Digital Commons Network^™

Insulin Resistance, Ceramide Accumulation, And Endoplasmic Reticulum Stress In Human Chronic Alcohol-Related Liver Disease, Lisa Longato, Kelsey Ripp, Mashiko Setshedi, Miroslav Dostalek, Fatemeh Akhlaghi, Mark Branda, Jack R. Wands, Suzanne M. De La Monte

Biomedical and Pharmaceutical Sciences Faculty Publications

Background. Chronic alcohol-related liver disease (ALD) is mediated by insulin resistance, mitochondrial dysfunction, inflammation, oxidative stress, and DNA damage. Recent studies suggest that dysregulated lipid metabolism with accumulation of ceramides, together with ER stress potentiate hepatic insulin resistance and may cause steatohepatitis to progress. Objective. We examined the degree to which hepatic insulin resistance in advanced human ALD is correlated with ER stress, dysregulated lipid metabolism, and ceramide accumulation. Methods. We assessed the integrity of insulin signaling through the Akt pathway and measured proceramide and ER stress gene expression, ER stress signaling proteins, and ceramide profiles in …

Community Annotation And Bioinformatics Workforce Development In Concert—Little Skate Genome Annotation Workshops And Jamborees, Qinghua Wang, Cecilia N. Arighi, Benjamin L. King, Shawn W. Polson, James Vincent, Chumching Chen, Hongzhan Huang, Brewster F. Kingham, Shallee T. Page, Marc Farnum Rendino, William Kelley Thomas, Daniel W. Udwary, Cathy H. Wu

Biomedical and Pharmaceutical Sciences Faculty Publications

Recent advances in high-throughput DNA sequencing technologies have equipped biologists with a powerful new set of tools for advancing research goals. The resulting flood of sequence data has made it critically important to train the next generation of scientists to handle the inherent bioinformatic challenges. The North East Bioinformatics Collaborative (NEBC) is undertaking the genome sequencing and annotation of the little skate (Leucoraja erinacea) to promote advancement of bioinformatics infrastructure in our region, with an emphasis on practical education to create a critical mass of informatically savvy life scientists. In support of the Little Skate Genome Project, the …

One-Pot Regioselective Synthesis Of Tetrahydroindazolones And Evaluation Of Their Antiproliferative And Src Kinase Inhibitory Activities, V. Kameshwara Rao, Bhupender S. Chhikara, Rakesh Tiwari, Amir Nasrolahi Shirazi, Keykavous Parang, Anil Kumar

Biomedical and Pharmaceutical Sciences Faculty Publications

A number of 2-substituted tetrahydroindazolones were synthesized by three-component condensation reaction of 1,3-diketones, substituted hydrazines, benzaldehydes, and Yb(OTf)₃ as a catalyst in [bmim][BF₄] ionic liquid using a simple, efficient, and economical one-pot method. The synthesized tetrahydroindazolones were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. 3,4-Dichlorophenyl tetrahydroindazolone derivative (15) inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 62% and 58%, respectively. 2,3-Diphenylsubstituted tetrahydroindazolone derivatives, 19, 25, and 33, inhibited the cell proliferation of HT-29 cells by 65–72% at a …

Antiamoebic Properties Of The Actinomycete Metabolites Echinomycin A And Tirandamycin A, Avelina Espinosa, Aaron M. Socha, Erica Ryke, David C. Rowley

Biomedical and Pharmaceutical Sciences Faculty Publications

Entamoeba histolytica infects 50 million people per year, causing 100,000 deaths worldwide. The primary treatment for amoebiasis is metronidazole. However, increased pathogen resistance combined with the drug’s toxic side effects encourages a search for alternative therapeutic agents. Secondary metabolites from marine bacteria are a promising resource for antiprotozoan drug discovery. In this study, extracts from a collection of marine-derived actinomycetes were screened for antiamoebic properties, and the activities of antibiotics echinomycin A and tirandamycin A are shown. Both antibiotics inhibited the in vitro growth of a E. histolytica laboratory strain (HM-1:IMSS) and a clinical isolate (Colombia, Col) at 30- to …

