Medicine and Health Sciences Commons^™

A Genome-To-Genome Analysis Of Associations Between Human Genetic Variation, Hiv-1 Sequence Diversity, And Viral Control, Istvan Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. Mclaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martinez-Picado, Judith Dalmau, Cecilio Lopez-Galindez, Concepcion Casado, Andri Rauch, Huldrych F. Gunthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O'Brien, Jennifer Listgarten, Nico Pfeifer, Christoph Lippert, Nicolo Fusi, Zoltan Kutalik, Todd M. Allen, Viktor Muller, P. Richard Harrigan, David Heckerman, Amalio Telenti, Jacques Fellay

Biology Faculty Articles

HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10⁻¹²). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation …

Deep Sequencing Analyses Expands The Pseudomonas Aeruginosa Ampr Regulon To Include Small Rna-Mediated Regulation Of Iron Acquisition, Heat Shock And Oxidative Stress Response, Deepak Balasubramania, Hansi Kumari, Melita Jaric, Mitch Fernandez, Keith H. Turner, Simon L. Dove, Giri Narasimhan, Stephen Lory, Kalai Mathee

Department of Biological Sciences

Pathogenicity of Pseudomonas aeruginosa, a major cause of many acute and chronic human infections, is determined by tightly regulated expression of multiple virulence factors. Quorum sensing (QS) controls expression of many of these pathogenic determinants. Previous microarray studies have shown that the AmpC β-lactamase regulator AmpR, a member of the LysR family of transcription factors, also controls non-β-lactam resistance and multiple virulence mechanisms. Using RNA-Seq and complementary assays, this study further expands the AmpR regulon to include diverse processes such as oxidative stress, heat shock and iron uptake. Importantly, AmpR affects many of these phenotypes, in part, by regulating expression …

Probiotics: Finding The Right Regulatory Balance, Diane E. Hoffmann, Claire M. Fraser-Liggett, Frank B. Palumbo, Jacques Ravel, Karen H. Rothenberg, Virginia Rowthorn

Faculty Scholarship

Some products marketed as drugs should be excused from Phase I trials, but safety and efficacy claims for dietary supplements should be more tightly regulated.

Membrane Vesicles Nucleate Mineralo-Organic Nanoparticles And Induce Carbonate Apatite Precipitation In Human Body Fluids, Cheng-Yeu Wu, Jan Martel, Wei-Yun Cheng, Chao-Chih He, David M. Ojcius, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Recent studies indicate that membrane vesicles (MVs) secreted by various cells are associated with human diseases, including arthritis, atherosclerosis, cancer, and chronic kidney disease. The possibility that MVs may induce the formation of mineralo-organic nanoparticles (NPs) and ectopic calcification has not been investigated so far. Here, we isolated MVs ranging in size between 20 and 400 nm from human serum and FBS using ultracentrifugation and sucrose gradient centrifugation. The MV preparations consisted of phospholipid-bound vesicles containing the serum proteins albumin, fetuin-A, and apolipoprotein A1; the mineralization-associated enzyme alkaline phosphatase; and the exosome proteins TNFR1 and CD63. Notably, we observed that …

The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-Beta Oligomer Toxicity, Valeriy G. Ostapchenko, Flavio H. Beraldo, Amro H. Mohammad, Yu-Feng Xie, Pedro H. F. Hirata, Ana C. Magalhaes, Guillaume Lamour, Hongbin Li, Andrzej Maciejewski, Jillian C. Belrose, Bianca L. Teixeira, Margaret Fahnestock, Sergio T. Ferreira, Neil R. Cashman, Glaucia N. M. Hajj, Michael F. Jackson, Wing-Yiu Choy, John F. Macdonald, Vilma R. Martins, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

In Alzheimer's disease (AD), soluble amyloid-beta oligomers (A beta Os) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrPC). However, it is unknown whether other ligands of PrPC can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrPC in the vicinity of the A beta O binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in A beta O toxicity. We confirmed the specific binding of A beta Os and STI1 to the PrP and showed that STI1 efficiently inhibited A …

Speed Is Relative (Human And Animal Running Speeds): Are You A Cheetah, A Chicken, Or A Snail?, Chad E. Buckley

Faculty and Staff Publications – Milner Library

To put matters in perspective, running speeds for humans and other land animals are compared over various distances. Humans compare quite favorably over longer distances with many species. Both fast and slow human runners can benefit from comparing their individual times in races with other species.

