Digital Commons Network^™

Membrane Anchor R9ap Potentiates Gtpase-Accelerating Protein Activity Of Rgs11·Gβ5 Complex And Accelerates Inactivation Of The Mglur6-G0 Signaling, Ikuro Masuho, Jeremy Celver, Abraham Kovoor, Kirill A. Martemyanov

Biomedical and Pharmaceutical Sciences Faculty Publications

The R7 subfamily of RGS proteins critically regulates neuronal G protein-signaling pathways that are essential for vision, nociception, motor coordination, and reward processing. A member of the R7 RGS family, RGS11, is a GTPase-accelerating protein specifically expressed in retinal ON-bipolar cells where it forms complexes with the atypical G protein β subunit, Gβ₅, and transmembrane protein R9AP. Association with R9AP has been shown to be critical for the proteolytic stability of the complex in the retina. In this study we report that R9AP can in addition stimulate the GTPase-accelerating protein activity of the RGS11·Gβ₅ complex at Gα …

Rational Quantitative Structure–Activity Relationship (Rqsar) Screen For Pxr And Car Isoform-Specific Nuclear Receptor Ligands, Ann M. Dring, Linnea E. Anderson, Saima Qamar, Matthew A. Stoner

Biomedical and Pharmaceutical Sciences Faculty Publications

Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are closely related orphan nuclear receptor proteins that share several ligands and target overlapping sets of genes involved in homeostasis and all phases of drug metabolism. CAR and PXR are involved in the development of certain diseases, including diabetes, metabolic syndrome and obesity. Ligand screens for these receptors so far have typically focused on steroid hormone analogs with pharmacophore-based approaches, only to find relatively few new hits. Multiple CAR isoforms have been detected in human liver, with the most abundant being the constitutively active reference, CAR1, and the ligand-dependent isoform CAR3. …

Gender And Women's Studies Newsletter For Fall 2010, Uri Gender And Women's Studies Department

Gender and Women's Studies Publications

The Fall 2010 issue of Gender and Women’s Studies Newsletter, a periodical with articles written by faculty members and some related to events within the Gender and Women’s Studies program.

KV4.2 Channels Tagged In The S1-S2 Loop For Alpha-Bungarotoxin Binding Provide A New Tool For Studies Of Channel Expression And Localization, Leonard Moise, Jing Liu, Evgeny Pryazhnikov, Leonard Khiroug, Andreas Jeromin, Edward Hawrot

Cell and Molecular Biology Faculty Publications

We report the first successful insertion of an engineered, high-affinity alpha-bungarotoxin (Bgtx) binding site into a voltage-gated ion channel, K_V4.2, using a short, intra-protein embedded sequence (GGWRYYESSLEPYPDGG), derived from a previously described mimotope peptide, HAP. A major benefit to this approach is the ability to live-image the distribution and fate of functional channels on the plasma membrane surface. The Bgtx binding sequence was introduced into the putative extracellular loop between the S1 and S2 transmembrane domains of K_V4.2. Following co-expression with KChIP3 in tsA201 cells, S1-S2 HAP-tagged channels express at levels comparable to wild-type K_{V …}

Marine Reserves As Linked Social–Ecological Systems, Richard Pollnac, Patrick Christie, Joshua E. Cinner, Tracey Dalton, Tim M. Daw, Graham E. Forrester, Nicholas A. J. Graham, Timothy R. Mcclanahan

Marine Affairs Faculty Publications

Marine reserves are increasingly recognized as having linked social and ecological dynamics. This study investigates how the ecological performance of 56 marine reserves throughout the Philippines, Caribbean, and Western Indian Ocean (WIO) is related to both reserve design features and the socioeconomic characteristics in associated coastal communities. Ecological performance was measured as fish biomass in the reserve relative to nearby areas. Of the socioeconomic variables considered, human population density and compliance with reserve rules had the strongest effects on fish biomass, but the effects of these variables were region specific. Relationships between population density and the reserve effect on fish …

