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Found 37769 matches. Displaying 7861-7870
Garbarino J, Pan MH, Chin HF, Lund FW, Maxfield FR, Breslow JL
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STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC
JOURNAL OF LIPID RESEARCH 2012 DEC; 53(12):2716-2725
STARD4, a member of the evolutionarily conserved START gene family, has been implicated in the non-vesicular intracellular transport of cholesterol. However, the direction of transport and the membranes with which this protein interacts are not clear. We present studies of STARD4 function using small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein receptor (LDLR) levels were increased and decreased, respectively. We also observed a decrease in NPC1 protein expression, suggesting the induction of compensatory pathways to maintain cholesterol balance. These data indicate a role for STARD4 in nonvesicular transport of cholesterol from the plasma membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well. -Garbarino, J., M. Pan, H.F. Chin, F.W. Lund, F.R. Maxfield, and J.L. Breslow. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC. J. Lipid Res. 2012. 53: 2716-2725.
Kuroiwa M, Hamada M, Hieda E, Shuto T, Sotogaku N, Flajolet M, Snyder GL, Hendrick JP, Fienberg A, Nishi A
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Muscarinic receptors acting at pre- and post-synaptic sites differentially regulate dopamine/DARPP-32 signaling in striatonigral and striatopallidal neurons
NEUROPHARMACOLOGY 2012 DEC; 63(7):1248-1257
Muscarinic receptors, activated by acetylcholine, play critical roles in the functional regulation of medium spiny neurons in the striatum. However, the muscarinic receptor signaling pathways are not fully elucidated due to their complexity. In this study, we investigated the function of muscarinic receptors in the striatum by monitoring DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of M-r 32 kDa) phosphorylation at Thr34 (the PKA-site) using mouse striatal slices. Treatment of slices with a non-selective muscarinic receptor agonist, oxotremorine (10 mu M), rapidly and transiently increased DARPP-32 phosphorylation. The increase in DARPP-32 phosphorylation was completely abolished either by a dopamine D-1 receptor antagonist (SCH23390), tetrodotoxin, genetic deletion of M5 receptors, muscarinic toxins for M1 and M4 receptors, or 6-hydroxydopamine lesioning of dopaminergic neurons, whereas it was enhanced by nicotine. Analysis in D-1-DARPP-32-Flag/D-2-DARPP-32-Myc transgenic mice revealed that oxotremorine increases DARPP-32 phosphorylation selectively in D-1-type/striatonigral, but not in D-2-type/striatopallidal, neurons. When D-1 and D-2 receptors were blocked by selective antagonists to exclude the effects of released dopamine, oxotremorine increased DARPP-32 Thr34 phosphorylation only in D-2-type/striatopallidal neurons. This increase required activation of M1 receptors and was dependent upon adenosine A(2A) receptor activity. The results demonstrate that muscarinic receptors, especially M5 receptors, act at presynaptic dopaminergic terminals, regulate the release of dopamine in cooperation with nicotinic receptors, and activate D-1 receptor/DARPP-32 signaling in the striatonigral neurons. Muscarinic M1 receptors expressed in striatopallidal neurons interact with adenosine A(2A) receptors and activate DARPP-32 signaling. (C) 2012 Elsevier Ltd. All rights reserved.
Cohen JE, Plank MJ, Law R
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Taylor's law and body size in exploited marine ecosystems
ECOLOGY AND EVOLUTION 2012 DEC; 2(12):3168-3178
Taylor's law (TL), which states that variance in population density is related to mean density via a power law, and density-mass allometry, which states that mean density is related to body mass via a power law, are two of the most widely observed patterns in ecology. Combining these two laws predicts that the variance in density is related to body mass via a power law (variance-mass allometry). Marine size spectra are known to exhibit density-mass allometry, but variance-mass allometry has not been investigated. We show that variance and body mass in unexploited size spectrum models are related by a power law, and that this leads to TL with an exponent slightly <2. These simulated relationships are disrupted less by balanced harvesting, in which fishing effort is spread across a wide range of body sizes, than by size-at-entry fishing, in which only fish above a certain size may legally be caught.