Dec1 Binding To The Proximal Promoter Of Cyp3a4 Ascribes To The Downregulation Of Cyp3a4 Expression By Il-6 In Primary Human Hepatocytes, Zhao Mao, Xiaofei Luan, Gang Cao, Wei Liu, Jing Xiong, Gang Hu, Ruini Chen, Rui Ning, Wei Shang, Jian Yang, Bingfang Yan

Biomedical and Pharmaceutical Sciences Faculty Publications

In this study, we provided molecular evidences that interleukin-6 (IL-6) contributed to the decreased capacity of oxidative biotransformation in human liver by suppressing the expression of cytochrome P450 3A4 (CYP3A4). After human hepatocytes were treated with IL-6, differentially expressed in chondrocytes 1 (DEC1) expression rapidly increased, and subsequently, the CYP3A4 expression decreased continuously. Furthermore, the repression of CYP3A4 by IL-6 occurred after the increase of DEC1 in primary human hepatocytes. In HepG2 cells, knockdown of DEC1 increased the CYP3A4 expression and its enzymatic activity. In addition, it partially abolished the decreased CYP3A4 expression as well as its enzymatic activity induced …

The Streptomycin-Treated Mouse Intestine Selects Escherichia Coli Envz Missense Mutants That Interact With Dense And Diverse Intestinal Microbiota, Mary P. Leatham-Jensen, Jakob Frimodt-Møller, Jimmy Adediran, Matthew E. Mokszycki, Megan E. Banner, Joyce E. Caughron, Karen A. Krogfelt, Tyrrell Conway, Paul S. Cohen

Cell and Molecular Biology Faculty Publications

Previously, we reported that the streptomycin-treated mouse intestine selected nonmotile Escherichia coli MG1655 flhDC deletion mutants of E. coli MG1655 with improved colonizing ability that grow 15% faster in vitro in mouse cecal mucus and 15 to 30% faster on sugars present in mucus (M. P. Leatham et al., Infect. Immun. 73:8039–8049, 2005). Here, we report that the 10 to 20% remaining motile E. coli MG1655 are envZ missense mutants that are also better colonizers of the mouse intestine than E. coli MG1655. One of the flhDC mutants, E. coli MG1655 ΔflhD, and one of the envZ missense …

Urinformed Spring 2012, Urinformed

URInformed: The URI Employees' Newsletter

No abstract provided.

Integration Of Genome-Wide Expression And Methylation Data: Relevance To Aging And Alzheimer's Disease, Hany Alashwal, Remi Dosunmu, Nasser H. Zawia

Biomedical and Pharmaceutical Sciences Faculty Publications

The progressive and latent nature of neurodegenerative diseases, such as Alzheimer's disease (AD) indicates the role of epigenetic modification in disease susceptibility. Previous studies from our lab show that developmental exposure to lead (Pb) perturbs the expression of AD-associated proteins. In order to better understand the role of DNA methylation as an epigenetic modifications mechanism in gene expression regulation, an integrative study of global gene expression and methylation profiles is essential. Given the different formats of gene expression and methylation data, combining these data for integrative analysis can be challenging. In this paper we describe a method to integrate and …

Developmental Exposure To Lead (Pb) Alters The Expression Of The Human Tau Gene And Its Products In A Transgenic Animal Model, M. Dash, A. Eid, G. Subaiea, J. Chang, R. Deeb, A. Masoud, William E. Renehan, A. Adem, Nasser H. Zawia

Biomedical and Pharmaceutical Sciences Faculty Publications

Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of the tau protein in the human brain. The best known of these illnesses is Alzheimer’s disease (AD); a disease where the microtubule associated protein tau (MAPT) becomes hyperphosphorylated (lowering its binding affinity to microtubules) and aggregates within neurons in the form of neurofibrillary tangles (NFTs). In this paper we examine whether environmental factors play a significant role in tau pathogenesis. Our studies were conducted in a double mutant mouse model that expressed the human tau gene and lacked the gene for murine tau. The human tau mouse …