Social Compass Curriculum: Three Descriptive Case Studies Of Social Skills Outcomes For Students With Autism, Louanne E. Boyd, Deborah M. Ward

Engineering Faculty Articles and Research

The Social Compass Curriculum (SCC) was investigated for its effectiveness in improving core social skills in three descriptive case studies of students with autism. Treatment fidelity of the SCC was also measured in the school setting. The Social Responsiveness Scale and the Autism Social Skills Profile were completed by parents to measure pre- and postintervention social skills for three students aged 8 to 11 years who participated in the present multisite pilot study. Fidelity of implementation data were collected via a checklist during observations for three educators who implemented the intervention. Results indicate that the SCC improved core social deficits …

Involvement Of Reactive Oxygen Species In A Feed-Forward Mechanism Of Na/K-Atpase Mediated Signaling, Yanling Yan, Anna P. Shapiro, Steven Haller, Vinal Katragadda, Lijun Liu, Jiang Tian, Venkatesha Basrur, Deepak Malhotra, Zi-Jian Xie, Nader G. Abraham, Joseph I. Shapiro Md, Jiang Liu

Biochemistry and Microbiology

Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial ²²Na⁺ transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, …

Sex Differences In White Matter Development During Adolescence: A Dti Study, Yingying Wang, Chris Adamson, Weihong Yuan, Mekibib Altaye, Anna W. Byars, Scott K. Holland

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity …

Designer Babies: Why Not?, James Pierce

Explorer Café

No abstract provided.

Development Of A Conditional Mesd (Mesoderm Development) Allele For Functional Analysis Of The Low-Density Lipoprotein Receptor-Related Family In Defined Tissues, Andrew V. Taibi, Janet K. Lighthouse, Richard C. Grady, Kenneth R. Shroyer, Bernadette Holdener

Department of Biomedical Engineering Faculty Publications

The Low-density lipoprotein receptor-Related Protein (LRP) family members are essential for diverse processes ranging from the regulation of gastrulation to the modulation of lipid homeostasis. Receptors in this family bind and internalize a diverse array of ligands in the extracellular matrix (ECM). As a consequence, LRPs regulate a wide variety of cellular functions including, but not limited to lipid metabolism, membrane composition, cell motility, and cell signaling. Not surprisingly, mutations in single human LRPs are associated with defects in cholesterol metabolism and development of atherosclerosis, abnormalities in bone density, or aberrant eye vasculature, and may be a contributing factor in …

Identification Of Leptospira Interrogans Phospholipase C As A Novel Virulence Factor Responsible For Intracellular Free Calcium Ion Elevation During Macrophage Death, Jing-Fang Zhao, Hong-Hu Chen, David M. Ojcius, Xin Zhao, Dexter Sun, Yu-Mei Ge, Lin-Li Zheng, Xu'ai Lin, Lan-Juan Li, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Background: Leptospira-induced macrophage death has been confirmed to play a crucial role in pathogenesis of leptospirosis, a worldwide zoonotic infectious disease. Intracellular free Ca²⁺ concentration ([Ca²⁺]i) elevation induced by infection can cause cell death, but [Ca²⁺]i changes and high [Ca²⁺]i-induced death of macrophages due to infection of Leptospira have not been previously reported.

Methodology/Principal Findings: We first used a Ca²⁺-specific fluorescence probe to confirm that the infection of L. interrogans strain Lai triggered a significant increase of [Ca²⁺]i in mouse J774A.1 or human THP-1 macrophages. Laser confocal microscopic examination …

Small Molecule Antagonists Of Melanopsin-Mediated Phototransduction, Kenneth A. Jones, Megumi Hatori, Ludovic S. Mure, Jayne R. Bramley, Roman Artymyshyn, Sang-Phyo Hong, Mohammad Marzabadi, Huailing Zhong, Jeffrey Sprouse, Quansheng Zhu, Andrew T. E. Hartwick, Patricia J. Sollars, Gary E. Pickard, Satchidananda Panda

School of Veterinary and Biomedical Sciences: Faculty Publications

Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several CNS responses including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity. Novel sulfonamide compounds inhibiting melanopsin (opsinamides) compete with retinal binding to melanopsin and inhibit its function without affecting rod/cone mediated responses. In vivo administration of opsinamides to mice specifically and reversibly modified melanopsin-dependent light responses including the pupillary light reflex and …

The Mosakowski Institute For Public Enterprise Five Year Report, Mosakowski Institute

Mosakowski Institute for Public Enterprise

This report contains the highlights of the first five years of Clark University’s Mosakowski Institute for Public Enterprise. It includes a description of the Institute’s founding, its commitment to use-inspired research, transformational educational experiences, and community connectedness, the Institute’s leadership and finances, and a listing of projects undertaken and faculty partners.

2012-2013 Hccp Year-End Summary, Kristen S. Cloutier

Year-end Summaries

No abstract provided.