New Media And Cultural Identity In The Global Society, Guo-Ming Chen, Kai Zhang

Communication Studies Faculty Publications

New media has been the main force accelerating the development of globalizing society in the last two decades. With its digital, convergent, interactive, hypertextual, and virtual nature, new media has brought human interaction and society to a highly interconnected and complex level. The rapid transformation of human society due to the impact of the convergence of new media and globalization directly influences the construction and development of cultural identity. The emergence of new media and globalization not only breaks through the limit of the traditional time and space, but also may challenge the meaning of cultural identity. The purpose of …

Synthesis, Antiviral And Contraceptive Activities Of Nucleoside–Sodium Cellulose Sulfate Acetate And Succinate Conjugates, Hitesh K. Agarwal, Anil Kumar, Gustavo F. Doncel, Keykavous Parang

Biomedical and Pharmaceutical Sciences Faculty Publications

Chemical conjugates between sodium cellulose sulfate (CS), displaying contraceptive and HIV-entry inhibiting properties, and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), or 2′,3′-dideoxy-3′-thiacytidine (3TC)) were designed to simultaneously provide contraceptive and anti-HIV activity. Two linkers, acetate and succinate, were used to conjugate the nucleoside analogs with CS. The conjugates containing cellulose sulfate-acetate (CSA) (e.g., AZT–CSA and FLT–CSA) were found to be more potent than CS and other conjugates (e.g., AZT–succinate–CS, and FLT–succinate–CS). The presence of both sulfate and the acetate groups on cellulose were critical for generating maximum anti-HIV activity. In addition to showing equal potency against wild-type …

Pregnane X Receptor Is Required For Interleukin-6-Mediated Down-Regulation Of Cytochrome P450 3a4 In Human Hepatocytes, Jian Yang, Chunshu Hao, Dongfang Yang, Deshi Shi, Xiulong Song, Xiaofei Luan, Gang Hu, Bingfang Yan

Biomedical and Pharmaceutical Sciences Faculty Publications

Cytochrome P450 3A4 (CYP3A4) is the most abundant cytochrome P450 enzyme in human liver and metabolizes more than 60% of prescribed drugs in human body. Patients with liver conditions such as cirrhosis show increased secretion of cytokines (e.g., interleukin-6) and decreased capacity of oxidation of many drugs. In this study, we provided molecular evidence that cytokine secretion directly contributed to the decreased capacity of oxidative biotransformation in human liver. After human hepatocytes were treated with IL-6, the expression of CYP3A4 decreased at both mRNA and protein levels, so did the CYP3A4 enzymatic activity. Meanwhile, the repression of CYP3A4 by IL-6 …

Effects Of Hemlock Woolly Adelgid And Elongate Hemlock Scale On Eastern Hemlock Growth And Foliar Chemistry, Mailea R. Miller-Pierce, David A. Orwig, Evan L. Preisser

Biological Sciences Faculty Publications

In the eastern United States, two invasive specialist insects share a native host plant, Eastern hemlock, Tsuga canadensis. In recent years, much research has focused on the impacts of the hemlock woolly adelgid (Adelges tsugae) because of the detrimental effects it has on hemlock growth and survival. In contrast, the invasive elongate hemlock scale (Fiorinia externa) is thought to have only minor impacts on hemlock. We infested hemlock saplings with each insect and compared them with control (i.e., neither insect herbivore) saplings to assess how early infestations impact Eastern hemlock health (measured using new branch …

The Chitobiose Transporter, Chbc, Is Required For Chitin Utilization In Borrelia Burgdorferi, Ryan G. Rhodes, Janet A. Atoyan, David R. Nelson

