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Xin Yao, Chengrong Li, Jun Yang, Guobing Wang, Changgang Li, Yu Xia
OBJECTIVE: This study aims to investigate the role of T follicular helper (TFH) cells in the immunopathogenesis of pediatric immune thrombocytopenia (ITP), as well as differences in TFH expansion and its regulation between newly diagnosed ITP (nITP) and chronic pediatric ITP (cITP). METHODS: Eighty-five children with ITP and 20 age-matched healthy controls were enrolled into this study. TFH cell frequencies and TFH cell-associated regulatory factors before and after treatment were analyzed by flow cytometry, RT-PCR and ELISA...
October 2016: Blood Cells, Molecules & Diseases
Anissa Moktefi, Shao-Yu Zhang, Pauline Vachin, Virginie Ory, Carole Henique, Vincent Audard, Catherine Rucker-Martin, Elodie Gouadon, Michael Eccles, Andreas Schedl, Laurence Heidet, Mario Ollero, Djillali Sahali, Andre Pawlak
The WT1 (Wilm's tumor suppressor) gene is expressed throughout life in podocytes and is essential for the functional integrity of the glomerular filtration barrier. We have previously shown that CMIP (C-Maf inducing protein) is overproduced in podocyte diseases and alters intracellular signaling. Here we isolated the proximal region of the human CMIP promoter and showed by chromatin immunoprecipitation assays and electrophoretic-mobility shift that Wilm's tumor protein (WT1) bound to 2 WT1 response elements, located at positions -290/-274 and -57/-41 relative to transcription start site...
September 17, 2016: Kidney International
Hitomi Aoki, Hajime Ogino, Hiroyuki Tomita, Akira Hara, Takahiro Kunisada
REST (RE1-silencing transcription factor, also called Nrsf) is involved in the maintenance of the undifferentiated state of neuronal stem/progenitor cells in vitro by preventing precocious expression of neuronal genes. REST expression was then decreased in developing neurons to down-regulate neuronal genes which allow their maturation. However, the function of REST during neurogenesis in vivo remains to be elucidated because of the early embryonic lethal phenotype of conventional Rest knockout mice. In order to investigate the role of REST in ocular tissues, we generated and examined the mice evoking genetic ablation to Rest specifically to neural tissues including ocular tissue...
2016: PloS One
Mallika Pathania, Yan Wang, Vladimir N Simirskii, Melinda K Duncan
Integrins are heterodimeric cell surface molecules that mediate cell-extracellular matrix (ECM) adhesion, ECM assembly, and regulation of both ECM and growth factor induced signaling. However, the developmental context of these diverse functions is not clear. Loss of β1-integrin from the lens vesicle (mouse E10.5) results in abnormal exit of anterior lens epithelial cells (LECs) from the cell cycle and their aberrant elongation toward the presumptive cornea by E12.5. These cells lose expression of LEC markers and initiate expression of the Maf (also known as c-Maf) and Prox1 transcription factors as well as other lens fiber cell markers...
September 2, 2016: Differentiation; Research in Biological Diversity
Xiao-Rui Geng, Shu-Qi Qiu, Li-Tao Yang, Zhi-Qiang Liu, Gui Yang, Jiang-Qi Liu, Lu Zeng, Xiao-Xi Li, Li-Hua Mo, Zhi-Gang Liu, Ping-Chang Yang
Interleukin (IL)-10-expressing B cells play a critical role in the immune homeostasis in the body; its regulation has not been fully understood. Micro-RNA (miR)-17-92 cluster has strong regulation in the immunity. This study tests a hypothesis that miR-17-92 cluster suppresses IL-10 expression in B cells. In this study, peripheral B cells were collected from patients with allergic rhinitis (AR). The B cells were treated with specific allergens, dust mite extracts, in the culture. The expressions of miR-17-92 cluster and IL-10 in the culture were assessed by real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay...
August 2016: Cell Biochemistry and Function
Yumei Zhang, Yanjuan Wang, Yanyan Jiang, Wei Pan, Hua Liu, Jianhai Yin, Yujuan Shen, Jianping Cao
BACKGROUND: The role of T follicular helper (Tfh) cells in schistosome infection is not fully defined. In a previous study, a higher frequency of circulating PD-1(+)CXCR5(+)CD4(+) Tfh cells was observed in patients with chronic schistosomiasis relative to healthy controls (HCs) and it correlated positively with the level of soluble egg antigen (SEA) specific antibodies in serum. However, the function of Tfh cells in patients with acute schistosomiasis remains elusive; this was investigated in the present study...