Comparison Of The Effect Of Caffeine Ingestion On Time To Exhaustion Between Endurance Trained And Untrained Men, Steven Porterfield, Jon Linderman, Lloyd L. Laubach, Corinne M. Daprano

Health and Sport Science Faculty Publications

This study compared the ergogenic effects of caffeine on men who were endurance trained to those who were untrained. The study was a double-blind, placebo-controlled crossover experimental design. Ten endurance trained men (mean age 24.4 ± 2.0 yrs, weight 79.4 ± 8.5 kg, predicted VO2 max 46.3 ± 1.8 mL·kg-1·min-1) and 10 untrained men (mean age 22.8 ± 1.9 yrs, weight 88.9 ± 9.9 kg, predicted VO2 max 37.6 ± 2.7 mL·kg-1·min-1) completed two cycle ergometer trials to exhaustion at 80% of their predicted workload max 30 min after ingesting either 5 mg·kg-1 of body weight of caffeine or a …

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 …

Tossing The Coin For Half Life, William L. Romine

Biological Sciences Faculty Publications

No abstract provided.

Combined Erp/Fmri Evidence For Early Word Recognition Effects In The Posterior Inferior Temporal Gyrus, Joseph Dien, Eric S. Brian, Dennis L. Molfese, Brian T. Gold

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Two brain regions with established roles in reading are the posterior middle temporal gyrus and the posterior fusiform gyrus. Lesion studies have also suggested that the region located between them, the posterior inferior temporal gyrus (pITG), plays a central role in word recognition. However, these lesion results could reflect disconnection effects since neuroimaging studies have not reported consistent lexicality effects in pITG. Here we tested whether these reported pITG lesion effects are due to disconnection effects or not using parallel ERP/fMRI studies. We predicted that the Recognition Potential (RP), a left-lateralized ERP negativity that peaks at about 200–250 ms, might …

A Miniaturised Spectrometer Device For The Detection Of Nitrogen Dioxide In An Urban Environment, Brian Devine

Doctoral

Monitoring of air pollutants, such as Nitrogen Dioxide (NO2), that are toxic or environmentally damaging is a key metric for environmental protection agencies worldwide. There is a constant need to develop new technologies and methodologies that provide real-time, low cost pollution measurements over a broad range of sampling sites, particularly in urban and industrial areas. Typically, detection of pollutants in urban environments is performed using a variety of techniques, many of which are expensive, require complex setups and are in fixed locations. The novel system presented in this thesis is designed for portable, low cost and in-situ detection of pollutants …

High Dose, Variable Length, N-Acetylcysteine (Hinac) Therapy For Late-Presenting Acetaminophen Poisoning, Jessica K. Eygnor Do, Suprina Dorai Md, Philip W. Moore Do, J Ward Donovan Md, Keith K. Burkhart Md

Department of Emergency Medicine

No abstract provided.

Synthesis And Antiproliferative Activities Of Quebecol And Its Analogs, Kasiviswanadharaju Pericherla, Amir Nasrolahi Shirazi, V. Kameshwara Rao, Rakesh Tiwari, Nicholas Dasilva, Kellen Mccaffrey, Yousef A. Beni, Antonio González- Sarrías, Navindra P. Seeram, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

Simple and efficient synthesis of quebecol and a number of its analogs was accomplished in five steps. The synthesized compounds were evaluated for antiproliferative activities against human cervix adenocarcinoma (HeLa), human ovarian carcinoma (SK-OV-3), human colon carcinoma (HT-29), and human breast adenocarcinoma (MCF-7) cancer cell lines. Among all the compounds, 7c, 7d, 7f, and 8f exhibited antiproliferative activities against four tested cell lines with inhibition over 80% at 75 mu M after 72 h, whereas, compound 7b and 7g were more selective towards MCF-7 cell line. The IC50 values for compounds 7c, 7d, and 7f were 85.1 mu M, 78.7 …

Differential Joint-Specific Corticospinal Tract Projections Within The Cervical Enlargement, Curtis O. Asante, John H. Martin

Publications and Research

The motor cortex represents muscle and joint control and projects to spinal cord interneurons and–in many primates, including humans–motoneurons, via the corticospinal tract (CST). To examine these spinal CST anatomical mechanisms, we determined if motor cortex sites controlling individual forelimb joints project differentially to distinct cervical spinal cord territories, defined regionally and by the locations of putative last-order interneurons that were transneuronally labeled by intramuscular injection of pseudorabies virus. Motor cortex joint-specific sites were identified using intracorticalmicrostimulation. CST segmental termination fields from joint-specific sites, determined using anterograde tracers, comprised a high density core of terminations that was consistent between animals …

Cholinergic Enhancement Of Brain Activation In Mild Cognitive Impairment During Episodic Memory Encoding, Shannon L. Risacher, Yang Wang, Heather A. Wishart, Laura A. Rabin, Laura A. Flashman, Brenna C. Mcdonald, John D. West, Robert B. Santulli, Andrew J. Saykin

Publications and Research

Objective: To determine the physiological impact of treatment with donepezil (Aricept) on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI) using functional magnetic resonance imaging (fMRI).

