Life Sciences Commons^™

Ipla2Β Overexpression In Smooth Muscle Exacerbates Angiotensin Ii-Induced Hypertension And Vascular Remodeling, Lindsay E Calderon, Shu Liu, Wen Su, Zhongwen Xie, Zhenheng Guo, Wanda Eberhard, Ming C. Gong

Physiology Faculty Publications

OBJECTIVES: Calcium independent group VIA phospholipase A₂ (iPLA₂β) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA₂β affects vascular morphology and blood pressure is unknown. The current study addresses this question by evaluating the basal- and angiotensin II infusion-induced vascular remodeling and hypertension in smooth muscle specific iPLA₂β transgenic (iPLA₂β-Tg) mice.

METHOD AND RESULTS: Blood pressure was monitored by radiotelemetry and vascular remodeling was assessed by morphologic analysis. We found that the angiotensin II-induced increase in diastolic pressure was significantly higher in iPLA₂β-Tg …

Role Of Sec61alpha In The Regulated Transfer Of The Ribosome-Nascent Chain Complex From The Signal Recognition Particle To The Translocation Channel, Weiqun Song, David Raden, Elisabet Mandon, Reid Gilmore

Elisabet Mandon

Targeting of ribosome-nascent chain complexes to the translocon in the endoplasmic reticulum is mediated by the concerted action of the signal recognition particle (SRP) and the SRP receptor (SR). Ribosome-stripped microsomes were digested with proteases to sever cytoplasmic domains of SRalpha, SRbeta, TRAM, and the Sec61 complex. We characterized protein translocation intermediates that accumulate when Sec61alpha or SRbeta is inactivated by proteolysis. In the absence of a functional Sec61 complex, dissociation of SRP54 from the signal sequence is blocked. Experiments using SR proteoliposomes confirmed the assembly of a membrane-bound posttargeting intermediate. These results strongly suggest that the Sec61 complex regulates …

A Monomeric Protein In The Golgi Membrane Catalyzes Both N-Deacetylation And N-Sulfation Of Heparan Sulfate, Elisabet Mandon, Ellis Kempner, Masayuki Ishihara, Carlos Hirschberg

Elisabet Mandon

Recent studies have shown that the rat liver heparan sulfate N-deacetylase/N-sulfotransferase is a glycoprotein encoded by a single polypeptide chain of 882 amino acids. Using radiation inactivation analyses, we have now determined that in rat liver Golgi vesicles the target size for the N-deacetylase is 88 +/- 14 kDa, whereas that of the N-sulfotransferase is 92 +/- 8 kDa. These results, together with previous biochemical and molecular cloning approaches, demonstrate that 1) in rat liver Golgi membranes there exists only on population of molecules expressing both activities, 2) the active protein in the Golgi membrane functions as a monomer, and …

Dual Recognition Of The Ribosome And The Signal Recognition Particle By The Srp Receptor During Protein Targeting To The Endoplasmic Reticulum, Elisabet C. Mandon, Ying Jiang, Reid Gilmore

Elisabet Mandon

We have analyzed the interactions between the signal recognition particle (SRP), the SRP receptor (SR), and the ribosome using GTPase assays, biosensor experiments, and ribosome binding assays. Possible mechanisms that could contribute to an enhanced affinity between the SR and the SRP-ribosome nascent chain complex to promote protein translocation under physiological ionic strength conditions have been explored. Ribosomes or 60S large ribosomal subunits activate the GTPase cycle of SRP54 and SRalpha by providing a platform for assembly of the SRP-SR complex. Biosensor experiments revealed high-affinity, saturable binding of ribosomes or large ribosomal subunits to the SR. Remarkably, the SR has …

Identification Of Cytoplasmic Residues Of Sec61p Involved In Ribosome Binding And Cotranslational Translocation, Zhiliang Cheng, Ying Jiang, Elisabet Mandon, Reid Gilmore

Elisabet Mandon

The cytoplasmic surface of Sec61p is the binding site for the ribosome and has been proposed to interact with the signal recognition particle receptor during targeting of the ribosome nascent chain complex to the translocation channel. Point mutations in cytoplasmic loops six (L6) and eight (L8) of yeast Sec61p cause reductions in growth rates and defects in the translocation of nascent polypeptides that use the cotranslational translocation pathway. Sec61 heterotrimers isolated from the L8 sec61 mutants have a greatly reduced affinity for 80S ribosomes. Cytoplasmic accumulation of protein precursors demonstrates that the initial contact between the large ribosomal subunit and …

Purification Of The Golgi Adenosine 3'-Phosphate 5'-Phosphosulfate Transporter, A Homodimer Within The Membrane, Elisabet Mandon, Marcos Milla, Ellis Kempner, Carlos Hirschberg

