Life Sciences Commons^™

Identifying Potential Cancer Driver Genes By Genomic Data Integration., Yong Chen, Jingjing Hao, Wei Jiang, Tong He, Xuegong Zhang, Tao Jiang, Rui Jiang

Faculty Scholarship for the College of Science & Mathematics

Cancer is a genomic disease associated with a plethora of gene mutations resulting in a loss of control over vital cellular functions. Among these mutated genes, driver genes are defined as being causally linked to oncogenesis, while passenger genes are thought to be irrelevant for cancer development. With increasing numbers of large-scale genomic datasets available, integrating these genomic data to identify driver genes from aberration regions of cancer genomes becomes an important goal of cancer genome analysis and investigations into mechanisms responsible for cancer development. A computational method, MAXDRIVER, is proposed here to identify potential driver genes on the basis …

Enrichment And Training Improve Cognition In Rats With Cortical Malformations, Kyle R. Jenks, Marcella M. Lucas, Ben A. Duffy, Ashlee A. Robbins, Barjor Gimi, Jeremy M. Barry, Rod C. Scott

Dartmouth Scholarship

Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group …

Contrast Negation Differentiates Visual Pathways Underlying Dynamic And Invariant Facial Processing, Pamela M. Pallett, Ming Meng

Dartmouth Scholarship

Abstract Bruce and Young (1986) proposed a model for face processing that begins with structural encoding, followed by a split into two processing streams: one for the dynamic aspects of the face (e.g., facial expressions of emotion) and the other for the invariant aspects of the face (e.g., gender, identity). Yet how this is accomplished remains unclear. Here, we took a psychophysical approach using contrast negation to test the Bruce and Young model. Previous research suggests that contrast negation impairs processing of invariant features (e.g., gender) but not dynamic features (e.g., expression). In our first experiment, participants discriminated differences in …

Socially Excluded Individuals Fail To Recruit Medial Prefrontal Cortex For Negative Social Scenes, Katherine E. Powers, Dylan D. Wagner, Catherine J. Norris, Todd F. Heatherton

Dartmouth Scholarship

Converging behavioral evidence suggests that people respond to experiences of social exclusion with both defensive and affiliative strategies, allowing them to avoid further distress while also encouraging re-establishment of positive social connections. However, there are unresolved questions regarding the cognitive mechanisms underlying people's responses to social exclusion. Here, we sought to gain insight into these behavioral tendencies by using functional magnetic resonance imaging (fMRI) to examine the impact of social exclusion on neural responses to visual scenes that varied on dimensions of sociality and emotional valence. Compared to socially included participants, socially excluded participants failed to recruit dorsomedial prefrontal cortex …

Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …

The Composite Effect For Inverted Faces Is Reliable At Large Sample Sizes And Requires The Basic Face Configuration, Tirta Susilo, Constantin Rezlescu, Bradley Duchaine

Dartmouth Scholarship

Abstract The absence of the face composite effect (FCE) for inverted faces is often considered evidence that holistic processing operates only on upright faces. However, such absence might be explained by power issues: Most studies that have failed to find the inverted FCE tested 24 participants or less. Here we find that the inverted FCE exists reliably when we tested at least 60 participants. The inverted FCE was ∼ 18% the size of the upright FCE, and it was unaffected by testing order: It did not matter whether participants did the upright condition first (Experiment 1, n = 64) or …

Adam17-Mediated Processing Of Tnf-Α Expressed By Antiviral Effector Cd8+ T Cells Is Required For Severe T-Cell-Mediated Lung Injury, Matthew P. Deberge, Kenneth H. Ely, Guang-Shing Cheng, Richard I. Enelow

