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https://www.readbyqxmd.com/read/29149325/the-iuphar-bps-guide-to-pharmacology-in-2018-updates-and-expansion-to-encompass-the-new-guide-to-immunopharmacology
#1
Simon D Harding, Joanna L Sharman, Elena Faccenda, Chris Southan, Adam J Pawson, Sam Ireland, Alasdair J G Gray, Liam Bruce, Stephen P H Alexander, Stephen Anderton, Clare Bryant, Anthony P Davenport, Christian Doerig, Doriano Fabbro, Francesca Levi-Schaffer, Michael Spedding, Jamie A Davies
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, www.guidetopharmacology.org) and its precursor IUPHAR-DB, have captured expert-curated interactions between targets and ligands from selected papers in pharmacology and drug discovery since 2003. This resource continues to be developed in conjunction with the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS). As previously described, our unique model of content selection and quality control is based on 96 target-class subcommittees comprising 512 scientists collaborating with in-house curators...
November 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29149197/sieve-analysis-of-breakthrough-hiv-1-sequences-in-hvtn-505-identifies-vaccine-pressure-targeting-the-cd4-binding-site-of-env-gp120
#2
Allan C deCamp, Morgane Rolland, Paul T Edlefsen, Eric Sanders-Buell, Breana Hall, Craig A Magaret, Andrew J Fiore-Gartland, Michal Juraska, Lindsay N Carpp, Shelly T Karuna, Meera Bose, Steven LePore, Shana Miller, Annemarie O'Sullivan, Kultida Poltavee, Hongjun Bai, Kalpana Dommaraju, Hong Zhao, Kim Wong, Lennie Chen, Hasan Ahmed, Derrick Goodman, Matthew Z Tay, Raphael Gottardo, Richard A Koup, Robert Bailer, John R Mascola, Barney S Graham, Mario Roederer, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Elizabeth Adams, Patricia D'Souza, James Kublin, Lawrence Corey, Daniel E Geraghty, Nicole Frahm, Georgia D Tomaras, M Juliana McElrath, Lisa Frenkel, Sheila Styrchak, Sodsai Tovanabutra, Magdalena E Sobieszczyk, Scott M Hammer, Jerome H Kim, James I Mullins, Peter B Gilbert
Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120)...
2017: PloS One
https://www.readbyqxmd.com/read/29148382/high-abundance-and-genetic-variability-of-atypical-porcine-pestivirus-in-pigs-from-europe-and-asia
#3
Alexander Postel, Denise Meyer, Gökce Nur Cagatay, Francesco Feliziani, Gian Mario De Mia, Nicole Fischer, Adam Grundhoff, Vesna Milićević, Ming-Chung Deng, Chia-Yi Chang, Hua-Ji Qiu, Yuan Sun, Michael Wendt, Paul Becher
Atypical porcine pestivirus (APPV) was recently reported to be associated with neurologic disorders in newborn piglets. Investigations of 1,460 serum samples of apparently healthy pigs from different parts of Europe and Asia demonstrate a geographically wide distribution of genetically highly variable APPV and high APPV genome and antibody detection rates.
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29145473/suppression-and-resolution-of-autoimmune-arthritis-by-rhesus-%C3%AE-defensin-1-an-immunomodulatory-macrocyclic-peptide
#4
Justin B Schaal, Dat Q Tran, Akshay Subramanian, Reshma Patel, Teresina Laragione, Kevin D Roberts, Katie Trinh, Prasad Tongaonkar, Patti A Tran, Dmitriy Minond, Gregg B Fields, Paul Beringer, André J Ouellette, Percio S Gulko, Michael E Selsted
θ-defensins constitute a family of macrocyclic peptides expressed exclusively in Old World monkeys. The peptides are pleiotropic effectors of innate immunity, possessing broad spectrum antimicrobial activities and immunoregulatory properties. Here we report that rhesus θ-defensin 1 (RTD-1) is highly effective in arresting and reversing joint disease in a rodent model of rheumatoid arthritis (RA). Parenteral RTD-1 treatment of DA/OlaHsd rats with established pristane-induced arthritis (PIA) rapidly suppressed joint disease progression, restored limb mobility, and preserved normal joint architecture...
