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Ulf klein

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https://www.readbyqxmd.com/read/29649236/predictive-value-for-cardiovascular-events-of-common-carotid-intima-media-thickness-and-its-rate-of-change-in-individuals-at-high-cardiovascular-risk-results-from-the-prog-imt-collaboration
#1
Matthias W Lorenz, Lu Gao, Kathrin Ziegelbauer, Giuseppe Danilo Norata, Jean Philippe Empana, Irene Schmidtmann, Hung-Ju Lin, Stela McLachlan, Lena Bokemark, Kimmo Ronkainen, Mauro Amato, Ulf Schminke, Sathanur R Srinivasan, Lars Lind, Shuhei Okazaki, Coen D A Stehouwer, Peter Willeit, Joseph F Polak, Helmuth Steinmetz, Dirk Sander, Holger Poppert, Moise Desvarieux, M Arfan Ikram, Stein Harald Johnsen, Daniel Staub, Cesare R Sirtori, Bernhard Iglseder, Oscar Beloqui, Gunnar Engström, Alfonso Friera, Francesco Rozza, Wuxiang Xie, Grace Parraga, Liliana Grigore, Matthieu Plichart, Stefan Blankenberg, Ta-Chen Su, Caroline Schmidt, Tomi-Pekka Tuomainen, Fabrizio Veglia, Henry Völzke, Giel Nijpels, Johann Willeit, Ralph L Sacco, Oscar H Franco, Heiko Uthoff, Bo Hedblad, Carmen Suarez, Raffaele Izzo, Dong Zhao, Thapat Wannarong, Alberico Catapano, Pierre Ducimetiere, Christine Espinola-Klein, Kuo-Liong Chien, Jackie F Price, Göran Bergström, Jussi Kauhanen, Elena Tremoli, Marcus Dörr, Gerald Berenson, Kazuo Kitagawa, Jacqueline M Dekker, Stefan Kiechl, Matthias Sitzer, Horst Bickel, Tatjana Rundek, Albert Hofman, Ellisiv B Mathiesen, Samuela Castelnuovo, Manuel F Landecho, Maria Rosvall, Rafael Gabriel, Nicola de Luca, Jing Liu, Damiano Baldassarre, Maryam Kavousi, Eric de Groot, Michiel L Bots, David N Yanez, Simon G Thompson
AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events...
2018: PloS One
https://www.readbyqxmd.com/read/29562201/cbl-ubiquitin-ligases-control-b-cell-exit-from-the-germinal-center-reaction
#2
Xin Li, Adeline Gadzinsky, Liying Gong, Haijun Tong, Virginie Calderon, Yue Li, Daisuke Kitamura, Ulf Klein, Wallace Y Langdon, Fajian Hou, Yong-Rui Zou, Hua Gu
Selective expansion of high-affinity antigen-specific B cells in germinal centers (GCs) is a key event in antibody affinity maturation. GC B cells with improved affinity can either continue affinity-driven selection or exit the GC to differentiate into plasma cells (PCs) or memory B cells. Here we found that deleting E3 ubiquitin ligases Cbl and Cbl-b (Cbls) in GC B cells resulted in the early exit of high-affinity antigen-specific B cells from the GC reaction and thus impaired clonal expansion. Cbls were highly expressed in GC light zone (LZ) B cells, where they promoted the ubiquitination and degradation of Irf4, a transcription factor facilitating PC fate choice...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29459403/the-alternative-nf-%C3%AE%C2%BAb-pathway-in-regulatory-t-cell-homeostasis-and-suppressive-function
#3
Yenkel Grinberg-Bleyer, Rachel Caron, John J Seeley, Nilushi S De Silva, Christian W Schindler, Matthew S Hayden, Ulf Klein, Sankar Ghosh
CD4+ Foxp3+ regulatory T cells (Tregs) are essential regulators of immune responses. Perturbation of Treg homeostasis or function can lead to uncontrolled inflammation and autoimmunity. Therefore, understanding the molecular mechanisms involved in Treg biology remains an active area of investigation. It has been shown previously that the NF-κB family of transcription factors, in particular, the canonical pathway subunits, c-Rel and p65, are crucial for the development, maintenance, and function of Tregs. However, the role of the alternative NF-κB pathway components, p100 and RelB, in Treg biology remains unclear...