Cell and Molecular Biology Faculty Publications

Background

The bacterium Borrelia burgdorferi, the causative agent of Lyme disease, is a limited-genome organism that must obtain many of its biochemical building blocks, including N-acetylglucosamine (GlcNAc), from its tick or vertebrate host. GlcNAc can be imported into the cell as a monomer or dimer (chitobiose), and the annotation for several B. burgdorferi genes suggests that this organism may be able to degrade and utilize chitin, a polymer of GlcNAc. We investigated the ability of B. burgdorferi to utilize chitin in the absence of free GlcNAc, and we attempted to identify genes involved in the process. We also examined …

Using Molecular-Assisted Alpha Taxonomy To Better Understand Red Algal Biodiversity In Bermuda, Elisabeth N. Cianciola, Thea R. Popolizio, Craig W. Schneider, Christopher E. Lane

Biological Sciences Faculty Publications

Molecular-assisted alpha taxonomy has recently become an effective practice in reassessing biodiversity and floristics for a variety of different organisms. This paper presents a series of examples that have been drawn from biodiversity work being carried out on the marine red algae of Bermuda. Molecular sequencing of DNA from Bermuda samples has already begun to greatly alter the makeup of the flora as it was known just decades ago, and will help set a new database for future comparison as climate change affects species composition in the islands.

Hybridization Of Invasive Phragmites Australis With A Native Subspecies In North America, Laura A. Meyerson, David V. Viola, Rebecca N. Brown

Natural Resources Science Faculty Publications

Interspecific hybridization can lead to the extinction of native populations and increased aggressiveness in hybrid forms relative to their parental lineages. However, interbreeding among subspecies is less often recognized as a serious threat to native species. Phragmites australis offers an excellent opportunity to investigate intraspecific hybridization since both native and introduced lineages occur in North America. Introduced Phragmites is a highly successful estuarine plant invader throughout North America, but native Phragmites populations are declining in the eastern US. Despite range overlaps, hybridization has not yet been detected between the native and introduced lineages in the wild, suggesting that phenological or …

Nuchal Cord Management And Nurse-Midwifery Practice, Judith S. Mercer, Rebecca L. Skovgaard, Joann Peareara-Eaves, Tracey A. Bowman

College of Nursing Faculty Publications

Nuchal cord, or cord around the neck of an infant at birth, is a common finding that has implications for labor, management at birth, and subsequent neonatal status. A nuchal cord occurs in 20% to 30% of births. All obstetric providers need to learn management techniques to handle the birth of an infant with a nuchal cord. Management of a nuchal cord can vary from clamping the cord immediately after the birth of the head and before the shoulders to not clamping at all, depending on the provider's learned practices. Evidence for specific management techniques is lacking. Cutting the umbilical …

Research & Innovation For 2009-2010, University Of Rhode Island

Publications (Research and Economic Development)

The 2009-2010 issue of Research & Innovation, a periodical focused on research at the University of Rhode Island.

Ph-(Low)-Insertion-Peptide (Phlip) Translocation Of Membrane Impermeable Phalloidin Toxin Inhibits Cancer Cell Proliferation, Ming An, Dayanjali Wijesinghe, Oleg A. Andreev, Yana K. Reshetnyak, Donald M. Engelman

Physics Faculty Publications

We find that pH-(low)-insertion-peptide (pHLIP)-facilitated translocation of phalloidin, a cell-impermeable polar toxin, inhibits the proliferation of cancer cells in a pH-dependent fashion. The monomeric pHLIP inserts its C terminus across a membrane under slightly acidic conditions (pH 6–6.5), forming a transmembrane helix. The delivery construct carries phalloidin linked to its inserting C terminus via a disulfide bond that is cleaved inside cells, releasing the toxin. To facilitate delivery of the polar agent, a lipophilic rhodamine moiety is also attached to the inserting end of pHLIP. After a 3 h incubation at pH 6.1–6.2 with 2–4 μM concentrations of the …

Ph (Low) Insertion Peptide (Phlip) Inserts Across A Lipid Bilayer As A Helix And Exits By A Different Path, Oleg A. Andreev, Alexander G. Karabadzhak, Dhammika Weerakkody, Gregory O. Andreev, Donald M. Engelman, Yana K. Reshetnyak