Antioxidant Sulforaphane And Sensitizer Trinitrobenzene Sulfonate Induce Carboxylesterase-1 Through A Novel Element Transactivated By Nuclear Factor-E2 Related Factor-2, Yi-Tzai Chen, Deshi Shi, Dongfang Yang, Bingfang Yan

Biomedical and Pharmaceutical Sciences Faculty Publications

Carboxylesterase-1 (CES1), the most versatile human carboxylesterase, plays critical roles in drug metabolism and lipid mobilization. This enzyme is highly induced by antioxidants and sensitizers in various cell lines. These compounds are known to activate nuclear factor-E2 related factor-2 (Nrf2) by reacting to kelch-like ECH-associated protein-1 (Keap1). The aims of this study were to determine whether antioxidant sulforaphane (SFN) and sensitizer trinitrobenzene sulfonate (TNBS) target Keap1 similarly and whether they use the same element for CES1 induction. Cells over-expressing Keap1 were treated with TNBS or SFN and the formation of disulfide bonds among Keap1 molecules were determined. SFN promoted intramolecular …

Genome-Wide Expression And Methylation Profiling In The Aged Rodent Brain Due To Early-Life Pb Exposure And Its Relevance To Aging, Remi Dosunmu, Hany Alashwal, Nasser H. Zawia

Biomedical and Pharmaceutical Sciences Faculty Publications

In this study, we assessed global gene expression patterns in adolescent mice exposed to lead (Pb) as infants and their aged siblings to identify reprogrammed genes. Global expression on postnatal day 20 and 700 was analyzed and genes that were down- and up-regulated (≥2 fold) were identified, clustered and analyzed for their relationship to DNA methylation. About 150 genes were differentially expressed in old age. In normal aging, we observed an up-regulation of genes related to the immune response, metal-binding, metabolism and transcription/transduction coupling. Prior exposure to Pb revealed a repression in these genes suggesting that disturbances in developmental stages …

Combination Of Trail And Actinomycin D Liposomes Enhances Antitumor Effect In Non-Small Cell Lung Cancer, Liangran Guo, Li Fan, Jinfeng Ren, Zhiqing Pang, Yulong Ren, Jingwei Li, Ziyi Wen, Yong Qian, Lin Zhang, Hang Ma, Xinguo Jiang

Biomedical and Pharmaceutical Sciences Faculty Publications

The intractability of non-small cell lung cancer (NSCLC) to multimodality treatments plays a large part in its extremely poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cytokine for selective induction of apoptosis in cancer cells; however, many NSCLC cell lines are resistant to TRAIL-induced apoptosis. The therapeutic effect can be restored by treatments combining TRAIL with chemotherapeutic agents. Actinomycin D (ActD) can sensitize NSCLC cells to TRAIL-induced apoptosis by upregulation of death receptor 4 (DR4) or 5 (DR5). However, the use of ActD has significant drawbacks due to the side effects that result from its nonspecific biodistribution …

Modeling Range Dynamics In Heterogeneous Landscapes: Invasion Of The Hemlock Woolly Adelgid In Eastern North America, Matthew C. Fitzpatrick, Evan L. Preisser, Adam Porter, Joseph Elkinton, Aaron M. Ellison

Biological Sciences Faculty Publications

Range expansion by native and exotic species will continue to be a major component of global change. Anticipating the potential effects of changes in species distributions requires models capable of forecasting population spread across realistic, heterogeneous landscapes and subject to spatiotemporal variability in habitat suitability. Several decades of theory and model development, as well as increased computing power and availability of fine‐resolution GIS data, now make such models possible. Still unanswered, however, is the question of how well this new generation of dynamic models will anticipate range expansion. Here we develop a spatially explicit stochastic model that combines dynamic dispersal …

Algal Genomes Reveal Evolutionary Mosaicism And The Fate Of Nucleomorphs, Bruce A. Curtis, Christopher E. Lane, Et Al

Biological Sciences Faculty Publications

Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote–eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both …

Temperature Compensation Of Aerobic Capacity And Performance In The Antarctic Pteropod, Clione Antarctica, Compared With Its Northern Congener, C. Limacina, Agnieszka K. Dymowska, Thomas Manfredi, Joshua J. C. Rosenthal, Brad A. Seibel