Grant AV, Alter A, Huong NT, Orlova M, Thuc NV, Ba NN, Thai VH, Abel L, Schurr E, Alcais A
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Crohn's Disease Susceptibility Genes are Associated With Leprosy in the Vietnamese Population
JOURNAL OF INFECTIOUS DISEASES 2012 DEC 1; 206(11):1763-1767
A genomewide association study in Chinese patients with leprosy detected association signals in 16 single-nucleotide polymorphisms (SNPs) belonging to 6 loci, of which 4 are related to the NOD2 signaling pathway and are Crohn's disease susceptibility loci. Here, we studied these 16 SNPs as potential leprosy susceptibility factors in 474 Vietnamese leprosy simplex families. We replicated SNPs at HLA-DR-DQ, RIPK2, CCDC122-LACC1, and NOD2 as leprosy susceptibility factors in Vietnam. These results validated the striking overlap in the genetic control of Crohn's disease and leprosy.
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J, Rios AAO, Ryckbosch D, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Walsh S, Yazgan E, Zaganidis N, Basegmez S, Bruno G, Castello R, Ceard L, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Lemaitre V, Liao J, Militaru O, Nuttens C, Pagano D, Pin A, Piotrzkowski K, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Alves GA, Martins MC, Martins T, Pol ME, Souza MHG, Alda WL, Carvalho W, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Malbouisson H, Malek M, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santoro A, Jorge LS, Sznajder A, Pereira AV, Anjos TS, Bernardes CA, Dias FA, Tomei TRFP, Gregores EM, Lagana C, Marinho F, Mercadante PG, Novaes SF, Padula SS, Genchev V, Iaydjiev P, Piperov S, Rodozov M, Stoykova S, Sultanov G, Tcholakov V, Trayanov R, Vutova M, Dimitrov A, Hadjiiska R, Kozhuharov V, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Jiang CH, Liang D, Liang S, Meng X, Tao J, Wang J, Wang X, Wang Z, Xiao H, Xu M, Zang J, 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Ligabue F, Lomtadze T, Martini L, Messineo A, Palla F, Rizzi A, Serban AT, Spagnolo P, Squillacioti P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Barone L, Cavallari F, Del Re D, Diemoz M, Fanelli C, Grassi M, Longo E, Meridiani P, Micheli F, Nourbakhsh S, Organtini G, Paramatti R, Rahatlou S, Soffi L, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Biino C, Cartiglia N, Casasso S, Costa M, Demaria N, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Pastrone N, Pelliccioni M, Potenza A, Romero A, Ruspa M, Sacchi R, Solano A, Staiano A, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Biino C, Cartiglia N, Casasso S, Costa M, Demaria N, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Pastrone N, Pelliccioni M, Potenza A, Romero A, Ruspa M, Sacchi R, Solano A, Staiano A, Belforte S, Candelise V, Casarsa M, Cossutti F, Della Ricca G, Gobbo B, Marone M, Montanino D, Penzo A, Schizzi A, Kim TY, Nam SK, Chang S, Kim DH, Kim GN, Kong DJ, Park H, Son DC, 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Sinthuprasith T, Speer T, Breedon R, Breto G, Sanchez MCD, Chauhan S, Chertok M, Conway J, Conway R, Cox PT, Dolen J, Erbacher R, Gardner M, Houtz R, Ko W, Kopecky A, Lander R, Mall