Physics Faculty Publications

What are the molecular events that occur when a peptide inserts across a membrane or exits from it? Using the pH-triggered insertion of the pH low insertion peptide to enable kinetic analysis, we show that insertion occurs in several steps, with rapid (0.1 sec) interfacial helix formation, followed by a much slower (100 sec) insertion pathway to give a transmembrane helix. The reverse process of unfolding and peptide exit from the bilayer core, which can be induced by a rapid rise of the pH from acidic to basic, proceeds approximately 400 times faster than folding/insertion and through different intermediate states. …

Ph-Sensitive Membrane Peptides (Phlips) As A Novel Class Of Delivery Agents, Oleg A. Andreev, Donald M. Engelman, Yana K. Reshetnyak

Physics Faculty Publications

Here we review a novel class of delivery vehicles based on pH-sensitive, moderately polar membrane peptides, which we call pH (Low) Insertion Peptides (pHLIPs), that target cells located in the acidic environment found in many diseased tissues, including tumours. Acidity targeting by pHLIPs is achieved as a result of helix formation and transmembrane insertion. In contrast to the earlier technologies based on cell-penetrating peptides, pHLIPs act as monomeric membrane-inserting peptides that translocate one terminus across a membrane into the cytoplasm, while the other terminus remains in the extracellular space, locating the peptide in the membrane lipid bilayer. Therefore pHLIP has …

Tuning The Insertion Properties Of Phlip, Monka Musial-Siwek, Alexander Karabadzhak, Oleg A. Andreev, Yana K. Reshetnyak, Donald M. Engelman

Physics Faculty Publications

The pH (low) insertion peptide (pHLIP) has exceptional characteristics: at neutral pH it is an unstructured monomer in solution or when bound to lipid bilayer surfaces, and it inserts across a lipid bilayer as a monomeric alpha-helix at acidic pH. The peptide targets acidic tissues in vivo and may be useful in cancer biology for delivery of imaging or therapeutic molecules to acidic tumors. To find ways to vary its useful properties, we have designed and analyzed pHLIP sequence variants. We find that each of the Asp residues in the transmembrane segment is critical for solubility and pH-dependent membrane insertion …

Solid-Phase Synthesis Of 5′-O-Β,Γ-Methylenetriphosphate Derivatives Of Nucleosides And Evaluation Of Their Inhibitory Activity Against Hiv-1 Reverse Transcriptase, Yousef Ahmadibeni, Chandravanu Dash, Stuart F.J. Le Grice, Keykavous Parang

Biomedical and Pharmaceutical Sciences Faculty Publications

Bis(dichlorophosphino)methane was converted to a β,γ-methylenetriphosphitylating reagent. The reagent was immobilized on aminomethyl polystyrene resin-bound linker of 4-acetoxy-3-phenylbenzyl alcohol to afford a polymer-bound β,γ-methylenetriphosphitylating reagent, which was reacted with unprotected nucleosides followed by oxidation with tert-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and acidic cleavage to produce 5′-O-β,γ-methylene triphosphate nucleosides in 53–82% overall yields. Among all the compounds, cytidine 5′-O-β,γ-methylenetriphosphate inhibited completely RNase H activity of HIV-1 reverse transcriptase at 700 μM.