April 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28944344/irf4-couples-anabolic-metabolism-to-th1-cell-fate-determination
#4
Radomir Kratchmarov, Simone A Nish, Wen-Hsuan W Lin, William C Adams, Yen-Hua Chen, Bonnie Yen, Nyanza J Rothman, Ulf Klein, Steven L Reiner
Anabolic metabolism in lymphocytes promotes plasmablast and cytotoxic T cell differentiation at the expense of self-renewal. Heightened expression and function of the transcription factor IFN regulatory factor 4 (IRF4) accompany enhanced anabolic induction and full commitment to functional differentiation in B cells and CD8(+) T cells. In this study, we used a genetic approach to determine whether IRF4 plays an analogous role in Th1 cell induction. Our findings indicate that IRF4 promotes determined Th1 cell differentiation in tandem with anabolic metabolism of CD4(+) T cells...
September 1, 2017: ImmunoHorizons
https://www.readbyqxmd.com/read/28923481/adam17-is-the-main-sheddase-for-the-generation-of-human-triggering-receptor-expressed-in-myeloid-cells-htrem2-ectodomain-and-cleaves-trem2-after-histidine-157
#5
Dominik Feuerbach, Patrick Schindler, Carmen Barske, Stefanie Joller, Edwige Beng-Louka, Katie A Worringer, Sravya Kommineni, Ajamete Kaykas, Daniel J Ho, Chaoyang Ye, Karl Welzenbach, Gaelle Elain, Laurent Klein, Irena Brzak, Anis K Mir, Christopher J Farady, Reiner Aichholz, Simone Popp, Nathalie George, Ulf Neumann
Triggering receptor expressed in myeloid cells (TREM2) is a member of the immunoglobulin superfamily and is expressed in macrophages, dendritic cells, microglia, and osteoclasts. TREM2 plays a role in phagocytosis, regulates release of cytokine, contributes to microglia maintenance, and its ectodomain is shed from the cell surface. Here, the question was addressed at which position sheddases cleave TREM2 and what are the proteases involved in this process. Using both pharmacological and genetic approaches we report that the main protease contributing to the release of TREM2 ectodomain is ADAM17, (a disintegrin and metalloproteinase domain containing protein, also called TACE, TNFα converting enzyme) while ADAM10 plays a minor role...
November 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28889947/an-nf-%C3%AE%C2%BAb-transcription-factor-dependent-lineage-specific-transcriptional-program-promotes-regulatory-t-cell-identity-and-function
#6
Hyunju Oh, Yenkel Grinberg-Bleyer, Will Liao, Dillon Maloney, Pingzhang Wang, Zikai Wu, Jiguang Wang, Dev M Bhatt, Nicole Heise, Roland M Schmid, Matthew S Hayden, Ulf Klein, Raul Rabadan, Sankar Ghosh
Both conventional T (Tconv) cells and regulatory T (Treg) cells are activated through ligation of the T cell receptor (TCR) complex, leading to the induction of the transcription factor NF-κB. In Tconv cells, NF-κB regulates expression of genes essential for T cell activation, proliferation, and function. However the role of NF-κB in Treg function remains unclear. We conditionally deleted canonical NF-κB members p65 and c-Rel in developing and mature Treg cells and found they have unique but partially redundant roles...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28886380/nf-%C3%AE%C2%BAb-c-rel-is-crucial-for-the-regulatory-t-cell-immune-checkpoint-in-cancer
#7
Yenkel Grinberg-Bleyer, Hyunju Oh, Alexis Desrichard, Dev M Bhatt, Rachel Caron, Timothy A Chan, Roland M Schmid, Ulf Klein, Matthew S Hayden, Sankar Ghosh
Regulatory T cells (Tregs) play a pivotal role in the inhibition of anti-tumor immune responses. Understanding the mechanisms governing Treg homeostasis may therefore be important for development of effective tumor immunotherapy. We have recently demonstrated a key role for the canonical nuclear factor κB (NF-κB) subunits, p65 and c-Rel, in Treg identity and function. In this report, we show that NF-κB c-Rel ablation specifically impairs the generation and maintenance of the activated Treg (aTreg) subset, which is known to be enriched at sites of tumors...