O, Miceli T, Pellett D, Ricci-Tam F, Rutherford B, Searle M, Smith J, Squires M, Tripathi M, Sierra RV, Yohay R, Andreev V, Cline D, Cousins R, Duris J, Erhan S, Everaerts P, Farrell C, Hauser J, Ignatenko M, Jarvis C, Rakness G, Schlein P, Traczyk P, Valuev V, Weber M, Babb J, Clare R, Dinardo ME, Ellison J, Gary JW, Giordano F, Hanson G, Liu H, Long OR, Luthra A, Nguyen H, Paramesvaran S, Sturdy J, Sumowidagdo S, Wilken R, Wimpenny S, Andrews W, Branson JG, Cerati GB, Cittolin S, Evans D, Holzner A, Kelley R, Lebourgeois M, Letts J, Macneill I, Mangano B, Padhi S, Palmer C, Petrucciani G, Pieri M, Sani M, Sharma V, Simon S, Sudano E, Tadel M, Tu Y, Vartak A, Wasserbaech S, Wurthwein F, Yagil A, Yoo J, Barge D, Bellan R, Campagnari C, D'Alfonso M, Danielson T, Flowers K, Geffert P, George C, Golf F, Incandela J, Justus C, Kalavase P, Kovalskyi D, Krutelyov V, Lowette S, Villalba RM, Mccoll N, Pavlunin V, Ribnik J, Richman J, Rossin R, Stuart D, To W, West C, Apresyan A, Bornheim A, Chen Y, Di Marco E, Duarte J, Gataullin M, Ma Y, Mott A, Newman HB, Rogan C, Spiropulu M, Timciuc V, Veverka J, Wilkinson R, Xie S, Yang Y, Zhu RY, Azzolini V, Calamba A, Carroll R, Ferguson T, Iiyama Y, Jang DW, Liu YF, Paulini M, Vogel H, Vorobiev I, Cumalat JP, Drell BR, Ford WT, Gaz A, Lopez EL, Smith JG, Stenson K, Ulmer KA, Wagner SR, Alexander J, Chatterjee A, Eggert N, Gibbons LK, Heltsley B, Hopkins W, Khukhunaishvili A, Kreis B, Mirman N, Kaufman GN, Patterson JR, Ryd A, Salvati E, Sun W, Teo WD, Thom J, Thompson J, Tucker J, Vaughan J, Weng Y, Winstrom L, Wittich P, Winn D, Abdullin S, Albrow M, Anderson J, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Burkett K, Butler JN, Chetluru V, Cheung HWK, Chlebana F, Elvira VD, Fisk I, Freeman J, Gao Y, Green D, Gutsche O, Hanlon J, Harris RM, Hirschauer J, Hooberman B, Jindariani S, Johnson M, Joshi U, Klima B, Kunori S, Kwan S, Leonidopoulos C, Linacre J, Lincoln D, Lipton R, Lykken J, Maeshima K, Marraffino JM, Maruyama S, Mason D, McBride P, Mishra K, Mrenna S, Musienko Y, Newman-Holmes C, O'Dell V, Prokofyev O, Sexton-Kennedy E, Sharma S, Spalding WJ, Spiegel L, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vidal R, Whitmore J, Wu W, Yang F, Yun JC, Acosta D, Avery P, Bourilkov D, Chen M, Cheng T, Das S, De Gruttola M, Di Giovanni GP, Dobur D, Drozdetskiy A, Field RD, Fisher M, Fu Y, Furic IK, Gartner J, Hugon J, Kim B, Konigsberg J, Korytov A, Kropivnitskaya A, Kypreos T, Low JF, Matchev K, Milenovic P, Mitselmakher G, Muniz L, Park M, Remington R, Rinkevicius A, Sellers P, Skhirtladze N, Snowball M, Yelton J, Zakaria M, Gaultney V, Hewamanage S, Lebolo LM, Linn S, Markowitz P, Martinez G, Rodriguez JL, Adams T, Askew A, Bochenek J, Chen J, Diamond B, Gleyzer SV, Haas J, Hagopian S, Hagopian V, Jenkins M, 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Kellogg RG, Kirn M, Kolberg T, Lu Y, Marionneau M, Mignerey AC, Pedro K, Peterman A, Skuja A, Temple J, Tonjes MB, Tonwar SC, Apyan A, Bauer G, Bendavid J, Busza W, Butz E, Cali IA, Chan M, Dutta V, Ceballos GG, Goncharov M, Kim Y, Klute M, Krajczar K, Levin A, Luckey PD, Ma T, Nahn S, Paus C, Ralph D, Roland C, Roland G, Rudolph