2016: Parasites & Vectors
D Mesquita, W M Cruvinel, L S Resende, F V Mesquita, N P Silva, N O S Câmara, L E C Andrade
The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets...
2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Yan Borné, Martin Söderholm, Lars Barregard, Björn Fagerberg, Margaretha Persson, Olle Melander, Frank Thévenod, Bo Hedblad, Gunnar Engström
BACKGROUND: Cadmium is a non-essential toxic metal with multiple adverse health effects. Exposure in the general population occurs by smoking and diet. Cadmium in erythrocytes is a valid biomarker of exposure and body burden of cadmium. OBJECTIVES: We aimed to identify genetic variants related to concentrations of cadmium in erythrocytes. METHODS: Erythrocyte cadmium was analyzed in 4432 individuals (1728 never smokers) from the Swedish population-based Malmö Diet and Cancer cohort...
March 22, 2016: Human Molecular Genetics
Dhouha Daassi, Michito Hamada, Hyojung Jeon, Yuki Imamura, Mai Thi Nhu Tran, Satoru Takahashi
The large Maf transcription factors c-Maf and MafB are expressed in macrophage-lineage hematopoietic cells, but the expression patterns of MafB and c-Maf in macrophage subtypes and tissue-resident macrophages have not been fully analyzed. First, we analyzed MafB and c-Maf protein expression in tissue-resident macrophages. Mouse lymph nodes, spleens, lungs, and kidneys were subjected to immunohistochemistry using anti-MafB and anti-c-Maf. Both MafB and c-Maf signals were observed in lymph node macrophages. In the splenic macrophages the MafB signal was detected by anti-MafB, but the c-Maf signal was not detected...
April 22, 2016: Biochemical and Biophysical Research Communications
Deepti Anand, Salil A Lachke
Over the past several decades, the biology of the developing lens has been investigated using molecular genetics-based approaches in various vertebrate model systems. These efforts, involving target gene knockouts or knockdowns, have led to major advances in our understanding of lens morphogenesis and the pathological basis of cataracts, as well as of other lens related eye defects. In particular, we now have a functional understanding of regulators such as Pax6, Six3, Sox2, Oct1 (Pou2f1), Meis1, Pnox1, Zeb2 (Sip1), Mab21l1, Foxe3, Tfap2a (Ap2-alpha), Pitx3, Sox11, Prox1, Sox1, c-Maf, Mafg, Mafk, Hsf4, Fgfrs, Bmp7, and Tdrd7 in this tissue...
March 15, 2016: Experimental Eye Research
Heping Yang, Ting Liu, Jiaohong Wang, Tony W H Li, Wei Fan, Hui Peng, Anuradha Krishnan, Gregory J Gores, Jose M Mato, Shelly C Lu
UNLABELLED: c-Myc induction drives cholestatic liver injury and cholangiocarcinoma (CCA) in mice, and induction of Maf proteins (MafG and c-Maf) contributes to cholestatic liver injury, whereas S-adenosylmethionine (SAMe) administration is protective. Here, we determined whether there is interplay between c-Myc, Maf proteins, and methionine adenosyltransferase α1 (MATα1), which is responsible for SAMe biosynthesis in the liver. We used bile duct ligation (BDL) and lithocholic acid (LCA) treatment in mice as chronic cholestasis models, a murine CCA model, human CCA cell lines KMCH and Huh-28, human liver cancer HepG2, and human CCA specimens to study gene and protein expression, protein-protein interactions, molecular mechanisms, and functional outcomes...
August 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Wook-Jin Chae, Allison K Ehrlich, Pamela Y Chan, Alexandra M Teixeira, Octavian Henegariu, Liming Hao, Jae Hun Shin, Jong-Hyun Park, Wai Ho Tang, Sang-Taek Kim, Stephen E Maher, Karen Goldsmith-Pestana, Peiying Shan, John Hwa, Patty J Lee, Diane S Krause, Carla V Rothlin, Diane McMahon-Pratt, Alfred L M Bothwell
Exposure to a plethora of environmental challenges commonly triggers pathological type 2 cell-mediated inflammation. Here we report the pathological role of the Wnt antagonist Dickkopf-1 (Dkk-1) upon allergen challenge or non-healing parasitic infection. The increased circulating amounts of Dkk-1 polarized T cells to T helper 2 (Th2) cells, stimulating a marked simultaneous induction of the transcription factors c-Maf and Gata-3, mediated by the kinases p38 MAPK and SGK-1, resulting in Th2 cell cytokine production...
