Digital Commons Network^™

Surface Decorated Gold Nanoparticles By Linear And Cyclic Peptides As Molecular Transporters, Amir Nasrolahi Shirazi, Rakesh Kumar Tiwari, Donghoon Oh, Brian Sullivan, Kellen Mccaffrey, Dindyal Mandal, Keykavous Parang

Biomedical and Pharmaceutical Sciences Faculty Publications

Gold nanoparticles (AuNPs) were synthesized in situ in a green and rapid method from the reaction of reducing linear and cyclic peptides containing tryptophan and lysine residues, (KW)₅ and cyclic [KW]₅, with an aqueous solution of HAuCl₄ and were evaluated as cellular nanodrug delivery systems. The cyclic or linear nature of the peptide was found to determine the morphology and size of the formed peptide-AuNPs and their in vitro molecular transporting efficiency. While cyclic [KW]₅-AuNPs formed sponge-like agglomerates, linear (KW)₅-AuNPs demonstrated ball-shaped structures. A comparative flow cytometry study showed that the cellular …

Effect Of Caloric Restriction And Ampk Activation On Hepatic Nuclear Receptor, Biotransformation Enzyme, And Transporter Expression In Lean And Obese Mice, Supriya R. Kulkarni, Jialin Xu, Ajay C. Donepudi, Wei Wei, Angela L. Slitt

Biomedical and Pharmaceutical Sciences Faculty Publications

Purpose: Fatty liver alters liver transporter expression. Caloric restriction (CR), the recommended therapy to reverse fatty liver, increases Sirtuin1 deacetylase activity in liver. This study evaluated whether CR and CR mimetics reversed obesity-induced transporter expression in liver and hepatocytes.

Methods: mRNA and protein expression was determined in adult lean (lean) and leptin-deficient obese (OB) mice fed ad libitum or placed on 40% (kCal) reduced diet. Hepatocytes were isolated from lean and OB mice, treated with AMP Kinase activators, and gene expression was determined.

Results: CR decreased Oatp1a1, Oatp1b2, and Abcb11 mRNA expression in lean, but not OB mice. CR increased …

Keap1 Knockdown Increases Markers Of Metabolic Syndrome After Long-Term High Fat Diet Feeding, Vijay R. More, Jialin Xu, Prajakta C. Shimpi, Clyde Belgrave, James P. Luyendyk, Masayuki Yamamoto, Angela L. Slitt

Biomedical and Pharmaceutical Sciences Faculty Publications

The nuclear factor E2-related factor 2 (Nrf2)–Kelch-like ECH-associated protein 1 (Keap1) pathway upregulates antioxidant and biotransformation enzyme expression to counter cellular oxidative stress. The contributions of Nrf2 to other cellular functions, such as lipid homeostasis, are emerging. This study was conducted to determine how enhanced Nrf2 activity influences the progression of metabolic syndrome with long-term high-fat diet (HFD) feeding. C57BL/6 and Keap1-knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight and white adipose tissue mass compared to C57BL/6 mice on HFD, along with increased inflammation and lipogenic gene …

Short-Term Treatment With Tolfenamic Acid Improves Cognitive Functions In Alzheimer's Disease Mice, Gehad M. Subaiea, Lina I. Adwan, Aseef H. Ahmed, Karen E. Stevens, Nasser H. Zawia

Biomedical and Pharmaceutical Sciences Faculty Publications

Tolfenamic acid lowers the levels of the amyloid precursor protein (APP) and amyloid beta (Aβ) when administered to C57BL/6 mice by lowering their transcriptional regulator specificity protein 1 (SP1). To determine whether changes upstream in the amyloidogenic pathway that forms Aβ plaques would improve cognitive outcomes, we administered tolfenamic acid for 34 days to hemizygous R1.40 transgenic mice. After the characterization of cognitive deficits in these mice, assessment of spatial learning and memory functions revealed that treatment with tolfenamic acid attenuated long-term memory and working memory deficits, determined using Morris water maze and the Y-maze. These improvements occurred within a …

Urinformed April 2013, Urinformed

URInformed: The URI Employees' Newsletter

No abstract provided.