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28832619/correction-genome-wide-physical-activity-interactions-in-adiposity-a-meta-analysis-of-200-452-adults
#8
Mariaelisa Graff, Robert A Scott, Anne E Justice, Kristin L Young, Mary F Feitosa, Llilda Barata, Thomas W Winkler, Audrey Y Chu, Anubha Mahajan, David Hadley, Luting Xue, Tsegaselassie Workalemahu, Nancy L Heard-Costa, Marcel den Hoed, Tarunveer S Ahluwalia, Qibin Qi, Julius S Ngwa, Frida Renström, Lydia Quaye, John D Eicher, James E Hayes, Marilyn Cornelis, Zoltan Kutalik, Elise Lim, Jian'an Luan, Jennifer E Huffman, Weihua Zhang, Wei Zhao, Paula J Griffin, Toomas Haller, Shafqat Ahmad, Pedro M Marques-Vidal, Stephanie Bien, Loic Yengo, Alexander Teumer, Albert Vernon Smith, Meena Kumari, Marie Neergaard Harder, Johanne Marie Justesen, Marcus E Kleber, Mette Hollensted, Kurt Lohman, Natalia V Rivera, John B Whitfield, Jing Hua Zhao, Heather M Stringham, Leo-Pekka Lyytikäinen, Charlotte Huppertz, Gonneke Willemsen, Wouter J Peyrot, Ying Wu, Kati Kristiansson, Ayse Demirkan, Myriam Fornage, Maija Hassinen, Lawrence F Bielak, Gemma Cadby, Toshiko Tanaka, Reedik Mägi, Peter J van der Most, Anne U Jackson, Jennifer L Bragg-Gresham, Veronique Vitart, Jonathan Marten, Pau Navarro, Claire Bellis, Dorota Pasko, Åsa Johansson, Søren Snitker, Yu-Ching Cheng, Joel Eriksson, Unhee Lim, Mette Aadahl, Linda S Adair, Najaf Amin, Beverley Balkau, Juha Auvinen, John Beilby, Richard N Bergman, Sven Bergmann, Alain G Bertoni, John Blangero, Amélie Bonnefond, Lori L Bonnycastle, Judith B Borja, Søren Brage, Fabio Busonero, Steve Buyske, Harry Campbell, Peter S Chines, Francis S Collins, Tanguy Corre, George Davey Smith, Graciela E Delgado, Nicole Dueker, Marcus Dörr, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Jessica D Faul, Mao Fu, Kristine Færch, Christian Gieger, Sven Gläser, Jian Gong, Penny Gordon-Larsen, Harald Grallert, Tanja B Grammer, Niels Grarup, Gerard van Grootheest, Kennet Harald, Nicholas D Hastie, Aki S Havulinna, Dena Hernandez, Lucia Hindorff, Lynne J Hocking, Oddgeir L Holmens, Christina Holzapfel, Jouke Jan Hottenga, Jie Huang, Tao Huang, Jennie Hui, Cornelia Huth, Nina Hutri-Kähönen, Alan L James, John-Olov Jansson, Min A Jhun, Markus Juonala, Leena Kinnunen, Heikki A Koistinen, Ivana Kolcic, Pirjo Komulainen, Johanna Kuusisto, Kirsti Kvaløy, Mika Kähönen, Timo A Lakka, Lenore J Launer, Benjamin Lehne, Cecilia M Lindgren, Mattias Lorentzon, Robert