2017: PloS One
https://www.readbyqxmd.com/read/29144972/building-bridges-through-science
#5
Thomas Lissek, Michelle Adams, John Adelman, Ehud Ahissar, Mohammed Akaaboune, Huda Akil, Mustafa al'Absi, Fazal Arain, Juan Carlos Arango-Lasprilla, Deniz Atasoy, Jesus Avila, Ashraf Badawi, Hilmar Bading, Abdul Mannan Baig, Jimena Baleriola, Carlos Belmonte, Ilaria Bertocchi, Heinrich Betz, Colin Blakemore, Olaf Blanke, Philipp Boehm-Sturm, Tobias Bonhoeffer, Paolo Bonifazi, Nils Brose, Patrizia Campolongo, Tansu Celikel, Cathy C Chang, Ta-Yuan Chang, Ami Citri, Hollis T Cline, Jesus M Cortes, Kathleen Cullen, Kellie Dean, José M Delgado-Garcia, Mathieu Desroches, John F Disterhoft, John E Dowling, Andreas Draguhn, Sherif F El-Khamisy, Abdeljabbar El Manira, S Ather Enam, Juan M Encinas, Asier Erramuzpe, José A Esteban, Isabel Fariñas, Edmond Fischer, Izumi Fukunaga, Iñigo Gabilondo, Detlev Ganten, Albert Gidon, Juan Carlos Gomez-Esteban, Paul Greengard, Valery Grinevich, Agnés Gruart, Roger Guillemin, Ahmad R Hariri, Bassem Hassan, Michael Häusser, Yasunori Hayashi, Natasha K Hussain, Adnan Abdul Jabbar, Mohamed Jaber, Reinhardt Jahn, Essam Mohammed Janahi, Mohamed Kabbaj, Helmut Kettenmann, Merel Kindt, Shira Knafo, Georg Köhr, Shoji Komai, Harm Krugers, Bernd Kuhn, Nouria Lakhdar Ghazal, Matthew E Larkum, Mickey London, Beat Lutz, Carlos Matute, Luis Martinez-Millan, Mouna Maroun, James McGaugh, Ahmed A Moustafa, Anwar Nasim, Klaus-Armin Nave, Erwin Neher, Karoly Nikolich, Tiago Outeiro, Lucy M Palmer, Olga Penagarikano, Isabel Perez-Otano, Donald W Pfaff, Bruno Poucet, Atta-Ur Rahman, Pedro Ramos-Cabrer, Ali Rashidy-Pour, Richard J Roberts, Serafim Rodrigues, Joshua R Sanes, Andreas T Schaefer, Menahem Segal, Idan Segev, Saad Shafqat, Nikhat Ahmed Siddiqui, Hermona Soreq, Eduardo Soriano-García, Rainer Spanagel, Rolf Sprengel, Greg Stuart, Thomas C Südhof, Jan Tønnesen, Mario Treviño, Basim M Uthman, J Craig Venter, Alexei Verkhratsky, Craig Weiss, Torsten N Wiesel, Emre Yaksi, Ofer Yizhar, Larry J Young, Paul Young, Nasser H Zawia, José L Zugaza, Mazahir T Hasan
Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched "The Science Bridge" initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities.
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29144463/a-single-cell-survey-of-the-small-intestinal-epithelium
#6
Adam L Haber, Moshe Biton, Noga Rogel, Rebecca H Herbst, Karthik Shekhar, Christopher Smillie, Grace Burgin, Toni M Delorey, Michael R Howitt, Yarden Katz, Itay Tirosh, Semir Beyaz, Danielle Dionne, Mei Zhang, Raktima Raychowdhury, Wendy S Garrett, Orit Rozenblatt-Rosen, Hai Ning Shi, Omer Yilmaz, Ramnik J Xavier, Aviv Regev
Intestinal epithelial cells absorb nutrients, respond to microbes, function as a barrier and help to coordinate immune responses. Here we report profiling of 53,193 individual epithelial cells from the small intestine and organoids of mice, which enabled the identification and characterization of previously unknown subtypes of intestinal epithelial cell and their gene signatures. We found unexpected diversity in hormone-secreting enteroendocrine cells and constructed the taxonomy of newly identified subtypes, and distinguished between two subtypes of tuft cell, one of which expresses the epithelial cytokine Tslp and the pan-immune marker CD45, which was not previously associated with non-haematopoietic cells...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144450/corrigendum-high-throughput-discovery-of-novel-developmental-phenotypes
#7
Mary E Dickinson, Ann M Flenniken, Xiao Ji, Lydia Teboul, Michael D Wong, Jacqueline K White, Terrence F Meehan, Wolfgang J Weninger, Henrik Westerberg, Hibret Adissu, Candice N Baker, Lynette Bower, James M Brown, L Brianna Caddle, Francesco Chiani, Dave Clary, James Cleak, Mark J Daly, James M Denegre, Brendan Doe, Mary E Dolan, Sarah M Edie Helmut Fuchs, Valerie Gailus-Durner, Antonella Galli, Alessia Gambadoro, Juan Gallegos, Shiying Guo, Neil R Horner, Chih-Wei Hsu, Sara J Johnson, Sowmya Kalaga, Lance C Keith, Louise Lanoue, Thomas N Lawson, Monkol Lek, Manuel Mark, Susan Marschall, Jeremy Mason, Melissa L McElwee, Susan Newbigging Lauryl M J Nutter, Kevin A Peterson, Ramiro Ramirez-Solis, Douglas J Rowland, Edward Ryder, Kaitlin E Samocha, John R Seavitt, Mohammed Selloum, Zsombor Szoke-Kovacs, Masaru Tamura, Amanda G Trainor, Ilinca Tudose, Shigeharu Wakana, Jonathan Warren, Olivia Wendling, David B West, Leeyean Wong, Atsushi Yoshiki, Wolfgang Wurst, Daniel G MacArthur, Glauco P Tocchini-Valentini, Xiang Gao, Paul Flicek, Allan Bradley, William C Skarnes, Monica J Justice, Helen E Parkinson, Mark Moore, Sara Wells, Robert E Braun, Karen L Svenson, Martin Hrabe de Angelis, Yann Herault, Tim Mohun, Ann-Marie Mallon, R Mark Henkelman, Steve D M Brown, David J Adams, K C Kent Lloyd, Colin McKerlie, Arthur L Beaudet, Maja Bućan Stephen A Murray