M, Stephans GSF, Stockli F, Sumorok K, Sung K, Velicanu D, Wenger EA, Wolf R, Wyslouch B, Yang M, Yilmaz Y, Yoon AS, Zanetti M, Zhukova V, Cooper SI, Dahmes B, De Benedetti A, Franzoni G, Gude A, Kao SC, Klapoetke K, Kubota Y, Mans J, Pastika N, Rusack R, Sasseville M, Singovsky A, Tambe N, Turkewitz J, Cremaldi LM, Kroeger R, Perera L, Rahmat R, Sanders DA, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Eads M, Keller J, Kravchenko I, Lazo-Flores J, Malik S, Snow GR, Godshalk A, Iashvili I, Jain S, Kharchilava A, Kumar A, Rappoccio S, Alverson G, Barberis E, Baumgartel D, Chasco M, Haley J, Nash D, Orimoto T, Trocino D, Wood D, Zhang J, Anastassov A, Hahn 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Adair A, Akgun B, Boulahouache C, Ecklund KM, Geurts FJM, Li W, Padley BP, Redjimi R, Roberts J, Zabel J, Betchart B, Bodek A, Chung YS, Covarelli R, de Barbaro P, Demina R, Eshaq Y, Ferbel T, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Miner DC, Vishnevskiy D, Zielinski M, Bhatti A, Ciesielski R, Demortier L, Goulianos K, Lungu G, Malik S, Mesropian C, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Lath A, Panwalkar S, Park M, Patel R, Rekovic V, Robles J, Rose K, Salur S, Schnetzer S, Seitz C, Somalwar S, Stone R, Thomas S, Walker M, Cerizza G, Hollingsworth M, Spanier S, Yang ZC, York A, Eusebi R, Flanagan W, Gilmore J, Kamon T, Khotilovich V, Montalvo R, Osipenkov I, Pakhotin Y, Perloff A, Roe J, Safonov A, Sakuma T, Sengupta S, Suarez I, Tatarinov A, Toback D, Akchurin N, Damgov J, Dragoiu C, Dudero PR, Jeong C, Kovitanggoon K, Lee SW, Libeiro T, Volobouev I, Appelt E, Delannoy AG, Florez C, Greene S, Gurrola A, Johns W, Kurt P, Maguire C, Melo A, Sharma M, Sheldon P, Snook B, Tuo S, Velkovska J, Arenton MW, Balazs M, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Lin C, Neu C, Wood J, Gollapinni S, Harr R, Karchin PE, Don CKK, Lamichhane P, Sakharov A, Anderson M, Belknap D, Borrello L, Carlsmith D, Cepeda M, Dasu S, Friis E, Gray L, Grogg KS, Grothe M, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Klukas J, Lanaro A, Lazaridis C, Loveless R, Mohapatra A, Mozer MU, Ojalvo I, Palmonari F, Pierro GA, Ross I, Savin A, Smith WH, Swanson J
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Search for third-generation leptoquarks and scalar bottom quarks in pp collisions at root s=7 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2012 DEC; ?(12):? Article 055
Results are presented from a search for third-generation leptoquarks and scalar bottom quarks in a sample of proton-proton collisions at root s = 7TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 4.7 fb(-1). A scenario where the new particles are pair produced and each decays to a b quark plus a tau neutrino or neutralino is considered. The number of observed events is found to be in agreement with the standard model prediction. Upper limits are set at 95% confidence level on the production cross sections. Leptoquarks with masses below similar to 450 GeV are excluded. Upper limits in the mass plane of the scalar quark and neutralino are set such that scalar bottom quark masses up to 410 GeV are excluded for neutralino masses of 50 GeV.