Mechanistic Insights Into Isoform-Dependent And Species-Specific Regulation Of Bile Salt Export Pump By Farnesoid X Receptor, Xiulong Song, Yuan Chen, Leila Valanejad, Rajani Kaimal, Bingfang Yan, Matthew Stoner, Ruitang Deng

Biomedical and Pharmaceutical Sciences Faculty Publications

Expression of bile salt export pump (BSEP) is regulated by the bile acid/farnesoid X receptor (FXR) signaling pathway. Two FXR isoforms, FXRα1 and FXRα2, are predominantly expressed in human liver. We previously showed that human BSEP was isoform-dependently regulated by FXR and diminished with altered expression of FXRα1 and FXRα2 in patients with hepatocellular carcinoma. In this study, we demonstrate that FXRα1 and FXRα2 regulate human BSEP through two distinct FXR responsive elements (FXRE): IR1a and IR1b. As the predominant regulator, FXRα2 potently transactivated human BSEP through IR1a, while FXRα1 weakly transactivated human BSEP through a newly identified IR1b. Relative …

Synthesis Of Novel Ciprofloxacin Analogues And Evaluation Of Their Anti-Proliferative Effect On Human Cancer Cell Lines, Narva Suresh, Hunsur Nagendra Nagesh, Kondapalli V. G. C. Sekhar, Anil Kumar, Amir N. Shirazi, Keykavous Parang

Biomedical and Pharmaceutical Sciences Faculty Publications

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substituted piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized (¹H NMR, ¹³C NMR and LCMS) and evaluated for their inhibitory activity on the proliferation of human caucasian acute lymphoblastic leukemia cells (CCRF-CEM), breast adenocarcinoma cells (MDA-MB-468) and human colon carcinoma cells (HCT-116). Among all the synthesized ciprofloxacin analogues 3t at 50 μM showed comparable potency to doxorubicin (10 μM) in all three cell lines and 3j inhibited proliferation of MDA-MB-468 up to 35% selectively over other two cell lines.

[Refer to PDF for graphical abstract]

Carboxylesterase-2 Is A Highly Sensitive Target Of The Antiobesity Agent Orlistat With Profound Implications In The Activation Of Anticancer Prodrugs, Da Xiao, Deshi Shi, Dongfang Yang, Benjamin Barthel, Tad H. Koch, Bingfang Yan

Biomedical and Pharmaceutical Sciences Faculty Publications

Orlistat has been the most used anti-obesity drug and the mechanism of its action is to reduce lipid absorption by inhibiting gastrointestinal lipases. These enzymes, like carboxylesterases (CESs), structurally belong to the α/β hydrolase fold superfamily. Lipases and CESs are functionally related as well. Some CESs (e.g., human CES1) have been shown to hydrolyze lipids. This study was designed to test the hypothesis that orlistat inhibits CESs with higher potency toward CES1 than CES2, a carboxylesterase with little lipase activity. Liver microsomes and recombinant CESs were tested for the inhibition of the hydrolysis of standard substrates and the anticancer prodrugs …

Impairment Of Trkb-Psd-95 Signaling In Angelman Syndrome, Cong Cao, Mengia S. Rioult-Pedotti, Paolo Migani, Crystal J. Yu, Rakesh Tiwari, Keykavous Parang, Mark R. Spaller, Dennis J. Goebel, John Marshall

Biomedical and Pharmaceutical Sciences Faculty Publications

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletalassociated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) …

Ventilation Rates And Activity Levels Of Juvenile Jumbo Squid Under Metabolic Suppression In The Oxygen Minimum Zone, Katja Trübenbach, Maria R. Pegado, Brad A. Seibel, Rui Rosa