Methods: Eighteen patients with MCI and 20 age-matched healthy controls (HC) were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HCwere untreated but rescanned at the same interval.Voxel-level analyses assessed treatment effects on activation profiles in MCI patients relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry …

Forebrain Deletion Of The Vesicular Acetylcholine Transporter Results In Deficits In Executive Function, Metabolic, And Rna Splicing Abnormalities In The Prefrontal Cortex, Benjamin Kolisnyk, Mohammed A. Al-Onaizi, Pedro H. F. Hirata, Monica S. Guzman, Simona Nikolova, Shahar Barbash, Hermona Soreq, Robert Bartha, Marco A. M. Prado, Vania F. Prado

Anatomy and Cell Biology Publications

One of the key brain regions in cognitive processing and executive function is the prefrontal cortex (PFC), which receives cholinergic input from basal forebrain cholinergic neurons. We evaluated the contribution of synaptically released acetylcholine (ACh) to executive function by genetically targeting the vesicular acetylcholine transporter (VAChT) in the mouse forebrain. Executive function was assessed using a pairwise visual discrimination paradigm and the 5-choice serial reaction time task (5-CSRT). In the pairwise test, VAChT-deficient mice were able to learn, but were impaired in reversal learning, suggesting that these mice present cognitive inflexibility. Interestingly, VAChT-targeted mice took longer to reach criteria in …

The -9/+9 Polymorphism Of The Bradykinin Receptor Beta 2 Gene And Athlete Status: A Study Involving Two European Cohorts., Marek Sawczuk, Yevgeniya I. Timshina, Irina V. Astratenkova, Agnieszka Maciejewska-Karłowska, Agata Leońska-Duniec, Krzysztof Ficek, Leysan J. Mustafina, Paweł Cięszczyk, Tomasz Klocek, Ildus I. Ahmetov

Human Biology Open Access Pre-Prints

Background: Previous studies concerning the relevance of the BDKRB2 gene polymorphisms revealed that the absence (–9 allele) of a 9 base pair sequence in exon 1 of the BDKRB2 gene is correlated with higher skeletal muscle metabolic efficiency, glucose uptake during exercise, as well as endurance athletic performance. Aim: The aim of the study was to investigate the association between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of east-European athletes. Therefore, we examined the genotype distribution of the BDKRB2 9/+9 polymorphic site in a group of Polish athletes and confirmed the results obtained in a replication …

How Studies Of Human Sex Ratios At Birth May Lead To The Understanding Of Several Forms Of Pathology, William H. James

Human Biology Open Access Pre-Prints

This paper deals with the problem of the causes of the variation of sex ratio (proportion male) at birth. This problem is common to a number of areas in biology and medicine e.g. obstetrics, neurology/psychiatry, parasitology, virology, oncology and teratology. It is established that there are significantly biased, but unexplained, sex ratios in each of these fields. Yet workers in them (with the possible exception of virology) have regarded the problem as a minor loose end, irrelevant to the field’s major problems. However, as far as I know, no-one has previously noted that unexplained biased sex ratios occur, and thus …

Centrosomal Kinase Nek2 Cooperates With Oncogenic Pathways To Promote Metastasis, T K. Das, Dibyendu Dana, Suneeta S. Paroly, S. K. Perumal, S. Singh, H. Jhun, J. Pendse, R. L. Cagan, T. T. Talele, Sanjai Kumar

Publications and Research

Centrosomal kinase Nek2 is overexpressed in different cancers, yet how it contributes toward tumorigenesis remains poorly understood. dNek2 overexpression in a Drosophila melanogaster model led to upregulation of Drosophila Wnt ortholog wingless (Wg), and alteration of cell migration markers—Rho1, Rac1 and E-cadherin (Ecad)—resulting in changes in cell shape and tissue morphogenesis. dNek2 overexpression cooperated with receptor tyrosine kinase and mitogen-activated protein kinase signaling to upregulate activated Akt, Diap1, Mmp1 and Wg protein to promote local invasion, distant seeding and metastasis. In tumor cell injection assays, dNek2 cooperated with Ras and Src signaling to promote aggressive colonization of tumors into different …

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 …