Biological Sciences Faculty Publications

In ectotherms living in cold waters, locomotory performance is constrained by a slower generation of the ATP that is needed to fuel muscle contraction. Both polar and temperate pteropods of the genus Clione, however, are able to swim continuously by flapping their parapodia (wings) at comparable frequencies at their respective habitat temperatures. Therefore, we expected polar species to have increased aerobic capacities in their wing muscles when measured at common temperatures. We investigated muscle and mitochondrial ultrastructure of Clione antarctica from the Southern Ocean (−1.8°C) and populations of a sister species, Clione limacina, from the Arctic (−0.5 to …

Feeding In The Dark: Lateral-Line-Mediated Prey Detection In The Peacock Cichlid Aulonocara Stuartgranti, Margot A. B. Schwalbe, Daniel K. Bassett, Jacqueline F. Webb

Biological Sciences Faculty Publications

The cranial lateral line canal system of teleost fishes is morphologically diverse and is characterized by four patterns. One of these, widened lateral line canals, has evolved convergently in a wide range of teleosts, including the Lake Malawi peacock cichlids (Aulonocara), and has been attributed to its role in prey detection. The ability to study Aulonocara in the laboratory provides an opportunity to test the hypothesis that their reported ability to feed on invertebrate prey living in sandy substrates in their natural habitat is the result of lateral-line-mediated prey detection. The goal of this study was to determine …

Allocation Of Endogenous And Dietary Protein In The Reconstitution Of The Gastrointestinal Tract In Migratory Blackcaps At Stopover Sites, Agusti Muñoz-Garcia, Sarah Aamidor, Marshall D. Mccue, Scott R. Mcwilliams, Berry Pinshow

Natural Resources Science Faculty Publications

During migratory flight, the mass of the gastrointestinal tract (GIT) and its associated organs in small birds decreases in size by as much as 40%, compared with the preflight condition because of the catabolism of protein. At stopover sites, birds need 2–3 days to rebuild their GIT so that they can restore body mass and fat reserves to continue migration. The source of protein used to rebuild the GIT may be exogenous (from food ingested) or endogenous (reallocated from other organs) or both. Because the relative contribution of these sources to rebuild the GIT of migratory birds is not yet …

Tracking The Mind’S Eye: A New Technology For Researching Twenty-First-Century Writing And Reading Processes, Chris M. Anson, Robert A. Schwegler

Professional and Public Writing Faculty Publications

This article describes the nature of eye-tracking technology and its use in the study of discourse processes, particularly reading. It then suggests several areas of research incomposition studies, especially at the intersection of writing, reading, and digital media, that can benefit from the use of this technology.

Out Of Florida: Mtdna Reveals Patterns Of Migration And Pleistocene Range Expansion Of The Green Anole Lizard (Anolis Carolinensis), Shane C. Campbell-Staton, Rachel M. Goodman, Niclas Backström, Scott V. Edwards, Jonathan B. Losos, Jason J. Kolbe

Biological Sciences Faculty Publications

Anolis carolinensis is an emerging model species and the sole member of its genus native to the United States. Considerable morphological and physiological variation has been described in the species, and the recent sequencing of its genome makes it an attractive system for studies of genome variation. To inform future studies of molecular and phenotypic variation within A. carolinensis, a rigorous account of intraspecific population structure and relatedness is needed. Here, we present the most extensive phylogeographic study of this species to date. Phylogenetic analyses of mitochondrial DNA sequence data support the previous hypothesis of a western Cuban origin …

Vegetation And Invertebrate Community Response To Eastern Hemlock Decline In Southern New England, Laura L. Ingwell, Mailea Miller-Pierce, R. Talbot Trotter Iii, Evan L. Preisser

Biological Sciences Faculty Publications

The introduction of Adelges tsugae (Hemlock Woolly Adelgid [HWA]) to the eastern United States has had a devastating impact on Tsuga canadensis (Eastern Hemlock). Although much research has been done to assess HWA impacts on ecosystem processes and vegetation structure, few researchers have examined community-level changes in highly infested forest stands. Here we assess the impact of Eastern Hemlock mortality on vegetation and invertebrate diversity and community structure by comparing low-impact (healthy) stands and stands heavily impacted by HWA. We sampled the vegetative and invertebrate diversity of 8 sites (4 low impact and 4 high impact) in the summer and …