This corrects the article DOI: 10.1038/nature19356.
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29142092/response-of-supra-oculomotor-area-neurons-during-combined-saccade-vergence-movements
#8
Adam C Pallus, Mark M G Walton, Michael J Mustari
Combined saccade-vergence movements allow humans and other primates to align their eyes with objects of interest in three-dimensions. In the absence of saccades, vergence movements are typically slow, symmetrical movements of the two eyes in opposite directions. However, combined saccade-vergence movements produce vergence velocities that exceed values observed during vergence alone. This phenomenon is often called "vergence enhancement", or "saccade-facilitated vergence," though it is important to consider that rapid vergence changes, known as "vergence transients," are also observed during conjugate saccades...
November 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29139087/the-role-of-reactive-oxygen-species-in-adipogenic-differentiation
#9
Danielle de Villiers, Marnie Potgieter, Melvin A Ambele, Ladislaus Adam, Chrisna Durandt, Michael S Pepper
Interest in reactive oxygen species and adipocyte differentiation/adipose tissue function is steadily increasing. This is due in part to a search for alternative avenues for combating obesity, which results from the excess accumulation of adipose tissue. Obesity is a major risk factor for complex disorders such as cancer, type 2 diabetes, and cardiovascular diseases. The ability of mesenchymal stromal/stem cells (MSCs) to differentiate into adipocytes is often used as a model for studying adipogenesis in vitro...
November 15, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29138400/accessibility-of-the-histone-h3-tail-in-the-nucleosome-for-binding-of-paired-readers
#10
Jovylyn Gatchalian, Xiaodong Wang, Jinzen Ikebe, Khan L Cox, Adam H Tencer, Yi Zhang, Nathaniel L Burge, Luo Di, Matthew D Gibson, Catherine A Musselman, Michael G Poirier, Hidetoshi Kono, Jeffrey J Hayes, Tatiana G Kutateladze
Combinatorial polyvalent contacts of histone-binding domains or readers commonly mediate localization and activities of chromatin-associated proteins. A pair of readers, the PHD fingers of the protein CHD4, has been shown to bivalently recognize histone H3 tails. Here we describe a mechanism by which these linked but independent readers bind to the intact nucleosome core particle (NCP). Comprehensive NMR, chemical reactivity, molecular dynamics, and fluorescence analyses point to the critical roles of intra-nucleosomal histone-DNA interactions that reduce the accessibility of H3 tails in NCP, the nucleosomal DNA, and the linker between readers in modulating nucleosome- and/or histone-binding activities of the readers...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#11
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136125/effective-connectivity-measured-using-optogenetically-evoked-hemodynamic-signals-exhibits-topography-distinct-from-resting-state-functional-connectivity-in-the-mouse
#12
Adam Q Bauer, Andrew W Kraft, Grant A Baxter, Patrick W Wright, Matthew D Reisman, Annie R Bice, Jasmine J Park, Michael R Bruchas, Abraham Z Snyder, Jin-Moo Lee, Joseph P Culver
Brain connectomics has expanded from histological assessment of axonal projection connectivity (APC) to encompass resting state functional connectivity (RS-FC). RS-FC analyses are efficient for whole-brain mapping, but attempts to explain aspects of RS-FC (e.g., interhemispheric RS-FC) based on APC have been only partially successful. Neuroimaging with hemoglobin alone lacks specificity for determining how activity in a population of cells contributes to RS-FC. Wide-field mapping of optogenetically defined connectivity could provide insights into the brain's structure-function relationship...