Dartmouth Scholarship

Influenza infection in humans evokes a potent CD8+ T-cell response, which is important for clearance of the virus but may also exacerbate pulmonary pathology. We have previously shown in mice that CD8+ T-cell expression of TNF-a is required for severe and lethal lung injury following recognition of an influenza antigen expressed by alveolar epithelial cells. Since TNF-a is first expressed as a transmembrane protein that is then proteolytically processed to release a soluble form, we sought to characterize the role of TNF-a processing in CD8+ T-cell-mediated injury. In this study we observed that inhibition of ADAM17-mediated processing of TNF-a by …

Accommodations For Patients With Disabilities In Primary Care: A Mixed Methods Study Of Practice Administrators, Jennifer Renee Pharr

Environmental & Occupational Health Faculty Publications

Structural barriers that limit access to health care services for people with disabilities have been identified through qualitative studies; however, little is known about how patients with disabilities are accommodated in the clinical setting when a structural barrier is encountered. The purpose of this study was to identify how primary care medical practices in the United States accommodated people with disabilities when a barrier to service is encountered. Primary care practice administrators from the medical management organization were identified through the organization’s website. Sixty-three administrators from across the US participated in this study. Practice administrators reported that patients were examined …

Increased Abundance Of Frost Mrna During Recovery From Cold Stress Is Not Essential For Cold Tolerance In Adult Drosophila Melanogaster., H Udaka, A Percival-Smith, B J Sinclair

Biology Publications

Frost (Fst) is a candidate gene associated with the response to cold in Drosophila melanogaster because Fst mRNA accumulation increases during recovery from low temperature exposure. We investigated the contribution of Fst expression to chill-coma recovery time, acute cold tolerance and rapid cold hardening (RCH) in adult D. melanogaster by knocking down Fst mRNA expression using GAL4/UAS-mediated RNA interference. In this experiment, four UAS-Fst and one tubulin-GAL4 lines were used. We predicted that if Fst is essential for cold tolerance phenotypes, flies with low Fst mRNA levels should be less cold tolerant than flies with normal levels of cold-induced Fst …

A Population-Based Case–Control Study Of Urinary Arsenic Species And Squamous Cell Carcinoma In New Hampshire, Usa, Diane Gilbert-Diamond, Zhigang Li, Ann E. Perry, Steven K. Spencer, A Jay Gandolfi, Margaret R. Karagas

Dartmouth Scholarship

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States.

Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population.

Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and …

The Flexible Fairness: Equality, Earned Entitlement, And Self-Interest, Chunliang Feng, Yi Luo, Ruolei Gu, Lucas S. Broster, Xueyi Shen, Tengxiang Tian, Yue-Jia Luo, Frank Krueger

Behavioral Science Faculty Publications

The current study explored whether earned entitlement modulated the perception of fairness in three experiments. A preliminary resource earning task was added before players decided how to allocate the resource they jointly earned. Participants' decision in allocation, their responses to equal or unequal offers, whether advantageous or disadvantageous, and subjective ratings of fairness were all assessed in the current study. Behavioral results revealed that participants proposed more generous offers and showed enhanced tolerance to disadvantageous unequal offers from others when they performed worse than their presumed "partners," while the reverse was true in the better-performance condition. The subjective ratings also …

Aspirin And Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage In Hyperhomocysteinemic Women., Pratip Chakraborty, Sayani Banerjee, Piyali Saha, Shyam Sundar Nandi, Sunita Sharma, Sourendra K. Goswami, Baidyanath Chakravarty, Syed N. Kabir

Journal Articles: Cellular & Integrative Physiology

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 …

Tricellulin Deficiency Affects Tight Junction Architecture And Cochlear Hair Cells, Gowri Nayak, Sue I. Lee, Rizwan Yousaf, Stephanie E. Edelmann, Claire Trincot, Christina M. Van Itallie, Ghanshyam P. Sinha, Maria Rafeeq, Sherri M. Jones, Inna A. Belyantseva, James M. Anderson, Andrew Forge, Gregory I. Frolenkov, Saima Riazuddin