Inhibition Of Bacterial Growth And Biofilm Production By Constituents From Hypericum Spp., Simon A. Sarkisian, J. Janssen, H. Matta, G. E. Henry, Kerry L. Laplante, David C. Rowley

Pharmacy Practice and Clinical Research Faculty Publications

Biofilm embedded bacterial pathogens such as Staphylococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii are difficult to eradicate and are major sources of bacterial infections. New drugs are needed to combat these pathogens. Hypericum is a plant genus that contains species known to have antimicrobial properties. However, the specific constituents responsible for the antimicrobial properties are not entirely known, nor have most compounds been tested as inhibitors of biofilm development. The investigation presented here tested seven secondary metabolites isolated from the species Hypericum densiflorum, Hypericum ellipticum, Hypericum prolificum, and Hypericum punctatum as inhibitors of …

Manual And Electroacupuncture For Labour Pain: Study Design Of A Longitudinal Randomized Controlled Trial, Linda Vixner, Lena B. Mårtensson, Eliabet Stener-Victorin, Erica Schytt

College of Nursing Faculty Publications

Introduction. Results from previous studies on acupuncture for labour pain are contradictory and lack important information on methodology. However, studies indicate that acupuncture has a positive effect on women’s experiences of labour pain. The aim of the present study was to evaluate the efficacy of two different acupuncture stimulations, manual or electrical stimulation, compared with standard care in the relief of labour pain as the primary outcome. This paper will present in-depth information on the design of the study, following the CONSORT and STRICTA recommendations. Methods. The study was designed as a randomized controlled trial based on western …

Validation Of The Delinquent Activities Scale For Incarcerated Adolescents, Racheal Reavy, L.A.R. Stein, Andrea L. Paiva, Kathryn Quina, Joseph S. Rossi

Psychology Faculty Publications

Purpose: This study examined the validity of the Delinquent Activities Scale (DAS), based in part on the Self Reported Delinquency (SRD) scale.

Method: Participants were 190 incarcerated adolescents (85.8% male; average age 17 years) at a juvenile correctional facility in the Northeast. While incarcerated, they were asked about substance use and delinquent activities in the 1 year prior to incarceration, as well as parental, peer, and demographic information. They were tracked at three months post-release, given the DAS, and assessed for post-release substance use.

Results: Three factors of the DAS assess general, alcohol-involved, and marijuana-involved delinquent activities. Principal components analysis …

Aboard Gso: A Newsletter For Alumni And Friends Of The University Of Rhode Island’S Graduate School Of Oceanography For Fall 2012, Uri Graduate School Of Oceanography

Graduate School of Oceanography Publications

The Fall 2012 (Volume 10, Issue 1) issue of Aboard GSO: A Newsletter for Alumni and Friends of the University of Rhode Island’s Graduate School of Oceanography, a periodical about GSO events, faculty research and essays by alumni.

Fasting Serum C‐Peptide Levels Predict Cardiovascular And Overall Death In Nondiabetic Adults, Nileshkumar Patel, H. Taveira, Gaurav Choudhary, Hilary Whitlatch, Wen-Chih Wu

Pharmacy Practice and Clinical Research Faculty Publications

Background: Insulin resistance, characterized by hyperinsulinemia and normal or elevated serum glucose, is an established precursor to diabetes and cardiovascular disease. Despite fasting serum C‐peptide levels being an accurate and stable marker of endogenous insulin production used in patients with diabetes, it is unknown whether C‐peptide could serve as a marker of insulin resistance and predict outcomes in patients without diabetes.

