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https://www.readbyqxmd.com/read/28589358/somatic-hypermutation-and-affinity-maturation-analysis-using-the-4-hydroxy-3-nitrophenyl-acetyl-np-system
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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-treg-cell-function
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27119439/pharmacokinetics-and-pharmacodynamics-of-canakinumab-in-patients-with-systemic-juvenile-idiopathic-arthritis
#13
Haiying Sun, Linh M Van, David Floch, Xuemin Jiang, Ulf R Klein, Ken Abrams, Gangadhar Sunkara
The characterization of the pharmacokinetic (PK) and pharmacodynamic (PD) properties in pediatric patients is essential in supporting the recommended dosage of canakinumab in the relevant population. Here the PK and PD properties of canakinumab-a monoclonal antibody-in pediatric patients with systemic juvenile idiopathic arthritis (SJIA) are presented. Blood samples were obtained from 4 phase 2/3 clinical studies in patients with SJIA. Canakinumab PK properties and total interleukin (IL)-1β kinetic properties were characterized by a population-based PK-binding model...
December 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/26982364/nemo-prevents-rip-kinase-1-mediated-epithelial-cell-death-and-chronic-intestinal-inflammation-by-nf-%C3%AE%C2%BAb-dependent-and-independent-functions
#14
Katerina Vlantis, Andy Wullaert, Apostolos Polykratis, Vangelis Kondylis, Marius Dannappel, Robin Schwarzer, Patrick Welz, Teresa Corona, Henning Walczak, Falk Weih, Ulf Klein, Michelle Kelliher, Manolis Pasparakis
Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions...
March 15, 2016: Immunity
https://www.readbyqxmd.com/read/26916719/multiplexed-pancreatic-genome-engineering-and-cancer-induction-by-transfection-based-crispr-cas9-delivery-in-mice
#15
Roman Maresch, Sebastian Mueller, Christian Veltkamp, Rupert Öllinger, Mathias Friedrich, Irina Heid, Katja Steiger, Julia Weber, Thomas Engleitner, Maxim Barenboim, Sabine Klein, Sandra Louzada, Ruby Banerjee, Alexander Strong, Teresa Stauber, Nina Gross, Ulf Geumann, Sebastian Lange, Marc Ringelhan, Ignacio Varela, Kristian Unger, Fengtang Yang, Roland M Schmid, George S Vassiliou, Rickmer Braren, Günter Schneider, Mathias Heikenwalder, Allan Bradley, Dieter Saur, Roland Rad
Mouse transgenesis has provided fundamental insights into pancreatic cancer, but is limited by the long duration of allele/model generation. Here we show transfection-based multiplexed delivery of CRISPR/Cas9 to the pancreas of adult mice, allowing simultaneous editing of multiple gene sets in individual cells. We use the method to induce pancreatic cancer and exploit CRISPR/Cas9 mutational signatures for phylogenetic tracking of metastatic disease. Our results demonstrate that CRISPR/Cas9-multiplexing enables key applications, such as combinatorial gene-network analysis, in vivo synthetic lethality screening and chromosome engineering...
February 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/26851215/impairment-of-mature-b-cell-maintenance-upon-combined-deletion-of-the-alternative-nf-%C3%AE%C2%BAb-transcription-factors-relb-and-nf-%C3%AE%C2%BAb2-in-b-cells
#16
Nilushi S De Silva, Kathryn Silva, Michael M Anderson, Govind Bhagat, Ulf Klein
BAFF is critical for the survival and maturation of mature B cells. BAFF, via BAFFR, activates multiple signaling pathways in B cells, including the alternative NF-κB pathway. The transcription factors RELB and NF-κB2 (p100/p52) are the downstream mediators of the alternative pathway; however, the B cell-intrinsic functions of these NF-κB subunits have not been studied in vivo using conditional alleles, either individually or in combination. We in this study report that B cell-specific deletion of relb led to only a slight decrease in the fraction of mature splenic B cells, whereas deletion of nfkb2 caused a marked reduction...