February 16, 2016: Immunity
Erinn L Soucie, Ziming Weng, Laufey Geirsdóttir, Kaaweh Molawi, Julien Maurizio, Romain Fenouil, Noushine Mossadegh-Keller, Gregory Gimenez, Laurent VanHille, Meryam Beniazza, Jeremy Favret, Carole Berruyer, Pierre Perrin, Nir Hacohen, J-C Andrau, Pierre Ferrier, Patrice Dubreuil, Arend Sidow, Michael H Sieweke
Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors...
February 12, 2016: Science
Qing Xie, Rebecca McGreal, Raven Harris, Chun Y Gao, Wei Liu, Lixing W Reneker, Linda S Musil, Ales Cvekl
Fibroblast growth factor (FGF) signaling regulates a multitude of cellular processes, including cell proliferation, survival, migration, and differentiation. In the vertebrate lens, FGF signaling regulates fiber cell differentiation characterized by high expression of crystallin proteins. However, a direct link between FGF signaling and crystallin gene transcriptional machinery remains to be established. Previously, we have shown that the bZIP proto-oncogene c-Maf regulates expression of αA-crystallin (Cryaa) through binding to its promoter and distal enhancer, DCR1, both activated by FGF2 in cell culture...
February 19, 2016: Journal of Biological Chemistry
Félicien Moukambi, Henintsoa Rabezanahary, Vasco Rodrigues, Gina Racine, Lynda Robitaille, Bernard Krust, Guadalupe Andreani, Calayselvy Soundaramourty, Ricardo Silvestre, Mireille Laforge, Jérôme Estaquier
Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter...
December 2015: PLoS Pathogens
Yasushi Adachi, Takuya Hino, Masahiko Ohsawa, Kazuhito Ueki, Tomoko Murao, Ming Li, Yunze Cui, Mitsuhiko Okigaki, Mitsuhiro Ito, Susumu Ikehara
Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell lymphoma, known to express CD3 and CD4, and, frequently, also CD10 and c-Maf-1. Hypergammaglobulinemia is not particularly rare in patients with AITL. However, AITL in conjunction with plasmacytosis in the peripheral blood is rare. The current report presents a case of CD10-negative AITL demonstrating leukemic change and plasmacytosis in the peripheral blood mimicking plasma cell leukemia. A 78-year-old male was admitted to hospital due to systemic lymph node enlargement, high serum IgG and IgA, and increased counts of plasmacytoid cells and lymphoid cells with atypical nuclei in the peripheral blood...
September 2015: Oncology Letters
Chun-Mei Wang, Yuan Luo, Ying-Chao Wang, Guang-Yao Sheng
OBJECTIVE: To study the roles of follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells in the pathogenesis of Henoch-Schönlein purpura (HSP) in children. METHODS: Peripheral blood samples were collected from 40 HSP children and 25 healthy controls. The percentages of Tfh and Tfr cells were measured by flow cytometry; the mRNA expression levels of Bcl-6, c-MAF, Blimp-1, and PD-1 in peripheral blood were measured by real-time polymerase chain reaction...
October 2015: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Jeffery D Ray, Arun Prabhu Dhanapal, Shardendu K Singh, Valerio Hoyos-Villegas, James R Smith, Larry C Purcell, C Andy King, Debbie Boykin, Perry B Cregan, Qijian Song, Felix B Fritschi
Ureides are the N-rich products of N-fixation that are transported from soybean nodules to the shoot. Ureides are known to accumulate in leaves in response to water-deficit stress, and this has been used to identify genotypes with reduced N-fixation sensitivity to drought. Our objectives in this research were to determine shoot ureide concentrations in 374 Maturity Group IV soybean accessions and to identify genomic regions associated with shoot ureide concentration. The accessions were grown at two locations (Columbia, MO, and Stuttgart, AR) in 2 yr (2009 and 2010) and characterized for ureide concentration at beginning flowering to full bloom...