[Refer to PDF for graphical abstract]

Partitioning Of Perfluorooctanoate Into Phosphatidylcholine Bilayers Is Chain Length-Independent, Wei Xie, Geoffrey D. Bothun, Hans-Joachim Lehmler

Chemical, Biomolecular, and Materials Engineering Faculty Publications

The chain length dependence of the interaction of PFOA, a persistent environmental contaminant, with dimyristoyl- (DMPC), dipalmitoyl- (DPPC) and distearoylphosphatidylcholine (DSPC) was investigated using steady-state fluorescence anisotropy spectroscopy, differential scanning calorimetry (DSC) and dynamic light scattering (DLS). PFOA caused a linear depression of the main phase transition temperature T_m while increasing the width of the phase transition of all three phosphatidylcholines. Although PFOA's effect on T_m and the transition width decreased in the order DMPC > DPPC > DSPC, its relative effect on the phase behavior was largely independent of the phosphatidylcholine. PFOA caused swelling of DMPC but not DPPC …

Shorebird Migration Ecology At Monomoy National Wildlife Refuge, Stephanie Lianne Koch

Open Access Dissertations

Many species of shorebirds (Charadrii) are long-distance migrants that rely on disturbance-free stopover sites with abundant food. Adequate protection of stopover sites requires knowledge of migration chronology, effects of anthropogenic disturbances, and factors affecting habitat selection. We studied shorebird migration ecology at Monomoy National Wildlife Refuge (Refuge), Cape Cod, Massachusetts, one of the most important shorebird stopover sites in eastern North America. Our findings can be implemented by land managers in the future to maintain the integrity of this stopover site. In the first manuscript, we studied seasonal variation in shorebird abundance during migration and determined peak periods of human …

Increase In Water Column Denitrification During The Last Deglaciation: The Influence Of Oxygen Demand In The Eastern Equatorial Pacific, P. Martinez, Rebecca S. Robinson

Graduate School of Oceanography Faculty Publications

Here we present organic export production and nitrogen isotope results spanning the last 30 000 years from a core recovered off Costa Rica (Ocean Drilling Program (ODP) Site 1242) on the leading edge of the oxygen minimum zone of the Eastern Tropical North Pacific. Marine export production reveals glacial-interglacial variations with low organic matter (total organic carbon and total nitrogen) contents during warm intervals, twice more during cold episodes and double peaked maximum during the deglaciation, between ~15.5–18.5 and 11–13 ka B.P. When this new export production record is compared with four nearby cores from within the Eastern Pacific along …

Impacts Of Climate Change On Narragansett Bay, Leslie Smith, Sandra Whitehouse, Candace A. Oviatt

Graduate School of Oceanography Faculty Publications

The objective of this paper is to examine the impacts of global climate change on Rhode Island's coastal ecosystems. Average annual air temperature in Rhode Island has increased by 1.7 °C since 1880, water temperatures of Narragansett Bay have increased by 1.2 °C since 1950, precipitation increased 27% between 1895 and 1999, and sea level rose 0.13 m between 1931 and 2007. We can already see the effects of these climatic changes on the Narragansett Bay ecosystem, including ecological changes in the Bay's food web from phytoplankton and Zooplankton to fish, e.g., changes in phenology of seasonal phytoplankton blooms and …

Modeling The Impact Of Declining Sea Ice On The Arctic Marine Planktonic Ecosystem, Jinlun Zhang, Yvette H. Spitz, Michael Steele, Carin Ashjian, Robert Campbell, Léo Berline, Patricia Matrai

Graduate School of Oceanography Faculty Publications

We have developed a coupled 3‐D pan‐Arctic biology/sea ice/ocean model to investigate the impact of declining Arctic sea ice on the marine planktonic ecosystem over 1988–2007. The biophysical model results agree with satellite observations of a generally downward trend in summer sea ice extent during 1988–2007, resulting in an increase in the simulated photosynthetically active radiation (PAR) at the ocean surface and marine primary productivity (PP) in the upper 100 m over open water areas of the Arctic Ocean. The simulated Arctic sea ice thickness has decreased steadily during 1988–2007, leading to an increase in PAR and PP in sea …

Field‐Derived Henry's Law Constants For Polychlorinated Biphenyls In Oceanic Waters, Rosalinda Gioia, Kevin C. Jones, Rainer Lohmann, Luca Nizzetto, Jordi Dachs

