo Rossini, Dale Greiner, Leonard Shultz, Rita Bortell

Philip J diIorio Jr

BACKGROUND: Alpha-galactosylceramide (alpha-GalCer) is an invariant natural killer T (iNKT) cell ligand that prevents type 1 diabetes in NOD mice. However, alpha-GalCer can activate or suppress immune responses, raising concern about its potential use in human diabetes.

MATERIALS AND METHODS: To evaluate this therapeutic issue further, BBDR and LEW.1WR1 rats were treated with Kilham rat virus (KRV) plus polyinosinic-polycytidylic acid, with or without alpha-GalCer, and followed for onset of diabetes.

RESULTS: alpha-GalCer did not prevent diabetes in inducible rat models. To investigate this discrepancy, we analyzed iNKT cell function. Splenocytes stimulated with alpha-GalCer produced similar levels of IFNgamma in all …

Patterns And Predictors Of Mammography Utilization Among Breast Cancer Survivors, Chyke Doubeni, Terry Field, Marianne Yood, Sharon Rolnick, Charles Quessenberry, Hassan Fouayzi, Jerry Gurwitz, Feifei Wei

Chyke A. Doubeni

BACKGROUND: Improvements in cancer detection and treatment have resulted in increasing numbers of breast cancer survivors. Information regarding the use of mammography by breast cancer survivors is limited. METHODS: The use of surveillance mammography was examined over a 5-year period in a retrospective cohort of women age>or=55 years who were diagnosed with incident primary breast cancer (1996-1997) while enrolled in 1 of 4 geographically diverse integrated health systems. RESULTS: Of the 797 women included in the study, 80% (n=636) underwent mammograms during the first year after treatment for breast cancer. The percentage of women having mammograms during each yearly …

A Hangover And A One-Night Stand: Alcohol And Risky Sexual Behaviour Among Female Students At An Australian University, Heidi Gilchrist, Kylie Smith, Christopher A. Magee, Sandra Jones

Faculty of Health and Behavioural Sciences - Papers (Archive)

There is a growing body of research in Australia exploring the alcohol consumption behaviours of young people and the attendant health and social risks associated with excessive use of alcohol (Chikritzhs et al. 2003; Mancina-Pena & Tyson 2007). A number of studies from countries such as the United States and New Zealand indicate that university students tend to drink at riskier levels than the broader population (see for example Wechsler et al. 1994; Kypri, Stephenson & Langley 2005; Wechsler & Nelson 2008). Data from Australia are limited, although the few studies that have been conducted suggest that Australian university students …