November 2015: G3: Genes—Genomes—Genetics
Hou-Feng Zheng, Vincenzo Forgetta, Yi-Hsiang Hsu, Karol Estrada, Alberto Rosello-Diez, Paul J Leo, Chitra L Dahia, Kyung Hyun Park-Min, Jonathan H Tobias, Charles Kooperberg, Aaron Kleinman, Unnur Styrkarsdottir, Ching-Ti Liu, Charlotta Uggla, Daniel S Evans, Carrie M Nielson, Klaudia Walter, Ulrika Pettersson-Kymmer, Shane McCarthy, Joel Eriksson, Tony Kwan, Mila Jhamai, Katerina Trajanoska, Yasin Memari, Josine Min, Jie Huang, Petr Danecek, Beth Wilmot, Rui Li, Wen-Chi Chou, Lauren E Mokry, Alireza Moayyeri, Melina Claussnitzer, Chia-Ho Cheng, Warren Cheung, Carolina Medina-Gómez, Bing Ge, Shu-Huang Chen, Kwangbom Choi, Ling Oei, James Fraser, Robert Kraaij, Matthew A Hibbs, Celia L Gregson, Denis Paquette, Albert Hofman, Carl Wibom, Gregory J Tranah, Mhairi Marshall, Brooke B Gardiner, Katie Cremin, Paul Auer, Li Hsu, Sue Ring, Joyce Y Tung, Gudmar Thorleifsson, Anke W Enneman, Natasja M van Schoor, Lisette C P G M de Groot, Nathalie van der Velde, Beatrice Melin, John P Kemp, Claus Christiansen, Adrian Sayers, Yanhua Zhou, Sophie Calderari, Jeroen van Rooij, Chris Carlson, Ulrike Peters, Soizik Berlivet, Josée Dostie, Andre G Uitterlinden, Stephen R Williams, Charles Farber, Daniel Grinberg, Andrea Z LaCroix, Jeff Haessler, Daniel I Chasman, Franco Giulianini, Lynda M Rose, Paul M Ridker, John A Eisman, Tuan V Nguyen, Jacqueline R Center, Xavier Nogues, Natalia Garcia-Giralt, Lenore L Launer, Vilmunder Gudnason, Dan Mellström, Liesbeth Vandenput, Najaf Amin, Cornelia M van Duijn, Magnus K Karlsson, Östen Ljunggren, Olle Svensson, Göran Hallmans, François Rousseau, Sylvie Giroux, Johanne Bussière, Pascal P Arp, Fjorda Koromani, Richard L Prince, Joshua R Lewis, Bente L Langdahl, A Pernille Hermann, Jens-Erik B Jensen, Stephen Kaptoge, Kay-Tee Khaw, Jonathan Reeve, Melissa M Formosa, Angela Xuereb-Anastasi, Kristina Åkesson, Fiona E McGuigan, Gaurav Garg, Jose M Olmos, Maria T Zarrabeitia, Jose A Riancho, Stuart H Ralston, Nerea Alonso, Xi Jiang, David Goltzman, Tomi Pastinen, Elin Grundberg, Dominique Gauguier, Eric S Orwoll, David Karasik, George Davey-Smith, Albert V Smith, Kristin Siggeirsdottir, Tamara B Harris, M Carola Zillikens, Joyce B J van Meurs, Unnur Thorsteinsdottir, Matthew T Maurano, Nicholas J Timpson, Nicole Soranzo, Richard Durbin, Scott G Wilson, Evangelia E Ntzani, Matthew A Brown, Kari Stefansson, David A Hinds, Tim Spector, L Adrienne Cupples, Claes Ohlsson, Celia M T Greenwood, Rebecca D Jackson, David W Rowe, Cynthia A Loomis, David M Evans, Cheryl L Ackert-Bicknell, Alexandra L Joyner, Emma L Duncan, Douglas P Kiel, Fernando Rivadeneira, J Brent Richards
The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population...
October 1, 2015: Nature
Marco Petrillo, Gian Franco Zannoni, Enrica Martinelli, Luigi Pedone Anchora, Gabriella Ferrandina, Giovanna Tropeano, Anna Fagotti, Giovanni Scambia
OBJECTIVE: We investigate the prognostic role of pre-treatment ratio between Type 1 (M1) and Type 2 (M2) tumor-associated macrophages (TAMs) in locally advanced cervical cancer (LACC) patients treated with chemoradiation (CT/RT). METHODS: 84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose of 50.0 Gy, followed by radical surgery were analysed. Double-staining immunohistochemistry of CD163/p-STAT, CD68/pSTAT1, CD163/c-MAF, and CD68/c-MAF was performed on tumor samples taken at the time of diagnosis...
2015: PloS One
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