November 9, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29134724/biogeography-of-mutualistic-fungi-cultivated-by-leafcutter-ants
#13
Ulrich G Mueller, Heather D Ishak, Sofia M Bruschi, Chad C Smith, Jacob J Herman, Scott E Solomon, Alexander S Mikheyev, Christian Rabeling, Jarrod J Scott, Michael Cooper, Andre Rodrigues, Adriana Ortiz, Carlos Roberto F Brandão, John E Lattke, Fernando C Pagnocca, Stephen A Rehner, Ted R Schultz, Heraldo L Vasconcelos, Rachelle M M Adams, Martin Bollazzi, Rebecca M Clark, Anna G Himler, John S LaPolla, Inara R Leal, Robert A Johnson, Flavio Roces, Jeffrey Sosa-Calvo, Rainer Wirth, Maurício Bacci
Leafcutter ants propagate co-evolving fungi for food. The nearly 50 species of leafcutter ants (Atta, Acromyrmex) range from Argentina to the USA, with the greatest species diversity in southern South America. We elucidate the biogeography of fungi cultivated by leafcutter ants using DNA-sequence and microsatellite-marker analyses of 474 cultivars collected across the leafcutter range. Fungal cultivars belong to two clades (Clade-A, Clade-B). The dominant and widespread Clade-A cultivars form three genotype-clusters, with their relative prevalence corresponding to southern South America, northern South America, and Central & North America...
November 13, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/29133617/response-and-resistance-to-paradox-breaking-braf-inhibitor-in-melanomas-in-vivo-and-ex-vivo
#14
Edward J Hartsough, Curtis H Kugel, Michael J Vido, Adam C Berger, Timothy J Purwin, Allison Goldberg, Michael A Davies, Matthew J Schiewer, Karen E Knudsen, Gideon Bollag, Andrew E Aplin
FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox breaking RAF inhibitor (PLX8394) has been designed. Here we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29133202/glycated-haemoglobin-is-increased-in-critically-ill-patients-with-stress-hyperglycaemia-implications-for-risk-of-diabetes-in-survivors-of-critical-illness
#15
Yang T Du, Palash Kar, Yasmine Ali Abdelhamid, Michael Horowitz, Adam M Deane
It remains uncertain if stress hyperglycaemia (SH) indicates a long-term predisposition to the development of type 2 diabetes. We conducted a retrospective observational study in critically ill patients and found SH to be associated with an increased HbA1c, which may indicate an increased risk of type 2 diabetes.
November 10, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29130427/reduction-of-anxiety-sensitivity-in-relation-to-nicotine-withdrawal-symptoms-during-smoking-cessation-an-examination-among-successful-quitters
#16
Jafar Bakhshaie, Michael J Zvolensky, Kirsten J Langdon, Adam M Leventhal, Norman B Schmidt
Anxiety sensitivity has been implicated as a potential risk factor for post-quit withdrawal symptoms. The present study examined relations between the extent of change in anxiety sensitivity and the course of nicotine withdrawal symptoms experienced during the initial two weeks of a quit attempt among treatment-seeking smokers. The sample consisted of 29 adult daily smokers (34% female; Mage = 47.7, SD = 13.1) who successfully quit and maintained their abstinence. After adjusting for the effects of gender, treatment condition, use of nicotine replacement therapy, nicotine dependence, alcohol use problems, baseline levels of anxiety sensitivity, and reductions in negative affect, greater reductions in anxiety sensitivity were related to faster decreases in withdrawal symptoms...
