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排序方式: 共有334条查询结果,搜索用时 15 毫秒
191.
192.
Das J Liu C Moquin RV Lin J Furch JA Spergel SH Doweyko AM McIntyre KW Shuster DJ O'Day KD Penhallow B Hung CY Kanner SB Lin TA Dodd JH Barrish JC Wityak J 《Bioorganic & medicinal chemistry letters》2006,16(9):2411-2415
A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 2 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo. 相似文献
193.
AE Clarke S Bernatsky KH Costenbader MB Urowitz DD Gladman PR Fortin M Petri S Manzi DA Isenberg A Rahman D Wallace C Gordon C Peschken MA Dooley EM Ginzler C Aranow SM Edworthy O Nived S Jacobsen G Ruiz-Irastorza E Yelin SG Barr L Criswell G Sturfelt L Dreyer I Blanco L Gottesman CH Feldman R Ramsey-Goldman 《Arthritis research & therapy》2012,14(Z3):A16
194.
Two groups of chickens (Gallus domesticus; White Leghorn; age, 4 d and 2 wk) housed in a university research vivarium were found dead or moribund without prior signs of illness. The overall mortality rates were 92.3% (60 of 65 birds) for the 4-d-old birds and 80% (8 of 10) for the 2-wk-old birds. All chicks were housed in brooders with heat lamps in a temperature- and humidity-controlled room. Primary gross findings were mild to moderate dehydration and hepatic lipidosis. The most consistent histologic findings were pulmonary hemorrhage and edema in all 7 of the 4-d-old birds evaluated and in all 4 of the 2-wk-old birds assessed. In addition, 1 of the 4-d-old birds had multifocal centrilobular hepatic necrosis. These findings suggested an inhaled toxicant and hypoxia, respectively. Inspection of the animal room revealed that approximately 50% of the heat lamp bulbs in the brooder cage were coated with polytetrafluoroethylene (PTFE). Two published case reports detail similar experiences in birds exposed to PTFE-coated heat-lamp bulbs. Birds are highly sensitive to inhaled toxicants owing to the high efficiency of their respiratory systems, and PTFE toxicosis is known to cause pulmonary edema and hemorrhage in pet birds after exposure to overheated nonstick cookware. In the present case, the bulbs were replaced, and no similar problems subsequently have been noted. This case illustrates the sensitivity of avian species to respiratory toxicants and serves as a reminder that toxicosis can be encountered even in the controlled environment of a laboratory vivarium. 相似文献
195.
Jayne E Rattray Marc Strous Huub JM Op den Camp Stefan Schouten Mike SM Jetten Jaap S Sinninghe Damsté 《Biology direct》2009,4(1):8-16
Background
The fatty acids of anaerobic ammonium oxidizing (anammox) bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway. 相似文献196.
Lori Jo Wilmeth Sanjay Shrestha Gilbert Monta?o Jennifer Rashe Charles Bradley Shuster 《Molecular biology of the cell》2010,21(3):380-392
The spatial and temporal coordination of chromosome segregation with cytokinesis is essential to ensure that each daughter cell receives the correct complement of chromosomal and cytoplasmic material. In yeast, mitotic exit and cytokinesis are coordinated by signaling cascades whose terminal components include a nuclear Dbf2-related family kinase and a noncatalytic subunit, Mps one binding (Mob) 1. There are five human Mob1 isoforms, all of which display redundant localization patterns at the spindle poles and kinetochores in early mitosis, and the spindle midzone during cytokinesis. Mob1 shares similar localization patterns to Polo-like kinase (Plk1) and the chromosomal passenger complex (CPC), and although depletion of Plk1 resulted in a loss of Mob1 from the spindle poles, Mob1 recruitment to kinetochores was unaffected. Conversely, disruption of CPC signaling resulted in a loss of Mob1 from kinetochores without disrupting recruitment to the spindle poles. In Mob1-depleted cells, the relocalization of the CPC and mitotic kinesin-like protein (MKLP) 2 to the spindle midzone was delayed during early anaphase, and as a consequence, the midzone recruitment of MKLP1 also was affected. Together, these results suggest that Mob1 and the other mammalian orthologues of the mitotic exit network regulate mitotic progression by facilitating the timely mobilization of the CPC to the spindle midzone. 相似文献
197.