Luben, Michel Marre, Yuri Milaneschi, Keri L Monda, Grant W Montgomery, Marleen H M De Moor, Antonella Mulas, Martina Müller-Nurasyid, A W Musk, Reija Männikkö, Satu Männistö, Narisu Narisu, Matthias Nauck, Jennifer A Nettleton, Ilja M Nolte, Albertine J Oldehinkel, Matthias Olden, Ken K Ong, Sandosh Padmanabhan, Lavinia Paternoster, Jeremiah Perez, Markus Perola, Annette Peters, Ulrike Peters, Patricia A Peyser, Inga Prokopenko, Hannu Puolijoki, Olli T Raitakari, Tuomo Rankinen, Laura J Rasmussen-Torvik, Rajesh Rawal, Paul M Ridker, Lynda M Rose, Igor Rudan, Cinzia Sarti, Mark A Sarzynski, Kai Savonen, William R Scott, Serena Sanna, Alan R Shuldiner, Steve Sidney, Günther Silbernagel, Blair H Smith, Jennifer A Smith, Harold Snieder, Alena Stančáková, Barbara Sternfeld, Amy J Swift, Tuija Tammelin, Sian-Tsung Tan, Barbara Thorand, Dorothée Thuillier, Liesbeth Vandenput, Henrik Vestergaard, Jana V van Vliet-Ostaptchouk, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Mark Walker, Sarah Wild, Andrew Wong, Alan F Wright, M Carola Zillikens, Niha Zubair, Christopher A Haiman, Loic Lemarchand, Ulf Gyllensten, Claes Ohlsson, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden, Louis Pérusse, James F Wilson, Caroline Hayward, Ozren Polasek, Francesco Cucca, Kristian Hveem, Catharina A Hartman, Anke Tönjes, Stefania Bandinelli, Lyle J Palmer, Sharon L R Kardia, Rainer Rauramaa, Thorkild I A Sørensen, Jaakko Tuomilehto, Veikko Salomaa, Brenda W J H Penninx, Eco J C de Geus, Dorret I Boomsma, Terho Lehtimäki, Massimo Mangino, Markku Laakso, Claude Bouchard, Nicholas G Martin, Diana Kuh, Yongmei Liu, Allan Linneberg, Winfried März, Konstantin Strauch, Mika Kivimäki, Tamara B Harris, Vilmundur Gudnason, Henry Völzke, Lu Qi, Marjo-Riitta Järvelin, John C Chambers, Jaspal S Kooner, Philippe Froguel, Charles Kooperberg, Peter Vollenweider, Göran Hallmans, Torben Hansen, Oluf Pedersen, Andres Metspalu, Nicholas J Wareham, Claudia Langenberg, David R Weir, David J Porteous, Eric Boerwinkle, Daniel I Chasman, Gonçalo R Abecasis, Inês Barroso, Mark I McCarthy, Timothy M Frayling, Jeffrey R O'Connell, Cornelia M van Duijn, Michael Boehnke, Iris M Heid, Karen L Mohlke, David P Strachan, Caroline S Fox, Ching-Ti Liu, Joel N Hirschhorn, Robert J Klein, Andrew D Johnson, Ingrid B Borecki, Paul W Franks, Kari E North, L Adrienne Cupples, Ruth J F Loos, Tuomas O Kilpeläinen
[This corrects the article DOI: 10.1371/journal.pgen.1006528.].