Physiology Faculty Publications

The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular tight junction protein known as tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated a knockin mouse that carries a mutation orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans. Tricellulin was absent from the tricellular junctions in the inner ear epithelia of the mutant animals, which developed rapidly progressing hearing loss accompanied by loss of mechanosensory cochlear hair cells, while …

Self-Regulatory Depletion Increases Emotional Reactivity In The Amygdala, Dylan D. Wagner, Todd F. Heatherton

Dartmouth Scholarship

The ability to self-regulate can become impaired when people are required to engage in successive acts of effortful self-control, even when self-control occurs in different domains. Here, we used functional neuroimaging to test whether engaging in effortful inhibition in the cognitive domain would lead to putative dysfunction in the emotional domain. Forty-eight participants viewed images of emotional scenes during functional magnetic resonance imaging in two sessions that were separated by a challenging attention control task that required effortful inhibition (depletion group) or not (control group). Compared to the control group, depleted participants showed increased activity in the left amygdala to …

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

Sandra Jones

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 …

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

Sandra Jones

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 …

Key Genes For Modulating Information Flow Play A Temporal Role As Breast Tumor Coexpression Networks Are Dynamically Rewired By Letrozole, Nadia M. Penrod, Jason H. Moore

Dartmouth Scholarship

Genes do not act in isolation but instead as part of complex regulatory networks. To understand how breast tumors adapt to the presence of the drug letrozole, at the molecular level, it is necessary to consider how the expression levels of genes in these networks change relative to one another. Using transcriptomic data generated from sequential tumor biopsy samples, taken at diagnosis, following 10-14 days and following 90 days of letrozole treatment, and a pairwise partial orrelation statistic, we build temporal gene coexpression networks. We characterize the structure of each network and identify genes that hold prominent positions for maintaining …

Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the gastrointestinal phase of listeriosis due to the lack of a small animal model that closely mimics human disease. This paper describes a novel mouse model for oral transmission of L. monocytogenes. Using this model, mice fed L. monocytogenes-contaminated bread have a discrete phase of gastrointestinal infection, followed by varying degrees of systemic spread in susceptible (BALB/c/By/J) or resistant (C57BL/6) mouse strains. During the later stages of the infection, dissemination to the gall bladder and brain is observed. The …

Regulation Of Succinate-Fuelled Mitochondrial Respiration In Liver And Skeletal Muscle Of Hibernating Thirteen-Lined Ground Squirrels., Jason C L Brown, Dillon J Chung, Alex N Cooper, James F Staples

Biology Publications

Hibernating ground squirrels (Ictidomys tridecemlineatus) alternate between two distinct metabolic states throughout winter: torpor, during which metabolic rate (MR) and body temperature (Tb) are considerably suppressed, and interbout euthermia (IBE), during which MR and Tb briefly return to euthermic levels. Previous studies showed suppression of succinate-fuelled respiration during torpor in liver and skeletal muscle mitochondria; however, these studies used only a single, saturating succinate concentration. Therefore, they could not address whether mitochondrial metabolic suppression occurs under physiological substrate concentrations or whether differences in the kinetics of mitochondrial responses to changing substrate concentration might also contribute to mitochondrial metabolic regulation during …

Effects Of Foot Type On Multi-Segment Foot Motion In High- And Low-Arched Female Recreational Athletes, Douglas W. Powell

Doctoral Dissertations

Introduction: Mal-alignment and dysfunction of the foot have been shown to result in an increased rate of injury and unique injury patterns. Aberrant foot function has been shown to contribute to repetitive stress and acute injuries. High-arched athletes have been shown to experience a greater rate of bony injury to the lateral aspect of the lower extremity while low-arched athletes experience greater rates of soft-tissue injury to the medial aspect of the lower extremity. Though foot type has been linked to these injury patterns, the mechanism by which these injury patterns occur remains unknown. Multi-segment foot models have been developed …