Biological Sciences Faculty Publications

The Humboldt (jumbo) squid, Dosidicus gigas, is a part-time resident of the permanent oxygen minimum zone (OMZ) in the Eastern Tropical Pacific and, thereby, it encounters oxygen levels below its critical oxygen partial pressure. To better understand the ventilatory mechanisms that accompany the process of metabolic suppression in these top oceanic predators, we exposed juvenile D. gigas to the oxygen levels found in the OMZ (1% O₂, 1 kPa, 10°C) and measured metabolic rate, activity cycling patterns, swimming mode, escape jet (burst) frequency, mantle contraction frequency and strength, stroke volume and oxygen extraction efficiency. In normoxia, metabolic …

Colony Growth Of Corals Transplanted For Restoration Depends On Their Site Of Origin And Environmental Factors, Graham E. Forrester, Kerianne Taylor, Stephanie Schofield, Amy Maynard

Natural Resources Science Faculty Publications

We determined that growth differences among coral fragments transplanted for restoration were influenced by both source population and environmental factors. In two common garden experiments, storm-generated fragments of Acropora palmata were transplanted from two source populations in the British Virgin Islands to a restoration site (a “common garden”) that lacked A. palmata. In the first experiment, colonies from different sources grew at different rates in the first year after transplanting, suggesting either genetic differences among source populations or enduring acclimation to conditions at the source site. No differences in growth among source populations were detected in the second common garden …

Caribbean Damselfish Recolonize Reefs Following Coral Restoration, Sarah A. Merolla, Allison J. Holevoet, Samantha L. Musser, Graham E. Forrester

Natural Resources Science Faculty Publications

No abstract provided.

Theorizing Intercultural Adaptation From The Perspective Of Boundary Game, Guo-Ming Chen

Communication Studies Faculty Publications

The impact of globalization on human society strongly demands a constructive process of intercultural adaptation and a more systematic study of the concept. In order to tackle the problem of conceptual ambiguity in the existing literature, this analytical paper attempts to lay down the conceptual foundation by theorizing intercultural adaptation as a boundary game after a brief review of the previous literature. Intercultural adaptation as a boundary game is further supported by the argument that the boundary game of intercultural adaptation must be treated as totality. The author then advocates “boundary wisdom” as the key to the success of achieving …

Should Coral Fragments Collected For Restoration Be Subdivided To Create More, Smaller Pieces For Transplanting?, Graham E. Forrester, Russell P. Dauksis, Megan A. Ferguson

Natural Resources Science Faculty Publications

No abstract provided.

Multiple Environmental Chemical Exposures To Lead, Mercury And Polychlorinated Biphenyls Among Childbearing-Aged Women (Nhanes 1999–2004): Body Burden And Risk Factors, Marcella Remer Thompson, Kim Boekelheide

College of Nursing Faculty Publications

Background: Lead, mercury and polychlorinated biphenyls (PCBs) are neurotoxicants with intergenerational health consequences from maternal body burden and gestational exposures. Little is known about multiple chemical exposures among childbearing-aged women.

Objectives: To determine the percentage of women aged 16–49 of diverse races and ethnicities whose body burdens for all three xenobiotics were at or above the median; to identify mixed exposures; and to describe those women disproportionately burdened by two or more of these chemicals based on susceptibility- and exposure-related attributes, socioeconomic factors and race-ethnicity.

Methods: Secondary data analysis of National Health and Nutrition Examination Survey (1999–2004).

Results: The best-fit …

Aboard Gso: A Newsletter For Alumni And Friends Of The University Of Rhode Island’S Graduate School Of Oceanography For Summer 2013, Uri Graduate School Of Oceanography

Graduate School of Oceanography Publications

The Summer 2013 (Volume 11, 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.