Puel A, Cypowyj S, Marodi L, Abel L, Picard C, Casanova JL
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Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis
CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY 2012 DEC; 12(6):616-622
Purpose of review Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent symptomatic infection of the nails, skin and mucosae mostly by Candida albicans. CMC is common in patients with profound primary T-cell immunodeficiency, who often display multiple infectious and autoimmune diseases. Patients with syndromic CMC, including autosomal dominant hyper IgE syndrome (AD-HIES) and autosomal recessive autoimmune polyendocrinopathy syndrome type I (APS-I), display fewer other infections. Patients with isolated CMC (CMCD) rarely display any other severe disease. We review here recent progress in the genetic dissection of these three types of inherited CMC. Recent findings Low IL-17 T-cell proportions were reported in patients with AD-HIES bearing heterozygous STAT3 mutations, prone to CMC and staphylococcal diseases, and in a kindred with autosomal recessive CARD9 deficiency, prone to CMC and other fungal infections. High levels of neutralizing autoantibodies against IL-17 cytokines were documented in patients with APS-I presenting with CMC as their only infectious disease. The first three genetic causes of CMCD were then reported: autosomal recessive IL-17RA and autosomal dominant IL-17F deficiencies and autosomal dominant STAT1 gain-of-function, impairing IL-17-producing T-cell development. Summary Inborn errors of human IL-17 immunity underlie CMC. Impaired IL-17 immunity may therefore account for CMC in other settings, including patients with acquired immunodeficiency.
Modes CD, Warner M, Sanchez-Somolinos C, de Haan LT, Broer D
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Mechanical frustration and spontaneous polygonal folding in active nematic sheets
PHYSICAL REVIEW E 2012 DEC 21; 86(6):? Article 060701
We analyze the bending response to light or heat of a solid nematic disk with a director twisted from being radial on the upper surface to be azimuthal on the lower. We find a number of curl lobes determined purely by the geometry of the mechanical frustration that arises during the response. DOI: 10.1103/PhysRevE.86.060701
Macro L, Jaiswal JK, Simon SM
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Dynamics of clathrin-mediated endocytosis and its requirement for organelle biogenesis in Dictyostelium
JOURNAL OF CELL SCIENCE 2012 DEC 1; 125(23):5721-5732
The protein clathrin mediates one of the major pathways of endocytosis from the extracellular milieu and plasma membrane. In single-cell eukaryotes, such as Saccharomyces cerevisiae, the gene encoding clathrin is not an essential gene, raising the question of whether clathrin conveys specific advantages for multicellularity. Furthermore, in contrast to mammalian cells, endocytosis in S. cerevisiae is not dependent on either clathrin or adaptor protein 2 (AP2), an endocytic adaptor molecule. In this study, we investigated the requirement for components of clathrin-mediated endocytosis (CME) in another unicellular organism, the amoeba Dictyostelium. We identified a heterotetrameric AP2 complex in Dictyostelium that is similar to that which is found in higher eukaryotes. By simultaneously imaging fluorescently tagged clathrin and AP2, we found that, similar to higher eukaryotes, these proteins colocalized to membrane puncta that move into the cell together. In addition, the !
Yessis JL, Kost RG, Lee LM, Coller BS, Henderson DK
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Development of a Research Participants' Perception Survey to Improve Clinical Research
CTS-CLINICAL AND TRANSLATIONAL SCIENCE 2012 DEC; 5(6):452-460
Introduction: Clinical research participants perceptions regarding their experiences during research protocols provide outcome-based insights into the effectiveness of efforts to protect rights and safety, and opportunities to enhance participants clinical research experiences. Use of validated surveys measuring patient-centered outcomes is standard in hospitals, yet no instruments exist to assess outcomes of clinical research processes. Methods: We derived survey questions from data obtained from focus groups comprised of research participants and professionals. We assessed the survey for face/content validity, and privacy/confidentiality protections and fielded it to research participants at 15 centers. We conducted analyses of response rates, sample characteristics, and psychometrics, including survey and item completion and analysis, internal consistency, item internal consistency, criterion-related validity, and item usefulness. Responses were tested for fit into exi!