N. V. Kononova A. I. Bobruskin T. I. Kostromina T. D. Melikhova A. A. Vainson E. V. Sveshnikova A. A. Zinchenko A. V. Demin V. A. Martyanov A. M. Shuster D. I. Bairamashvili 《Applied Biochemistry and Microbiology》2010,46(7):726-732
Technology of industrial production of an active pharmaceutical substance (APS) of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) involved the use of a highly productive E. coli strain capable of biosynthesis of rhG-CSF in the form of inclusion bodies (IB). A method of strain cultivation has been described, and methods of IB isolation, industrial-scale purification, filgrastim APS production, and quality control have been developed. Clinical trials of the preparation, carried out in the leading Russian clinics, were successful. Efficiency and safety of the preparation have been confirmed. A ready pharmaceutical form Neupomax® been produced in Russia since 2008 according to the technology developed. 相似文献
198.
199.
Lawrence H. Pinto Emily Eaton Bohao Chen Jonah Fleisher Dmitry Shuster Joel McCauley Dalius Kedainis Sandra M. Siepka Kazuhiro Shimomura Eun-Joo Song Aliya Husain Oren J. Lakser Richard W. Mitchell Maria L. Dowell Melanie Brown Blanca Camoretti-Mercado Robert Naclerio Anne I. Sperling Stephen I. Levin Fred W. Turek Julian Solway 《Mammalian genome》2008,19(1):2-14
We mutagenized male BTBR mice with N-ethyl-N-nitrosourea and screened 1315 of their G3 offspring for airway hyperresponsiveness.
A phenovariant G3 mouse with exaggerated methacholine bronchoconstrictor response was identified and his progeny bred in a
nonspecific-pathogen-free (SPF) facility where sentinels tested positive for minute virus of mice and mouse parvovirus and
where softwood bedding was used. The mutant phenotype was inherited through G11 as a single autosomal semidominant mutation
with marked gender restriction, with males exhibiting almost full penetrance and very few females phenotypically abnormal.
Between G11 and G12, facility infection eradication was undertaken and bedding was changed to hardwood. We could no longer
detect airway hyperresponsiveness in more than 37 G12 offspring of 26 hyperresponsive G11 males. Also, we could not identify
the mutant phenotype among offspring of hyperresponsive G8–G10 sires rederived into an SPF facility despite 21 attempts. These
two observations suggest that both genetic and environmental factors were needed for phenotype expression. We suspect that
rederivation into an SPF facility or altered exposure to pathogens or other unidentified substances modified environmental
interactions with the mutant allele, and so resulted in disappearance of the hyperresponsive phenotype. Our experience suggests
that future searches for genes that confer susceptibility for airway hyperresponsiveness might not be able to identify some
genes that confer susceptibility if the searches are performed in SPF facilities. Experimenters are advised to arrange for
multigeneration constancy of mouse care in order to clone mutant genes. Indeed, we were not able to map the mutation before
losing the phenotype. 相似文献
200.
Hynes J Wu H Pitt S Shen DR Zhang R Schieven GL Gillooly KM Shuster DJ Taylor TL Yang X McIntyre KW McKinnon M Zhang H Marathe PH Doweyko AM Kish K Kiefer SE Sack JS Newitt JA Barrish JC Dodd J Leftheris K 《Bioorganic & medicinal chemistry letters》2008,18(6):1762-1767
A novel structural class of p38alpha MAP kinase inhibitors has been identified via iterative SAR studies of a focused deck screen hit. Optimization of the lead series generated 6e, BMS-640994, a potent and selective p38alpha inhibitor that is orally efficacious in rodent models of acute and chronic inflammation. 相似文献