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28589358/somatic-hypermutation-and-affinity-maturation-analysis-using-the-4-hydroxy-3-nitrophenyl-acetyl-np-system
#9
Nicole Heise, Ulf Klein
Somatic hypermutation of immunoglobulin variable region (IgV) genes and affinity maturation of the antibody response are the hallmarks of the germinal center (GC) reaction in T cell-dependent immune responses. Determining the consequences of the experimental manipulation of the GC response on somatic hypermutation and affinity maturation requires the availability of a system that allows measuring these parameters. Immunization of mice of the C57/Bl6 genetic background with the hapten 4-hydroxy-3-nitrophenyl-acetyl (NP) coupled to a carrier protein leads to the predominant usage of one particular IgV heavy chain gene segment, V186...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28538790/challenges-for-conducting-blood-collection-and-biochemical-analysis-in-a-large-multicenter-school-based-study-with-adolescents-lessons-from-erica-in-brazil
#10
MULTICENTER STUDY
Felipe Vogt Cureau, Katia Vergetti Bloch, Aline Henz, Camila W Schaan, Carlos Henrique Klein, Cecília Lacroix de Oliveira, Denise Tavares Giannini, Elisa Brosina de Leon, Gabriela de Azevedo Abreu, Gabriela Heiden Telo, Glauber Monteiro Dias, Kênia Mara Baiocchi de Carvalho, Laura Augusta Barufaldi, Maria Cristina Caetano Kuschnir, Moyses Szklo, Renan Montenegro, Thiago Luiz Nogueira da Silva, Ulf Ekelund, Beatriz D Schaan
The Study of Cardiovascular Risk in Adolescents (ERICA) is a pioneering study that aimed to assess the prevalence of cardiovascular risk factors, including metabolic syndrome components in Brazilian adolescents. This study aims to describe the methodological aspects related to blood collection as well as to report pertaining results of the preparation, transport, storage, and exams in ERICA. Exams in ERICA were performed in a single laboratory and blood samples were collected in schools in a standardized manner...
May 18, 2017: Cadernos de Saúde Pública
https://www.readbyqxmd.com/read/28448500/genome-wide-physical-activity-interactions-in-adiposity-a-meta-analysis-of-200-452-adults
#11
Mariaelisa Graff, Robert A Scott, Anne E Justice, Kristin L Young, Mary F Feitosa, Llilda Barata, Thomas W Winkler, Audrey Y Chu, Anubha Mahajan, David Hadley, Luting Xue, Tsegaselassie Workalemahu, Nancy L Heard-Costa, Marcel den Hoed, Tarunveer S Ahluwalia, Qibin Qi, Julius S Ngwa, Frida Renström, Lydia Quaye, John D Eicher, James E Hayes, Marilyn Cornelis, Zoltan Kutalik, Elise Lim, Jian'an Luan, Jennifer E Huffman, Weihua Zhang, Wei Zhao, Paula J Griffin, Toomas Haller, Shafqat Ahmad, Pedro M Marques-Vidal, Stephanie Bien, Loic Yengo, Alexander Teumer, Albert Vernon Smith, Meena Kumari, Marie Neergaard Harder, Johanne Marie Justesen, Marcus E Kleber, Mette Hollensted, Kurt Lohman, Natalia V Rivera, John B Whitfield, Jing Hua Zhao, Heather M Stringham, Leo-Pekka Lyytikäinen, Charlotte Huppertz, Gonneke Willemsen, Wouter J Peyrot, Ying Wu, Kati Kristiansson, Ayse Demirkan, Myriam Fornage, Maija Hassinen, Lawrence F Bielak, Gemma Cadby, Toshiko Tanaka, Reedik Mägi, Peter J van der Most, Anne U Jackson, Jennifer L Bragg-Gresham, Veronique Vitart, Jonathan Marten, Pau Navarro, Claire Bellis, Dorota Pasko, Åsa Johansson, Søren Snitker, Yu-Ching Cheng, Joel Eriksson, Unhee Lim, Mette Aadahl, Linda S Adair, Najaf Amin, Beverley Balkau, Juha Auvinen, John Beilby, Richard N Bergman, Sven Bergmann, Alain G Bertoni, John Blangero, Amélie Bonnefond, Lori L Bonnycastle, Judith B Borja, Søren Brage, Fabio Busonero, Steve Buyske, Harry Campbell, Peter S Chines, Francis S Collins, Tanguy Corre, George Davey Smith, Graciela E Delgado, Nicole Dueker, Marcus Dörr, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Jessica D Faul, Mao Fu, Kristine Færch, Christian Gieger, Sven