November 13, 2017: Cognitive Behaviour Therapy
https://www.readbyqxmd.com/read/29129525/multicenter-evaluation-of-the-clinical-utility-of-laparoscopy-assisted-ercp-in-patients-with-roux-en-y-gastric-bypass
#17
Ali M Abbas, Andrew T Strong, David L Diehl, Brian C Brauer, Iris H Lee, Rebecca Burbridge, Jaroslav Zivny, Jennifer T Higa, Marcelo Falcão, Ihab I El Hajj, Paul Tarnasky, Brintha K Enestvedt, Alexander R Ende, Adarsh M Thaker, Rishi Pawa, Priya Jamidar, Kartik Sampath, Eduardo Guimarães Hourneaux de Moura, Richard S Kwon, Alejandro L Suarez, Murad Aburajab, Andrew Y Wang, Mohammad H Shakhatreh, Vivek Kaul, Lorna Kang, Thomas E Kowalski, Rahul Pannala, Jeffrey Tokar, A Aziz Aadam, Demetrios Tzimas, Mihir S Wagh, Peter V Draganov, M D The LA-Ercp Research Group Jeffrey Ponsky, Bruce D Greenwald, Lance T Uradomo, Alyson A McGhan, Shahrad Hakimian, Andrew Ross, Stuart Sherman, Benjamin L Bick, Christopher E Forsmark, Dennis Yang, Anand Gupte, Shailendra Chauhan, Steven J Hughes, Karen Saks, Gennadiy Bakis, Adam W Templeton, Michael Saunders, Alireza Sedarat, John A Evans, Thiruvengadam Muniraj, Timothy B Gardner, Almino C Ramos, Marco Aurelio Santo, Andrew Nett, Gregory A Coté, B Joseph Elmunzer, Kulwinder S Dua, Michael J Nosler, Daniel S Strand, Paul Yeaton, Shivangi Kothari, Asad Ullah, Pushpak Taunk, Patrick Brady, Haim Pinkas, Ashley L Faulx, Haroon Shahid, Jordan Holmes, Davinderbir Pannu, Srinadh Komanduri, Juan Carlos Bucobo, Harry Dhaliwal, Alaa Rostom, Brent W Acker
BACKGROUND AND AIMS: The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases yet standard ERCP is not possible due to surgically altered gastroduodenal anatomy. Laparoscopic-ERCP (LA-ERCP) has been proposed as an option but supporting data are derived from single center small case-series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP...
November 9, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29127604/association-of-adjuvant-therapy-with-improved-survival-in-ampullary-cancer-a-national-cohort-study
#18
Ibrahim Nassour, Linda S Hynan, Alana Christie, Rebecca M Minter, Adam C Yopp, Michael A Choti, John C Mansour, Matthew R Porembka, Sam C Wang
BACKGROUND: There are limited data on the efficacy of adjuvant therapy in ampullary cancer. The aim of this study was to determine whether adjuvant therapy was associated with improved survival for patients with ampullary cancer. METHODS: From the National Cancer Database, we identified ampullary cancer patients who underwent resection between 2004 and 2013. We performed 1:1 propensity score matching, comparing patients who had postoperative observation to patients who received adjuvant chemotherapy (ACT) or adjuvant chemoradiotherapy (ACRT)...
November 10, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/29127155/tumor-suppressor-tsc1-is-a-new-hsp90-co-chaperone-that-facilitates-folding-of-kinase-and-non-kinase-clients
#19
Mark R Woodford, Rebecca A Sager, Elijah Marris, Diana M Dunn, Adam R Blanden, Ryan L Murphy, Nicholas Rensing, Oleg Shapiro, Barry Panaretou, Chrisostomos Prodromou, Stewart N Loh, David H Gutmann, Dimitra Bourboulia, Gennady Bratslavsky, Michael Wong, Mehdi Mollapour
The tumor suppressors Tsc1 and Tsc2 form the tuberous sclerosis complex (TSC), a regulator of mTOR activity. Tsc1 stabilizes Tsc2; however, the precise mechanism involved remains elusive. The molecular chaperone heat-shock protein 90 (Hsp90) is an essential component of the cellular homeostatic machinery in eukaryotes. Here, we show that Tsc1 is a new co-chaperone for Hsp90 that inhibits its ATPase activity. The C-terminal domain of Tsc1 (998-1,164 aa) forms a homodimer and binds to both protomers of the Hsp90 middle domain...
November 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29127147/igg1-is-required-for-optimal-protection-after-immunization-with-the-purified-porin-ompd-from-salmonella-typhimurium
#20
Yang Zhang, Coral Dominguez-Medina, Nicola J Cumley, Jennifer N Heath, Sarah J Essex, Saeeda Bobat, Anna Schager, Margaret Goodall, Sven Kracker, Christopher D Buckley, Robin C May, Robert A Kingsley, Calman A MacLennan, Constantino López-Macías, Adam F Cunningham, Kai-Michael Toellner
In mice, the IgG subclass induced after Ag encounter can reflect the nature of the Ag. Th2 Ags such as alum-precipitated proteins and helminths induce IgG1, whereas Th1 Ags, such as Salmonella Typhimurium, predominantly induce IgG2a. The contribution of different IgG isotypes to protection against bacteria such as S. Typhimurium is unclear, although as IgG2a is induced by natural infection, it is assumed this isotype is important. Previously, we have shown that purified S. Typhimurium porins including outer membrane protein OmpD, which induce both IgG1 and IgG2a in mice, provide protection to S...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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