Graduate School of Oceanography Faculty Publications

Accurate knowledge of Henry's law constants (K_aw) is very important for fate and transport studies of organic chemicals. Here field‐derived K_aw values for polychlorinated biphenyl (PCB) congeners (PCBs 28, 49, 52, 118, 138, 149, and 153) were determined in the open Atlantic Ocean, at locations where air and seawater were assumed to be at equilibrium. Field‐based K_aw values were derived from air and seawater samples simultaneously collected at these locations, and their relationship with temperature was determined. The average field‐derived K_aw for PCBs 28, 49, 52, 118, and 138 was generally 2–3 times higher …

Uri Undergraduate And Graduate Course Catalog 2010-2011, University Of Rhode Island

URI Course Catalogs Archive

This is a digitized, downloadable version of the University of Rhode Island course catalog.

Study Of Stability Of Time-Domain Features For Electromyographic Pattern Recognition, Dennis Tkach, He Huang, Todd A. Kuiken

Electrical, Computer, and Biomedical Engineering Faculty Publications

Background: Significant progress has been made towards the clinical application of human-machine interfaces (HMIs) based on electromyographic (EMG) pattern recognition for various rehabilitation purposes. Making this technology practical and available to patients with motor deficits requires overcoming real-world challenges, such as physical and physiological changes, that result in variations in EMG signals and systems that are unreliable for long-term use. In this study, we aimed to address these challenges by (1) investigating the stability of time-domain EMG features during changes in the EMG signals and (2) identifying the feature sets that would provide the most robust EMG pattern recognition.

Methods: …

The Effects Of Concentric Ring Electrode Electrical Stimulation On Rat Skin, Walter Besio, V. Sharma, J. Spaulding

Electrical, Computer, and Biomedical Engineering Faculty Publications

Surface electrodes are commonly used electrodes clinically, in applications such as functional electrical stimulation for the restoration of motor functions, pain relief, transcutaneous electrical nerve stimulation, electrocardiographic monitoring, defibrillation, surface cardiac pacing, and advanced drug delivery systems. Common to these applications are occasional reports of pain, tissue damage, rash, or burns on the skin at the point where electrodes are placed. In this study, we quantitatively analyzed the effects of acute noninvasive electrical stimulation from concentric ring electrodes (CRE) to determine the maximum safe current limit. We developed a three-dimensional multi-layer model and calculated the temperature profile under the CRE …

Seasonal Movement Of The American Horseshoe Crab Limulus Polyphemus In A Semi-Enclosed Bay On Cape Cod, Massachusetts (Usa) As Determined By Acoustic Telemetry, Mary-Jane James-Pirri

Graduate School of Oceanography Faculty Publications

American horseshoe crabs Limulus polyphemus were tracked using acoustic telemetry and traditional tagging in a semi-enclosed bay on Cape Cod (Pleasant Bay), Massachusetts, USA, to determine seasonal movement patterns. Fifty-five actively spawning females were fitted with transmitters in 2008 and 2009 and were tracked using acoustic telemetry from May 2008 through July 2010. Fifteen crabs with transmitters also had archive depth-temperature tags attached. In addition, over 2000 spawning crabs (males and females) were tagged with US Fish and Wildlife (USFWS) button tags over the same period. Ninety-one percent of the crabs with transmitters were detected during this study. In the …

Biology And Ecology Of European Natural Enemies Of Swallow-Worts (Vincetoxicum) And The Potential For Biological Control, Aaron Scott Weed

Open Access Dissertations

A biological control program was initiated against two European swallow-worts in North America to minimize their negative effects on native flora and fauna. In manuscript one, populations of Vincetoxicum spp. were surveyed for insect herbivores across Europe to locate new biological control agents and examine herbivore-plant associations. In laboratory studies, larval performance of all herbivores was generally better on the target weeds than V. hirundinaria and are promising as biological control agents. In manuscript two, the preliminary host specificity of H. opulenta was evaluated in quarantine against 34 species. Larvae only completed development on Vincetoxicum although partial larval development occurred …