Elisabet Mandon

Sulfation of proteoglycans, secretory and membrane proteins, and glycolipids occurs in the lumen of the Golgi apparatus. Adenosine 3'-phosphate 5'-phosphosulfate (PAPS), the sulfate donor in these reactions, must be transported from the cytosol, its site of synthesis, into the lumen of the Golgi apparatus. We have identified and purified to apparent homogeneity the rat liver Golgi membrane PAPS transporter by a combination of conventional and affinity chromatography as well as photoaffinity radiolabeling with adenosine 3',5'-bisphosphate, a competitive inhibitor of PAPS transport. The transporter, a 75-kDa protein, was purified 70,000-fold over homogenate (6% yield) and transported PAPS into phosphatidylcholine liposomes selectively …

Environmentally Realistic Exposure To The Herbicide Atrazine Alters Some Sexually Selected Traits In Male Guppies, Kausalya Shenoy

Biology Faculty Publications

Male mating signals, including ornaments and courtship displays, and other sexually selected traits, like male-male aggression, are largely controlled by sex hormones. Environmental pollutants, notably endocrine disrupting compounds, can interfere with the proper functioning of hormones, thereby impacting the expression of hormonally regulated traits. Atrazine, one of the most widely used herbicides, can alter sex hormone levels in exposed animals. I tested the effects of environmentally relevant atrazine exposures on mating signals and behaviors in male guppies, a sexually dimorphic freshwater fish. Prolonged atrazine exposure reduced the expression of two honest signals: the area of orange spots (ornaments) and the …

Usp8 Promotes Smoothened Signaling By Preventing Its Ubiquitination And Changing Its Subcellular Localization, Ruohan Xia, Hongge Jia, Junkai Fan, Yajuan Liu, Jianhang Jia

Molecular and Cellular Biochemistry Faculty Publications

The seven transmembrane protein Smoothened (Smo) is a critical component of the Hedgehog (Hh) signaling pathway and is regulated by phosphorylation, dimerization, and cell-surface accumulation upon Hh stimulation. However, it is not clear how Hh regulates Smo accumulation on the cell surface or how Hh regulates the intracellular trafficking of Smo. In addition, little is known about whether ubiquitination is involved in Smo regulation. In this study, we demonstrate that Smo is multi-monoubiquitinated and that Smo ubiquitination is inhibited by Hh and by phosphorylation. Using an in vivo RNAi screen, we identified ubiquitin-specific protease 8 (USP8) as a deubiquitinase that …

Hiv-1 Tat Triggers Nuclear Localization Of Zo-1 Via Rho Signaling And Camp Response Element-Binding Protein Activation, Yu Zhong, Bei Zhang, Sung Yong Eum, Michal Toborek

Neurosurgery Faculty Publications

The human immunodeficiency virus (HIV)-specific protein trans-activator of transcription (Tat) can contribute to the dysfunction of brain endothelial cells and HIV trafficking into the brain by disrupting tight junction (TJ) integrity at the blood–brain barrier (BBB) level. Specific TJ proteins, such as zonula occludens (ZO) proteins, localize not only at the cell–cell borders but are also present in the nuclei. The objective of the present study was to evaluate the mechanisms and significance of Tat-induced nuclear localization of ZO-1. Treatment of a brain endothelial cell line (hCMEC/D3 cells) with Tat resulted in a decrease in total levels of ZO-1 but …

The Complete Mitochondrial Genome And Novel Gene Arrangement Of The Unique-Headed Bug Stenopirates Sp. (Hemiptera: Enicocephalidae), Hu Li, Hui Liu, Aimin Shi, Pavel Stys, Xuguo Zhou, Wanzhi Cai

Entomology Faculty Publications

Many of true bugs are important insect pests to cultivated crops and some are important vectors of human diseases, but few cladistic analyses have addressed relationships among the seven infraorders of Heteroptera. The Enicocephalomorpha and Nepomorpha are consider the basal groups of Heteroptera, but the basal-most lineage remains unresolved. Here we report the mitochondrial genome of the unique-headed bug Stenopirates sp., the first mitochondrial genome sequenced from Enicocephalomorpha. The Stenopirates sp. mitochondrial genome is a typical circular DNA molecule of 15, 384 bp in length, and contains 37 genes and a large non-coding fragment. The gene order differs substantially from …

Mapping Migratory Bird Prevalence Using Remote Sensing Data Fusion, Anu Swatantran, Ralph Dubayah, Scott Goetz, Michelle Hofton, Matthew G. Betts, Mindy Sun, Marc Simard, Richard Holmes

Dartmouth Scholarship

Background: Improved maps of species distributions are important for effective management of wildlife under increasing anthropogenic pressures. Recent advances in lidar and radar remote sensing have shown considerable potential for mapping forest structure and habitat characteristics across landscapes. However, their relative efficacies and integrated use in habitat mapping remain largely unexplored. We evaluated the use of lidar, radar and multispectral remote sensing data in predicting multi-year bird detections or prevalence for 8 migratory songbird species in the unfragmented temperate deciduous forests of New Hampshire, USA.