Warm Springs, Early Lay Dates, And Double Brooding In A North American Migratory Songbird, The Black-Throated Blue Warbler, Andrea K. Townsend, T. Scott Sillett, Nina K. Lany, Sara A. Kaiser, Nicholas L. Rodenhouse, Michael S. Webster, Richard T. Holmes

Dartmouth Scholarship

Numerous studies have correlated the advancement of lay date in birds with warming climate trends, yet the fitness effects associated with this phenological response have been examined in only a small number of species. Most of these species–primarily insectivorous cavity nesters in Europe–exhibit fitness declines associated with increasing asynchrony with prey. Here, we use 25 years of demographic data, collected from 1986 to 2010, to examine the effects of spring temperature on breeding initiation date, double brooding, and annual fecundity in a Nearctic - Neotropical migratory songbird, the black-throated blue warbler (Setophaga caerulescens). Data were collected from birds breeding at …

Derivation Of Multivariate Syndromic Outcome Metrics For Consistent Testing Across Multiple Models Of Cervical Spinal Cord Injury In Rats, Adam R. Ferguson, Karen-Amanda Irvine, John C. Gensel, Jessica L. Nielson, Amity Lin, Johnathan Ly, Mark R. Segal, Rajiv R. Ratan, Jacqueline C. Bresnahan, Michael S. Beattie

Physiology Faculty Publications

Spinal cord injury (SCI) and other neurological disorders involve complex biological and functional changes. Well-characterized preclinical models provide a powerful tool for understanding mechanisms of disease; however managing information produced by experimental models represents a significant challenge for translating findings across research projects and presents a substantial hurdle for translation of novel therapies to humans. In the present work we demonstrate a novel 'syndromic' information-processing approach for capitalizing on heterogeneous data from diverse preclinical models of SCI to discover translational outcomes for therapeutic testing. We first built a large, detailed repository of preclinical outcome data from 10 years of basic …

Identification Of Cold-Responsive Genes In A New Zealand Alpine Stick Insect Using Rna-Seq., Luke T Dunning, Alice B Dennis, Duckchul Park, Brent J Sinclair, Richard D Newcomb, Thomas R Buckley

Biology Publications

The endemic New Zealand alpine stick insect Micrarchus nov. sp. 2 regularly experiences sub-zero temperatures in the wild. 454-based RNA-Seq was used to generate a de novo transcriptome and differentiate between treatments to investigate the genetic basis of cold tolerance. Non cold-treated individuals were compared to those exposed to 0°C for 1 h followed by a 1 h recovery period at 20°C. We aligned 607,410 Roche 454 reads, generating a transcriptome of 5235 contigs. Differential expression analysis ranked candidate cold responsive genes for qPCR validation by P-value. The top nine up-regulated candidates, together with eight a priori targets identified from …

Population Impacts Of Wolbachia On Aedes Albopictus, James W. Mains, Corey L. Brelsfoard, Philip R. Crain, Yunxin Huang, Stephen L. Dobson

Entomology Faculty Publications

Prior studies have demonstrated that Wolbachia, a commonly occurring bacterium capable of manipulating host reproduction, can affect life history traits in insect hosts, which in turn can have population-level effects. Effects on hosts at the individual level are predicted to impact population dynamics, but the latter has not been examined empirically. Here, we describe a biological model system based on Aedes albopictus (Asian tiger mosquito) that allows for measurement of population dynamics, which has not been accomplished in prior field trials or laboratory designs. The results demonstrate the studied populations to be robust and allow for persistent, closed populations with …

The Effects Of Heading On Neurocognitive Function In Female Collegiate Soccer Players During An Entire Soccer Season, Sarah E. Nonaka, Scott Mclean, Jimmy Smith