Gläser, Jian Gong, Penny Gordon-Larsen, Harald Grallert, Tanja B Grammer, Niels Grarup, Gerard van Grootheest, Kennet Harald, Nicholas D Hastie, Aki S Havulinna, Dena Hernandez, Lucia Hindorff, Lynne J Hocking, Oddgeir L Holmens, Christina Holzapfel, Jouke Jan Hottenga, Jie Huang, Tao Huang, Jennie Hui, Cornelia Huth, Nina Hutri-Kähönen, Alan L James, John-Olov Jansson, Min A Jhun, Markus Juonala, Leena Kinnunen, Heikki A Koistinen, Ivana Kolcic, Pirjo Komulainen, Johanna Kuusisto, Kirsti Kvaløy, Mika Kähönen, Timo A Lakka, Lenore J Launer, Benjamin Lehne, Cecilia M Lindgren, Mattias Lorentzon, Robert Luben, Michel Marre, Yuri Milaneschi, Keri L Monda, Grant W Montgomery, Marleen H M De Moor, Antonella Mulas, Martina Müller-Nurasyid, A W Musk, Reija Männikkö, Satu Männistö, Narisu Narisu, Matthias Nauck, Jennifer A Nettleton, Ilja M Nolte, Albertine J Oldehinkel, Matthias Olden, Ken K Ong, Sandosh Padmanabhan, Lavinia Paternoster, Jeremiah Perez, Markus Perola, Annette Peters, Ulrike Peters, Patricia A Peyser, Inga Prokopenko, Hannu Puolijoki, Olli T Raitakari, Tuomo Rankinen, Laura J Rasmussen-Torvik, Rajesh Rawal, Paul M Ridker, Lynda M Rose, Igor Rudan, Cinzia Sarti, Mark A Sarzynski, Kai Savonen, William R Scott, Serena Sanna, Alan R Shuldiner, Steve Sidney, Günther Silbernagel, Blair H Smith, Jennifer A Smith, Harold Snieder, Alena Stančáková, Barbara Sternfeld, Amy J Swift, Tuija Tammelin, Sian-Tsung Tan, Barbara Thorand, Dorothée Thuillier, Liesbeth Vandenput, Henrik Vestergaard, Jana V van Vliet-Ostaptchouk, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Mark Walker, Sarah Wild, Andrew Wong, Alan F Wright, M Carola Zillikens, Niha Zubair, Christopher A Haiman, Loic Lemarchand, Ulf Gyllensten, Claes Ohlsson, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden, Louis Pérusse, James F Wilson, Caroline Hayward, Ozren Polasek, Francesco Cucca, Kristian Hveem, Catharina A Hartman, Anke Tönjes, Stefania Bandinelli, Lyle J Palmer, Sharon L R Kardia, Rainer Rauramaa, Thorkild I A Sørensen, Jaakko Tuomilehto, Veikko Salomaa, Brenda W J H Penninx, Eco J C de Geus, Dorret I Boomsma, Terho Lehtimäki, Massimo Mangino, Markku Laakso, Claude Bouchard, Nicholas G Martin, Diana Kuh, Yongmei Liu, Allan Linneberg, Winfried März, Konstantin Strauch, Mika Kivimäki, Tamara B Harris, Vilmundur Gudnason, Henry Völzke, Lu Qi, Marjo-Riitta Järvelin, John C Chambers, Jaspal S Kooner, Philippe Froguel, Charles Kooperberg, Peter Vollenweider, Göran Hallmans, Torben Hansen, Oluf Pedersen, Andres Metspalu, Nicholas J Wareham, Claudia Langenberg, David R Weir, David J Porteous, Eric Boerwinkle, Daniel I Chasman, Gonçalo R Abecasis, Inês Barroso, Mark I McCarthy, Timothy M Frayling, Jeffrey R O'Connell, Cornelia M van Duijn, Michael Boehnke, Iris M Heid, Karen L Mohlke, David P Strachan, Caroline S Fox, Ching-Ti Liu, Joel N Hirschhorn, Robert J Klein, Andrew D Johnson, Ingrid B Borecki, Paul W Franks, Kari E North, L Adrienne Cupples, Ruth J F Loos, Tuomas O Kilpeläinen
Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28385374/central-immune-tolerance-depends-on-crosstalk-between-the-classical-and-alternative-nf-%C3%AE%C2%BAb-pathways-in-medullary-thymic-epithelial-cells
#12
Marc Riemann, Nico Andreas, Maria Fedoseeva, Elke Meier, Debra Weih, Helga Freytag, Ruth Schmidt-Ullrich, Ulf Klein, Zhao-Qi Wang, Falk Weih
Medullary thymic epithelial cells (mTECs) contribute to self-tolerance by expressing and presenting peripheral tissue antigens for negative selection of autoreactive T cells and differentiation of natural regulatory T cells. The molecular control of mTEC development remains incompletely understood. We here demonstrate by TEC-specific gene manipulation in mice that the NF-κB transcription factor subunit RelB, which is activated by the alternative NF-κB pathway, regulates development of mature mTECs in a dose-dependent manner...