Global Dynamics Of Three Anticompetitive Systems Of Difference Equations In The Plane, M. Dipippo, Mustafa Kulenovic

Mathematics Faculty Publications

We investigate the global dynamics of several anticompetitive systems of rational difference equations which are special cases of general linear fractional system of the forms

Χ_n+1 = (α₁ + β₁ χ_n + y₁y_n)(A₁ + B₁x_n + C₁y_n), y_n+1 = (α2 + β₂x_n + y₂y_n)/(A₂ + B₂x_n + C₂y_n), n = 0, 1,…, where all parameters and the initial conditions x₀, y_{0 …}

Phlip Peptide Targets Nanogold Particles To Tumors, Lan Yao, Jennifer Daniels, Anna Moshnikova, Sergey Kuznetsov, Aftab Ahmed, Donald M. Engelman, Yana Reshetnyak, Oleg A. Andreev

Physics Faculty Publications

Progress in nanomedicine depends on the development of nanomaterials and targeted delivery methods. In this work, we describe a method for the preferential targeting of gold nanoparticles to a tumor in a mouse model. The method is based on the use of the pH Low Insertion Peptide (pHLIP), which targets various imaging agents to acidic tumors. We compare tumor targeting by nonfunctionalized nanogold particles with nanogold–pHLIP conjugates, where nanogold is covalently attached to the N terminus of pHLIP. Our most important finding is that both intratumoral and i.v. administration demonstrated a significant enhancement of tumor uptake of gold nanoparticles conjugated …

Antiproliferative Effect Of Phlip-Amanitin, Anna Moshnikova, Valentina Moshnikova, Oleg A. Andreev, Yana Reshetnyak

Physics Faculty Publications

Toxins could be effective anticancer drugs, if their selective delivery into cancer cells could be achieved. We have shown that the energy of membrane-associated folding of water-soluble membrane peptides of the pHLIP (pH low insertion peptide) family could be used to move cell-impermeable cargo across the lipid bilayer into the cytoplasm of cancer cells. Here we present the results of a study of pHLIP-mediated cellular delivery of a polar cell-impermeable toxin, α-amanitin, an inhibitor of RNA polymerase II. We show that pHLIP can deliver α-amanitin into cells in a pH-dependent fashion and induce cell death within 48 h. Translocation capability …

Inclusion And Exclusion In Some Feminist Utopian Fictions, Karen F. Stein

English and Creative Writing Faculty Publications

No abstract provided.

Enhanced Taupathy And Ad-Like Pathology In Aged Primate Brains Decades After Infantile Exposure To Lead (Pb), Syed Waseem Bihaqi, Nasser H. Zawia

Biomedical and Pharmaceutical Sciences Faculty Publications

Late Onset Alzheimer Disease (LOAD) constitutes the majority of AD cases (∼90%). Amyloidosis and tau pathology, which are present in AD brains, appear to be sporadic in nature. We have previously shown that infantile lead (Pb) exposure is associated with a change in the expression and regulation of the amyloid precursor protein (APP) and its beta amyloid (Aβ) products in old age. Here we report that infantile Pb exposure elevated the mRNA and protein levels of tau as well as its transcriptional regulators namely specificity protein 1 and 3 (Sp1 and Sp3) in aged primates. These changes were also accompanied …

Urinformed Fall 2013, Urinformed

URInformed: The URI Employees' Newsletter

No abstract provided.

Annual Report Honors Program And Visiting Scholars Committee 2012-2013, University Of Rhode Island Faculty Senate

Faculty Senate Committee Reports and Appendices

No abstract provided.

Regulation Of Hemolysin Gene Expression And The Effects Of Metabolism Mutations On The Virulence Of Vibrio Anguillarum, Xiangyu Mou

Open Access Dissertations

Vibrio anguillarum is the causative agent of vibriosis, a fatal hemorrhagic septicemic disease. V. anguillarum infects more than 50 fresh and salt-water fish species including various species of economic importance to the larviculture and aquaculture industry. In vibriosis, V. anguillarum invades its host fish through the intestine and skin. Infected fish usually die with systemic infection of V. anguillarum. Bacterial hemolysins are exotoxins that cause lysis of erythrocytes in the host and thus the release of the intracellular heme, and are therefore identified as important virulence factors. Moreover, hemolysins are known to also cause lysis in other cell types, …

Population Vulnerability To Biannual Cholera Outbreaks And Associated Macro-Scale Drivers In The Bengal Delta, Ali Shafqat Akanda, Antarpreet S. Jutla, David M. Gute, R. Bradley Sack, Munirul Alam, Anwar Huq, Rita R. Colwell, Shafiqul Islam