International Journal of Exercise Science: Conference Proceedings

Recently, much debate has occurred regarding the effects of repeated heading by soccer players on their neurocognitive function. PURPOSE: To determine the effects of heading on neurocognitive function in female collegiate soccer players during an entire soccer season. METHODS: Twenty-four members of the 2012 Southwestern University Women’s Soccer team completed the ImPACT test during preseason and postseason, and self-reported the number of headers for the week immediately prior to each testing session. Amount of playing time for each player was determined from records obtained from the Southwestern University Athletics Department. The six composite scores and the cognitive efficiency index from …

Implicitly Priming The Social Brain: Failure To Find Neural Effects, Katherine E. Powers, Todd F. Heatherton

Dartmouth Scholarship

Humans have a fundamental need for social relationships. Rejection from social groups is especially detrimental, rendering the ability to detect threats to social relationships and respond in adaptive ways critical. Indeed, previous research has shown that experiencing social rejection alters the processing of subsequent social cues in a variety of socially affiliative and avoidant ways. Because social perception and cognition occurs spontaneously and automatically, detecting threats to social relationships may occur without conscious awareness or control. Here, we investigated the automaticity of social threat detection by examining how implicit primes affect neural responses to social stimuli. However, despite using a …

Wolbachia Association With The Tsetse Fly, Glossina Fuscipes Fuscipes, Reveals High Levels Of Genetic Diversity And Complex Evolutionary Dynamics, Rebecca E. Symula, Uzma Alam, Corey L. Brelsfoard, Yineng Wu, Richard Echodu, Loyce M. Okedi, Serap Aksoy, Adalgisa Caccone

Entomology Faculty Publications

BACKGROUND: Wolbachia pipientis, a diverse group of α-proteobacteria, can alter arthropod host reproduction and confer a reproductive advantage to Wolbachia-infected females (cytoplasmic incompatibility (CI)). This advantage can alter host population genetics because Wolbachia-infected females produce more offspring with their own mitochondrial DNA (mtDNA) haplotypes than uninfected females. Thus, these host haplotypes become common or fixed (selective sweep). Although simulations suggest that for a CI-mediated sweep to occur, there must be a transient phase with repeated initial infections of multiple individual hosts by different Wolbachia strains, this has not been observed empirically. Wolbachia has been found in the tsetse fly, Glossina …

Initial Multicenter Experience With Double Nucleoside Therapy For Human Immunodeficiency Virus Infection During Pregnancy, Neal S. Silverman, D. Heather Watts, Joseph Hitti, D. M. Money, E. Livingston, J. Axelrod, J. M. Ernest, Douglas Robbins, M. M. Divito

Neal Silverman

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV …

Community Outreach And Engagement To Prepare For Household Recruitment Of National Children's Study Participants In A Rural Setting, Nancy L. Fahrenwald, Betty Wey, Ann Martin, Bonny L. Specker

Ethel Austin Martin Program Publications

CONTEXT: The National Children's Study (NCS) is a longitudinal study of environmental influences on children's health. Recruitment of a representative birth cohort that will be followed until 21 years of age requires unique approaches across the nationwide study communities.
PURPOSE: To describe community outreach and engagement in preparation for household recruitment of women of childbearing age at a rural-classified NCS location that includes 4 adjacent Northern Plains counties spanning 2,500 square miles.
METHODS: Outreach and engagement methods focused on rural community characteristics. The team established an advisory council, conducted outreach meetings with agencies and groups, participated in local events, and …

Predicting Barriers To Primary Care For Patients With Disabilities: A Mixed Methods Study Of Practice Administrators, Jennifer Renee Pharr, Michelle Chino

Environmental & Occupational Health Faculty Publications

Background. People with disabilities continue to be identified as a group who experience disparate health/health care. They are less likely to engage in some health care services. Structural barriers are often identified as one of the reasons for the underutilization of some health care services by people with disabilities. However, to date no study has been conducted to understand why structural barriers persist twenty years after the Americans with Disabilities Act (ADA) became law.

Objectives. We examined the relationship between primary care practice administrators’ knowledge of the ADA and the number of accessibility barriers that patients with mobility disabilities might …