July 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28300057/combined-toll-like-receptor-3-7-9-deficiency-on-host-cells-results-in-t-cell-dependent-control-of-tumour-growth
#13
Johanna C Klein, Katrin Moses, Gennadiy Zelinskyy, Simon Sody, Jan Buer, Stephan Lang, Iris Helfrich, Ulf Dittmer, Carsten J Kirschning, Sven Brandau
Toll-like receptors (TLRs) are located either on the cell surface or intracellularly in endosomes and their activation normally contributes to the induction of protective immune responses. However, in cancer their activation by endogenous ligands can modulate tumour progression. It is currently unknown how endosomal TLRs regulate endogenous anti-tumour immunity. Here we show that TLR3, 7 and 9 deficiencies on host cells, after initial tumour growth, result in complete tumour regression and induction of anti-tumour immunity...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28009285/anabolism-associated-mitochondrial-stasis-driving-lymphocyte-differentiation-over-self-renewal
#14
William C Adams, Yen-Hua Chen, Radomir Kratchmarov, Bonnie Yen, Simone A Nish, Wen-Hsuan W Lin, Nyanza J Rothman, Larry L Luchsinger, Ulf Klein, Meinrad Busslinger, Jeffrey C Rathmell, Hans-Willem Snoeck, Steven L Reiner
Regeneration requires related cells to diverge in fate. We show that activated lymphocytes yield sibling cells with unequal elimination of aged mitochondria. Disparate mitochondrial clearance impacts cell fate and reflects larger constellations of opposing metabolic states. Differentiation driven by an anabolic constellation of PI3K/mTOR activation, aerobic glycolysis, inhibited autophagy, mitochondrial stasis, and ROS production is balanced with self-renewal maintained by a catabolic constellation of AMPK activation, mitochondrial elimination, oxidative metabolism, and maintenance of FoxO1 activity...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27715077/nuclear-binding-near-a-quantum-phase-transition
#15
Serdar Elhatisari, Ning Li, Alexander Rokash, Jose Manuel Alarcón, Dechuan Du, Nico Klein, Bing-Nan Lu, Ulf-G Meißner, Evgeny Epelbaum, Hermann Krebs, Timo A Lähde, Dean Lee, Gautam Rupak
How do protons and neutrons bind to form nuclei? This is the central question of ab initio nuclear structure theory. While the answer may seem as simple as the fact that nuclear forces are attractive, the full story is more complex and interesting. In this work we present numerical evidence from ab initio lattice simulations showing that nature is near a quantum phase transition, a zero-temperature transition driven by quantum fluctuations. Using lattice effective field theory, we perform Monte Carlo simulations for systems with up to twenty nucleons...