Methodology and Principal Findings: A set of 104 predictor variables describing vegetation vertical structure and …

Pegylated Arginine Deiminase Downregulates Colitis In Murine Models, Helieh S. Oz, Jian Zhong, Willem J. S. De Villiers

Physiology Faculty Publications

Arginine deiminase (ADI), an arginine-metabolizing enzyme involved in cell signaling, is dysregulated in multiple inflammatory diseases and cancers. We hypothesized that pegylated ADI (ADI-PEG) provide protection against colitis.

METHODS: Dextran sodium sulfate colitis was induced in IL-10-deficient and BALB/c (WT) mice. ADI-PEG was administered i.p., and inflammatory mediators and pathology were evaluated.

RESULTS: Acute colitis in mice was manifested by increases in inflammatory biomarkers, such as serum amyloid A (SAA, P < 0.001), IL-12 p40, and disease index (3-Fold). In contrast, ADI-PEG significantly decreased clinical disease index, SAA levels, and inflammatory cytokines in blood as well as in colonic explants. Animals developed moderate (2.2 ± 0.3 WT) to severe (3.6 ± 0.5 IL-10 deficient) colonic pathology; and ADI-PEG treatment significantly improved the severity of colitis (P < 0.05). Marked infiltration of CD68+ macrophages and iNOS expression were detected in colonic submucosa in colitic animals but not detected in ADI-PEG-treated animals.

CONCLUSION: ADI-PEG attenuated inflammatory responses by suppression of macrophage infiltration and iNOS expression in colitic animals. ADI-PEG can serve as a potential therapeutic value in IBD.

Creation Of A Natural History Information Database With Mobile Device Access For The Pace Campus In Pleasantville, Joshua J. Schwartz, Martina Blackwood

Cornerstone 3 Reports : Interdisciplinary Informatics

No abstract provided.

Testing Phylogenetic Hypotheses Of The Subgenera Of The Freshwater Crayfish Genus Cambarus (Decapoda: Cambaridae)., Jesse W Breinholt, Megan L Porter, Keith A Crandall

Computational Biology Institute

BACKGROUND: The genus Cambarus is one of three most species rich crayfish genera in the Northern Hemisphere. The genus has its center of diversity in the Southern Appalachians of the United States and has been divided into 12 subgenera. Using Cambarus we test the correspondence of subgeneric designations based on morphology used in traditional crayfish taxonomy to the underlying evolutionary history for these crayfish. We further test for significant correlation and explanatory power of geographic distance, taxonomic model, and a habitat model to estimated phylogenetic distance with multiple variable regression.

METHODOLOGY/PRINCIPAL FINDINGS: We use three mitochondrial and one nuclear gene …

Nutrition, Inflammation, And Infectious Disease, Helieh S. Oz, Sung-Ling Yeh

Physiology Faculty Publications

No abstract provided.

Methamphetamine Administration Targets Multiple Immune Subsets And Induces Phenotypic Alterations Suggestive Of Immunosuppression., Robert Z. Harms, Brenda M. Morsey, Craig W. Boyer, Howard S. Fox, Nora E. Sarvetnick

Journal Articles: Regenerative Medicine

Methamphetamine (Meth) is a widely abused stimulant and its users are at increased risk for multiple infectious diseases. To determine the impact of meth on the immune system, we utilized a murine model that simulates the process of meth consumption in a typical addict. Our phenotypic analysis of leukocytes from this dose escalation model revealed that meth affected key immune subsets. Meth administration led to a decrease in abundance of natural killer (NK) cells and the remaining NK cells possessed a phenotype suggesting reduced responsiveness. Dendritic cells (DCs) and Gr-1(high) monocytes/macrophages were also decreased in abundance while Gr-1(low) monocytes/macrophages appear …

Gene Expression Profiling In The Thiamethoxam Resistant And Susceptible B-Biotype Sweetpotato Whitefly, Bemisia Tabaci, Wen Xie, Xin Yang, Shao-Ii Wang, Qing-Jun Wu, Ni-Na Yang, Ru-Mei Li, Xiao-Guo Jiao, Hui-Peng Pan, Bai-Ming Liu, Yun-Tao Feng, Bao-Yun Xu, Xuguo Zhou, You-Jun Zhang