Civil & Environmental Engineering Faculty Publications

The highly populated floodplains of the Bengal Delta have a long history of endemic and epidemic cholera outbreaks, both coastal and inland. Previous studies have not addressed the spatio-temporal dynamics of population vulnerability related to the influence of underlying large-scale processes. We analyzed spatial and temporal variability of cholera incidence across six surveillance sites in the Bengal Delta and their association with regional hydroclimatic and environmental drivers. More specifically, we use salinity and flood inundation modeling across the vulnerable districts of Bangladesh to test earlier proposed hypotheses on the role of these environmental variables. Our results show strong influence of …

Effects Of Ciona Intestinalis Distal-Less-B Nonexpression And Overexpression On Phenotype And Downstream Targets, Matthew David Blanchette

Open Access Dissertations

Ciona intestinalis can serve as a useful model for developmental studies in the chordate lineage due to its basal position in the chordate phylogeny. It shows a simplified chordate body plan during its development, during which important genetic pathways are conserved with vertebrates, and its developmental gene regulation can be manipulated through the insertion of transgenic DNA by electroporation. The Distalless (Dll) genes are a family of homeobox genes in chordates that are homologous to the single Dll gene of other metazoan animal groups and code for developmental factors that play a role in determining multiple developmental cell fates. These …

On Design And Implementation Of An Embedded System For Neural-Machine Interface For Artificial Legs, Xiaorong Zhang

Open Access Dissertations

According to limb loss statistics, there are over one million leg amputees in the US whose lives are severely impacted by their conditions. In order to improve the quality of life of patients with leg amputations, neural activities have been studied by many researchers for intuitive prosthesis control. The neural signals collected from muscles are electromyographic (EMG) signals, which represent neuromuscular activities and are effective bioelectrical signals for expressing movement intent. EMG pattern recognition (PR) is a widely used method for characterizing EMG signals and classifying movement intent. The key to the success of neural-controlled artificial limbs is the neural-machine …

Assessment Of Mammal Biodiversity In Coffee-Dominated Landscapes Of India And Costa Rica, Stephanie Amanda Caudill

Open Access Dissertations

The fate of many tropical wildlife species depends on the way in which human-dominated landscapes are managed. Conservation strategies that incorporate agricultural landscapes are imperative for the survival of native fauna. Coffee is a major cash crop worldwide and is grown in tropical regions of the world that are often designated as biodiversity hotspots. Shade coffee, an agroforestry system in which coffee is grown under the shade of intentionally managed and/or native tree cover, has shown promise to provide habitat and support the diversity of bird, bat, and insect communities, but few studies have focused on non-volant mammals living in …

Ultra-Low Power Pll Design And Jitter Anaylsis, Fu Luo

Open Access Dissertations

This thesis presents the design of ultra-low power Phase-Locked Loops (PLLs) intended for applications in the extended audio range. The PLL is well suited for battery operated systems, where small size and low power operation are crucially important. The two implementations presented are based on current controlled relaxation oscillator and a ring oscillator intended for the same frequency range. The frequency is controlled by a current that can vary from 2 to 74 nA. Using a reference frequency of ¼ of the typical watch crystal frequency, the user can select any integer multiple of 8.192 kHz up to the maximum …

Sustaining Environmental Flows In Southern New England Rivers: Effects Of Watreshed Factors And Land Use, Alisa Morrison

Open Access Dissertations

Rivers and river systems serve as conduits for nutrients and organisms, function as corridors for fish and wildlife passage, and provide resources for humans. Streamflow has been called the master variable in a river because it affects habitat diversity and availability through its impact on physical factors that influence habitat quality. However, land use changes such as urbanization and irrigation, can have major effects on stream hydrology. Modifications of the land surface due to urbanization alters natural stream hydrographs by increasing flood peaks, decreasing time to peak flows, and causing higher runoff velocities. Irrigation may produce the opposite effects.

In …