September 23, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27701157/truncating-wilms-tumor-suppressor-gene-1-mutation-in-an-xx-female-with-adult-onset-focal-segmental-glomerulosclerosis-and-streak-ovaries-a-case-report
#16
Julia Hoefele, Markus J Kemper, Ulf Schoenermarck, Susanna Mueller, Hanns-Georg Klein, Anja Lemke
About 30% of children with nephrotic syndrome (NS) have inherited forms. Among them, mutations in Wilms tumor suppressor gene 1 (WT1) are a well characterized cause associated with steroid-resistant NS, Wilms tumor, and urogenital malformation in males. However, the role of WT1 mutations in adult-onset focal segmental glomerulosclerosis (FSGS) is unclear. We report the case of a 38-year-old female with FSGS. She had been diagnosed with streak ovaries during diagnostic workup for infertility. Mutational analysis identified the heterozygous mutation c...
2017: Nephron
https://www.readbyqxmd.com/read/27649781/differential-requirements-for-the-canonical-nf-%C3%AE%C2%BAb-transcription-factors-c-rel-and-rela-during-the-generation-and-activation-of-mature-b-cells
#17
Maja Milanovic, Nicole Heise, Nilushi S De Silva, Michael M Anderson, Kathryn Silva, Amanda Carette, Fabiano Orelli, Govind Bhagat, Ulf Klein
Signaling through the canonical nuclear factor-κB (NF-κB) pathway is critical for the generation and maintenance of mature B cells and for antigen-dependent B-cell activation. c-REL (rel) and RELA (rela) are the downstream transcriptional activators of the canonical NF-κB pathway. Studies of B cells derived from constitutional rel knockout mice and chimeric mice repopulated with rela-/- fetal liver cells provided evidence that the subunits can have distinct roles during B-cell development. However, the B cell-intrinsic functions of c-REL and RELA during B-cell generation and antigen-dependent B-cell activation have not been determined in vivo...
March 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27595233/an-essential-role-for-the-il-2-receptor-in-t-reg-cell-function
#18
Takatoshi Chinen, Arun K Kannan, Andrew G Levine, Xiying Fan, Ulf Klein, Ye Zheng, Georg Gasteiger, Yongqiang Feng, Jason D Fontenot, Alexander Y Rudensky
Regulatory T cells (Treg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Treg cells...
November 2016: Nature Immunology
https://www.readbyqxmd.com/read/27457956/transcription-factors-of-the-alternative-nf-%C3%AE%C2%BAb-pathway-are-required-for-germinal-center-b-cell-development
#19
Nilushi S De Silva, Michael M Anderson, Amanda Carette, Kathryn Silva, Nicole Heise, Govind Bhagat, Ulf Klein
The NF-κB signaling cascade relays external signals essential for B-cell growth and survival. This cascade is frequently hijacked by cancers that arise from the malignant transformation of germinal center (GC) B cells, underscoring the importance of deciphering the function of NF-κB in these cells. The NF-κB signaling cascade is comprised of two branches, the canonical and alternative NF-κB pathways, mediated by distinct transcription factors. The expression and function of the transcription factors of the alternative pathway, RELB and NF-κB2, in late B-cell development is incompletely understood...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27138529/multi-parametric-quantitative-mri-of-normal-appearing-white-matter-in-multiple-sclerosis-and-the-effect-of-disease-activity-on-t2
#20
Sarah C Reitz, Stephanie-Michelle Hof, Vinzenz Fleischer, Alla Brodski, Adriane Gröger, René-Maxime Gracien, Amgad Droby, Helmuth Steinmetz, Ulf Ziemann, Frauke Zipp, Ralf Deichmann, Johannes C Klein
White matter (WM) lesions with a distinct lesion-tissue contrast are the main radiological hallmark of multiple sclerosis (MS) in standard magnetic resonance imaging (MRI). Pathological WM changes beyond lesion development lack suitable contrasts, rendering the investigation of normal appearing WM (NAWM) more challenging. In this study, repeat quantitative MRI (qMRI) was collected in 9 relapsing remitting MS patients with mild disease over nine months. The relaxation times T1 and T2, the proton density (PD), and the magnetization transfer ratio (MTR) were analysed in the NAWM...
June 2017: Brain Imaging and Behavior
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