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61.
L Blanc SL Ciciotte B Gwynn GJ Hildick-Smith EL Pierce KA Soltis JD Cooney BH Paw LL Peters 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(30):12099-12104
Phenotype-driven approaches to gene discovery using inbred mice have been instrumental in identifying genetic determinants of inherited blood dyscrasias. The recessive mutant scat (severe combined anemia and thrombocytopenia) alternates between crisis and remission episodes, indicating an aberrant regulatory feedback mechanism common to erythrocyte and platelet formation. Here, we identify a missense mutation (G125V) in the scat Rasa3 gene, encoding a Ras GTPase activating protein (RasGAP), and elucidate the mechanism producing crisis episodes. The mutation causes mislocalization of RASA3 to the cytosol in scat red cells where it is inactive, leading to increased GTP-bound Ras. Erythropoiesis is severely blocked in scat crisis mice, and ~94% succumb during the second crisis (~30 d of age) from catastrophic hematopoietic failure in the spleen and bone marrow. Megakaryopoiesis is also defective during crisis. Notably, the scat phenotype is recapitulated in zebrafish when rasa3 is silenced. These results highlight a critical, conserved, and nonredundant role for RASA3 in vertebrate hematopoiesis. 相似文献
62.
63.
Couzi L Pitard V Sicard X Garrigue I Hawchar O Merville P Moreau JF Déchanet-Merville J 《Blood》2012,119(6):1418-1427
Human cytomegalovirus (HCMV) infection is an important cause of morbidity and mortality in transplant recipients. Long-term protective immunity against HCMV requires both sustained specific T-cell response and neutralizing IgG production, but the interplay between these effector arms remains poorly defined. We previously demonstrated that γδ T cells play a substantial role as anti-HCMV T-cell effectors. The observation that CD16 (FcγRIIIA) was specifically expressed by the majority of HCMV-induced γδ T cells prompted us to investigate their cooperation with anti-HCMV IgG. We found that CD16 could stimulate γδ T cells independently of T-cell receptor (TCR) engagement and provide them with an intrinsic antibody-dependent cell-mediated cytotoxic (ADCC) potential. Although CD16(+)γδ T cells did not mediate ADCC against HCMV-infected cells, in accordance with the low level of anti-HCMV IgGs recognizing infected cells, they produced IFNγ when incubated with IgG-opsonized virions. This CD16-induced IFNγ production was greatly enhanced by IL12 and IFNα, 2 cytokines produced during HCMV infection, and conferred to γδ T cells the ability to inhibit HCMV multiplication in vitro. Taken together, these data identify a new antiviral function for γδ T cells through cooperation with anti-HCMV IgG that could contribute to surveillance of HCMV reactivation in transplant recipients. 相似文献
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65.
Helga V. Toriello Miriam Erick Jean‐Luc Alessandri Diana Bailey Nicola Brunetti‐Pierri Helen Cox Alan Fryer Denise Marty Charles McCurdy John B. Mulliken Helen Murphy Joseph Omlor Richard M. Pauli Judith D. Ranells Amarillis Sanchez‐Valle Ana Tobiasz Lionel Van Maldergem Angela E. Lin 《American journal of medical genetics. Part A》2013,161(3):417-429
Chondrodysplasia punctata (CDP) is an etiologically heterogeneous disorder characterized by the radiographic finding of stippled epiphyses (punctate calcifications). It is often accompanied by a characteristic facial appearance, known as the Binder phenotype, which is attributed to hypoplasia of the nasal cartilages; abnormal distal phalanges (brachytelephalangy) are a common component manifestation as well. We report eight patients with a Binder phenotype with or without CDP who all shared a known or suspected maternal deficiency of vitamin K. We suspect that this phenotype is probably under recognized, and we hope to increase awareness about the maternal risk factors, especially hyperemesis gravidarum, which lead to nutritional deficiency. © 2013 Wiley Periodicals, Inc. 相似文献
66.
Katrina Tatton‐Brown Anne Murray Sandra Hanks Jenny Douglas Ruth Armstrong Siddharth Banka Lynne M. Bird Carol L. Clericuzio Valerie Cormier‐Daire Tom Cushing Frances Flinter Marie‐Line Jacquemont Shelagh Joss Esther Kinning Sally Ann Lynch Alex Magee Vivienne McConnell Ana Medeira Keiichi Ozono Michael Patton Julia Rankin Debbie Shears Marleen Simon Miranda Splitt Volker Strenger Kyra Stuurman Clare Taylor Hannah Titheradge Lionel Van Maldergem I. Karen Temple Trevor Cole Sheila Seal Childhood Overgrowth Consortium Nazneen Rahman 《American journal of medical genetics. Part A》2013,161(12):2972-2980
67.
In low- and middle-income countries, men who have sex with men (MSM) are 19 times more likely to be HIV positive compared with background populations. Criminalisation and social rejection of homosexuality in most sub-Saharan African countries reinforce stigma and exclude MSM from prevention activities, including HIV testing. This paper's purpose is to identify factors associated with never having been HIV tested (NHT), among a sample of Cameroonian MSM. In 2008, a community-based study was conducted in Douala, the economic capital city of Cameroon, by a local NGO Alternatives-Cameroun, recruiting participants through the snowball technique and administering a questionnaire during face-to-face interviews. Proximity to HIV was investigated according to the following criteria: knowing at least one person living with HIV and having been exposed to HIV prevention interventions. NHT was defined as reporting to have never been HIV tested. A logistic regression was used to identify factors associated with NHT. Among the 165 MSM of our study group who reported that they were not HIV positive, 19% reported NHT. Factors independently associated with NHT were as follows: being younger, being Muslim, not having a steady male partner, not knowing any person living with HIV and never having been exposed to HIV prevention interventions. In this MSM population, a small proportion reported that they had never been HIV tested and among these, the percentage was higher among individuals not in proximity to HIV. Despite the hostile context of sub-Saharan African countries towards MSM, local and national HIV testing campaigns to date may have played a substantial role in raising HIV awareness in the MSM population living in Douala, and peer-based counselling may have educated those in contact with Alternatives-Cameroun regarding the positive value of HIV testing. This result is a further argument for continuing community-based prevention and extending it to difficult-to-reach MSM. 相似文献
68.
Astrid Godron Jér?me Harambat Valérie Boccio Anne Mensire Adrien May Claire Rigothier Lionel Couzi Benoit Barrou Michel Godin Dominique Chauveau Stanislas Faguer Marion Vallet Pierre Cochat Philippe Eckart Geneviève Guest Vincent Guigonis Pascal Houillier Anne Blanchard Xavier Jeunemaitre Rosa Vargas-Poussou 《Clinical journal of the American Society of Nephrology》2012,7(5):801-809
69.
Joseph C. Klink Lionel L. Bañez Leah Gerber Amy Lark Robin T. Vollmer Stephen J. Freedland 《World journal of urology》2013,31(6):1497-1503