Entomology Faculty Publications

Thiamethoxam has been used as a major insecticide to control the B-biotype sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Due to its excessive use, a high level of resistance to thiamethoxam has developed worldwide over the past several years. To better understand the molecular mechanisms underlying this resistance in B. tabaci, gene profiles between the thiamethoxam-resistant and thiamethoxam-susceptible strains were investigated using the suppression subtractive hybridization (SSH) library approach. A total of 72 and 52 upand down-regulated genes were obtained from the forward and reverse SSH libraries, respectively. These expressed sequence tags (ESTs) belong to several functional categories based …

Minimum Cost Of Transport In Asian Elephants: Do We Really Need A Bigger Elephant?, V. A. Langman, M. F. Rowe, T. J. Roberts, N. V. Langman, C. R. Taylor

Dartmouth Scholarship

Body mass is the primary determinant of an animal’s energy requirements. At their optimum walking speed, large animals have lower mass-specific energy requirements for locomotion than small ones. In animals ranging in size from 0.8 g (roach) to 260 kg (zebu steer), the minimum cost of transport (COT_min) decreases with increasing body size roughly as COT_min∝body mass (M_b)^{–0.316±0.023} (95% CI). Typically, the variation of COT_min with body mass is weaker at the intraspecific level as a result of physiological and geometric similarity within closely related species. The interspecific relationship estimates that …

Genetic Control Of A Central Pattern Generator: Rhythmic Oromotor Movement In Mice Is Controlled By A Major Locus Near Atp1a2, Steven J. St. John, John D. Boughter Jr, Megan K. Mulligan, Kenichi Tokita, Lu Lu, Detlef H. Heck, Robert W. Williams

Faculty Publications

calreticulin, Animals, Chromosome Mapping, Mammalian Chromosomes, Gene Expression Regulation, Genetic Linkage, Genome-Wide Association Study. Inbred C57BL Mice, Inbred DBA Mice, Quantitative Trait Loci, Sodium-Potassium-Exchanging ATPase/genetics, Atp1a2 protein, Sodium-Potassium-Exchanging ATPase, feeding behavior, drinking behavior, mice, central pattern generator, genetic control

Optimal Body Size With Respect To Maximal Speed For The Yellow-Spotted Monitor Lizard (Varanus Panoptes; Varanidae), Christofer J. Clemente, Philip C. Withers, Graham Thompson

Research outputs 2012

Studies of locomotor performance often link variation in morphology with ecology. While maximum sprint speed is a commonly used performance variable, the absolute limits for this performance trait are not completely understood. Absolute maximal speed has often been shown to increase linearly with body size, but several comparative studies covering a large range of body sizes suggest that maximal speed does not increase indefinitely with body mass but rather reaches an optimum after which speed declines. Because of the comparative nature of these studies, it is difficult to determine whether this decrease is due to biomechanical constraints on maximal speed …

Fussy Feeders: Phyllosoma Larvae Of The Western Rocklobster (Panulirus Cygnus) Demonstrate Prey Preference, M I Saunders, P A Thompson, A G Jeffs, Christin Sawstrom, N Sachlikidis, L E Beckley, A M Waite

Research outputs 2012

The Western Rocklobster (Panulirus cygnus) is the most valuable single species fishery in Australia and the largest single country spiny lobster fishery in the world. In recent years a well-known relationship between oceanographic conditions and lobster recruitment has become uncoupled, with significantly lower recruitment than expected, generating interest in the factors influencing survival and development of the planktonic larval stages. The nutritional requirements and wild prey of the planktotrophic larval stage (phyllosoma) of P. cygnus were previously unknown, hampering both management and aquaculture efforts for this species. Ship-board feeding trials of wild-caught mid-late stage P. cygnus phyllosoma in the eastern …

Dimerization And Heme Binding Are Conserved In Amphibian And Starfish Homologues Of The Microrna Processing Protein Dgcr8., Rachel Senturia, Arthur Laganowsky, Ian Barr, Brooke D. Scheidemantle, Feng Guo

Natural Sciences and Mathematics | Faculty Scholarship

Human DiGeorge Critical Region 8 (DGCR8) is an essential microRNA (miRNA) processing factor that is activated via direct interaction with Fe(III) heme. In order for DGCR8 to bind heme, it must dimerize using a dimerization domain embedded within its heme-binding domain (HBD). We previously reported a crystal structure of the dimerization domain from human DGCR8, which demonstrated how dimerization results in the formation of a surface important for association with heme. Here, in an attempt to crystallize the HBD, we search for DGCR8 homologues and show that DGCR8 from Patiria miniata (bat star) also binds heme. The extinction coefficients (ε) …