March 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26802176/melphalan-prednisone-and-lenalidomide-versus-melphalan-prednisone-and-thalidomide-in-untreated-multiple-myeloma
#17
RANDOMIZED CONTROLLED TRIAL
Sonja Zweegman, Bronno van der Holt, Ulf-Henrik Mellqvist, Morten Salomo, Gerard M J Bos, Mark-David Levin, Heleen Visser-Wisselaar, Markus Hansson, Annette W G van der Velden, Wendy Deenik, Astrid Gruber, Juleon L L M Coenen, Torben Plesner, Saskia K Klein, Bea C Tanis, Damian L Szatkowski, Rolf E Brouwer, Matthijs Westerman, M Rineke B L Leys, Harm A M Sinnige, Einar Haukås, Klaas G van der Hem, Marc F Durian, E Vera J M Mattijssen, Niels W C J van de Donk, Marian J P L Stevens-Kroef, Pieter Sonneveld, Anders Waage
The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R)...
March 3, 2016: Blood
https://www.readbyqxmd.com/read/26628372/asymmetric-pi3k-signaling-driving-developmental-and-regenerative-cell-fate-bifurcation
#18
Wen-Hsuan W Lin, William C Adams, Simone A Nish, Yen-Hua Chen, Bonnie Yen, Nyanza J Rothman, Radomir Kratchmarov, Takaharu Okada, Ulf Klein, Steven L Reiner
Metazoan sibling cells often diverge in activity and identity, suggesting links between growth signals and cell fate. We show that unequal transduction of nutrient-sensitive PI3K/AKT/mTOR signaling during cell division bifurcates transcriptional networks and fates of kindred cells. A sibling B lymphocyte with stronger signaling, indexed by FoxO1 inactivation and IRF4 induction, undergoes PI3K-driven Pax5 repression and plasma cell determination, while its sibling with weaker PI3K activity renews a memory or germinal center B cell fate...
December 15, 2015: Cell Reports
https://www.readbyqxmd.com/read/26555174/nemo-prevents-steatohepatitis-and-hepatocellular-carcinoma-by-inhibiting-ripk1-kinase-activity-mediated-hepatocyte-apoptosis
#19
Vangelis Kondylis, Apostolos Polykratis, Hanno Ehlken, Laura Ochoa-Callejero, Beate Katharina Straub, Santosh Krishna-Subramanian, Trieu-My Van, Harald-Morten Curth, Nicole Heise, Falk Weih, Ulf Klein, Peter Schirmacher, Michelle Kelliher, Manolis Pasparakis
IκB kinase/nuclear [corrected] factor κB (IKK/NF-κB) signaling exhibits important yet opposing functions in hepatocarcinogenesis. Mice lacking NEMO in liver parenchymal cells (LPC) spontaneously develop steatohepatitis and hepatocellular carcinoma (HCC) suggesting that NF-κB prevents liver disease and cancer. Here, we show that complete NF-κB inhibition by combined LPC-specific ablation of RelA, c-Rel, and RelB did not phenocopy NEMO deficiency, but constitutively active IKK2-mediated NF-κB activation prevented hepatocellular damage and HCC in NEMO(LPC-KO) mice...
November 9, 2015: Cancer Cell
https://www.readbyqxmd.com/read/26553579/changes-in-brain-functional-connectivity-patterns-are-driven-by-an-individual-lesion-in-ms-a-resting-state-fmri-study
#20
Amgad Droby, Kenneth S L Yuen, Muthuraman Muthuraman, Sarah-Christina Reitz, Vinzenz Fleischer, Johannes Klein, René-Maxime Gracien, Ulf Ziemann, Ralf Deichmann, Frauke Zipp, Sergiu Groppa
Diffuse inflammation in multiple sclerosis (MS) extends beyond focal lesion sites, affecting interconnected regions; however, little is known about the impact of an individual lesion affecting major white matter (WM) pathways on brain functional connectivity (FC). Here, we longitudinally assessed the effects of acute and chronic lesions on FC in relapsing-remitting MS (RRMS) patients using resting-state fMRI. 45 MRI data sets from 9 RRMS patients were recorded using 3T MR scanner over 5 time points at 8 week intervals...
December 2016: Brain Imaging and Behavior
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