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排序方式: 共有92条查询结果,搜索用时 31 毫秒
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Erik Schoenmakers Bradley Carlson Maura Agostini Carla Moran Odelia Rajanayagam Elena Bochukova Ryuta Tobe Rachel Peat Evelien Gevers Francesco Muntoni Pascale Guicheney Nadia Schoenmakers Sadaf Farooqi Greta Lyons Dolph Hatfield Krishna Chatterjee 《The Journal of clinical investigation》2016,126(3):992-996
Selenium is a trace element that is essential for human health and is incorporated into more than 25 human selenocysteine-containing (Sec-containing) proteins via unique Sec-insertion machinery that includes a specific, nuclear genome–encoded, transfer RNA (tRNA[Ser]Sec). Here, we have identified a human tRNA[Ser]Sec mutation in a proband who presented with a variety of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress-related, but not housekeeping, selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress-related selenoprotein production is likely mediated by reduced expression and diminished 2′-O-methylribosylation at uridine 34 in mutant tRNA[Ser]Sec. Moreover, this methylribosylation defect was restored by cellular complementation with normal tRNA[Ser]Sec. This study identifies a tRNA mutation that selectively impairs synthesis of stress-related selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis. 相似文献
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Xu XM Turanov AA Carlson BA Yoo MH Everley RA Nandakumar R Sorokina I Gygi SP Gladyshev VN Hatfield DL 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(50):21430-21434
Cysteine (Cys) is inserted into proteins in response to UGC and UGU codons. Herein, we show that supplementation of mammalian cells with thiophosphate led to targeted insertion of Cys at the UGA codon of thioredoxin reductase 1 (TR1). This Cys was synthesized by selenocysteine (Sec) synthase on tRNA([Ser]Sec) and its insertion was dependent on the Sec insertion sequence element in the 3'UTR of TR1 mRNA. The substrate for this reaction, thiophosphate, was synthesized by selenophosphate synthetase 2 from ATP and sulfide and reacted with phosphoseryl-tRNA([Ser]Sec) to generate Cys-tRNA([Ser]Sec). Cys was inserted in vivo at UGA codons in natural mammalian TRs, and this process was regulated by dietary selenium and availability of thiophosphate. Cys occurred at 10% of the Sec levels in liver TR1 of mice maintained on a diet with normal amounts of selenium and at 50% in liver TR1 of mice maintained on a selenium deficient diet. These data reveal a novel Sec machinery-based mechanism for biosynthesis and insertion of Cys into protein at UGA codons and suggest new biological functions for thiophosphate and sulfide in mammals. 相似文献
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Chianchiano D 《Advances in Chronic Kidney Disease》2008,15(2):174-176
Two dozen states have undertaken initiatives to address chronic kidney disease (CKD), with the goal of facilitating early identification of CKD and intervention to prevent the progression of CKD and its comorbidities. Each state has approached this goal in a different fashion. The impact of these varying initiatives should be evaluated so as to guide policy development in other jurisdictions. 相似文献
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Pancreatic undifferentiated carcinoma with osteoclast‐like giant cells is genetically similar to,but clinically distinct from,conventional ductal adenocarcinoma
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Claudio Luchini Antonio Pea Gemma Lionheart Andrea Mafficini Alessia Nottegar Nicola Veronese Peter Chianchiano Lodewijk AA Brosens Michaël Noë G Johan A Offerhaus Raluca Yonescu Yi Ning Giuseppe Malleo Giulio Riva Paola Piccoli Ivana Cataldo Paola Capelli Giuseppe Zamboni Aldo Scarpa Laura D Wood 《The Journal of pathology》2017,243(2):148-154
Undifferentiated carcinoma of the pancreas with osteoclast‐like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well‐defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
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A Perino C Cimino C Pignatone A Borruso N Chianchiano G Bertolino A Biondo P Costa E Cittadini R Marcenò 《Acta Europaea fertilitatis》1991,22(3):171-175
The Authors record the results in a group of patients with immunologic recurrent abortion (IRA) treated with two different immunoprophylaxis regimen. The first one is an active prophylaxis therapy with preparation and administration from donor mononucleates. According to their previous original experience, the Authors started giving high doses of IV-Ig (HD IV-Ig) in a second group of pregnant patients with the same diagnosis of immunologic recurrent abortion (IRA). The results of this not randomized study show better reproductive outcome in the group treated with use of HD IV-Ig. 相似文献
9.
Dolph Hatfield 《Proceedings of the National Academy of Sciences of the United States of America》1972,69(10):3014-3018
The tritiated trinucleotide UGA was used in a binding assay to detect transfer RNAs that recognize this nonsense codon from calf-liver cells. Acylation of transfer RNA with labeled amino acids and determination of codon responses of aminoacyl-tRNAs demonstrate that a species of seryl-tRNA and a species of arginyl-tRNA recognize the codon UGA. Slight responses of cysteinyl-tRNA and of trytophanyl-tRNA to the codon UGA were also observed. 相似文献
10.
Chianchiano D 《Advances in Chronic Kidney Disease》2006,13(2):189-191
The Uniform Anatomical Gift Act (UAGA) and its periodic revisions provide a template for the creation and amendment of legislation to adjust public policy and align it with developments in medical practice. It is also a model for statutory response to societal change as well as changes in regulatory and judicial precedents. Conversely, the history of the UAGA shows the limits of legislation to achieve certain social goals. 相似文献