Methods and Results: This is a retrospective cohort study using data from the NHANES‐3 (1988–1994) survey with mortality follow‐up through December 31, 2006. Participants included 5153 subjects, 40 to 74 years of age with fasting glucose ≥70 …

Organizational Characteristics Of High- And Low-Clozapine-Utilization Clinics In The Veterans Health Administration, Jessica L. Gören, J. Rose, Ryann L. Engle, Eric G. Smith, Melissa Christopher, Nathaniel M. Rickles, Todd P. Selma, Megan B. Mccullough

Pharmacy Practice and Clinical Research Faculty Publications

Objective: Treatment-resistance schizophrenia occurs in 20-30% of patients. Clozapine is the only medication proven effective for treatment-resistant schizophrenia. However, less than 25% of treatment-resistant schizophrenia patients receive clozapine in most settings. Therefore, this study was conducted to identify facilitators and barriers to clozapine use, to inform development of interventions to maximize appropriate clozapine-utilization.

Methods: Seventy semi-structured phone interviews were conducted with five high- and five low-utilization VA Medical Centers, from different US regions including urban and rural areas. Interviewees were key informants of clozapine processes, including mental health leadership, psychiatrists, clinical pharmacists and advanced practice nurses. Interviews were …

Efficient 18F-Labeling Of Large 37-Amino-Acid Phlip Peptide Analogues And Their Biological Evaluation, Pierre Daumar, Cindy A. Wanger-Baumann, Nagavarakishore Pillarsetty, Laura Fabrizio, Sean D. Carlin, Oleg A. Andreev, Yana K. Reshetnyak, Jason S. Lewis

Physics Faculty Publications

Solid tumors often develop an acidic microenvironment, which plays a critical role in tumor progression and is associated with increased level of invasion and metastasis. The 37-residue pH (low) insertion peptide (pHLIP) is under study as an imaging platform because of its unique ability to insert into cell membranes at a low extracellular pH (pH_e < 7). Labeling of peptides with [¹⁸F]-fluorine is usually performed via prosthetic groups using chemoselective coupling reactions. One of the most successful procedures involves the alkyne–azide copper(I) catalyzed cycloaddition (CuAAC). However, none of the known “click” methods have been applied to peptides as large as pHLIP. We designed a …

The Impact Of New Media On Intercultural Communication In Global Context, Guo-Ming Chen

Communication Studies Faculty Publications

The rapid development of new media has been the main force accelerating the trend of globalization in human society in recent decades. New media has brought human interaction and society to a highly interconnected and complex level, but at the same time challenges the very existence of intercultural communication in its traditional sense. It is under this circumstance that we see more and more scholars becoming involved in the investigation of the relationship between new media and intercultural communication. Emerging topical areas in this line of research mainly include three categories: (1) the impact of national/ethnic culture on the development …

Severe Diabetes And Leptin Resistance Cause Differential Hepatic And Renal Transporter Expression In Mice, Vijay More, Xia Wen, Paul E. Thomas, Lauren M. Aleksunes, Angela L. Slitt

Biomedical and Pharmaceutical Sciences Faculty Publications

Background: Type-2 Diabetes is a major health concern in the United States and other Westernized countries, with prevalence increasing yearly. There is a need to better model and predict adverse drug reactions, drug-induced liver injury, and drug efficacy in this population. Because transporters significantly contribute to drug clearance and disposition, it is highly significant to determine whether a severe diabetes phenotype alters drug transporter expression, and whether diabetic mouse models have altered disposition of acetaminophen (APAP) metabolites.

Results:

Transporter mRNA and protein expression were quantified in livers and kidneys of adult C57BKS and db/db mice, which have a …

Questioning Appropriation: Agency And Complicity In A Transnational Feminist Location Politics, Joe Parker

Journal of Feminist Scholarship

In feminist circles agency is often opposed to complicity and associated with resistance to sexism and patriarchy, yet such binary oppositions make the political stakes of their presumed boundaries difficult to interrogate. By bringing location politics into dialogue with agency theory, boundaries of same/Other and location categories may move from a naturalized ground for political work to the contested center of a politics of resistance. I follow a Foucauldian interpretation of agency to reconsider the ethico-politics of established divisions of self and Other both individually and in terms of social movements. By following Gayatri Spivak, Meyda Yeğenoğlu, and Chandra Mohanty's …