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排序方式: 共有368条查询结果,搜索用时 15 毫秒
81.
82.
Protein engineering of the colony-stimulating factor-1 receptor kinase domain for structural studies
Schalk-Hihi C Ma HC Struble GT Bayoumy S Williams R Devine E Petrounia IP Mezzasalma T Zeng L Schubert C Grasberger B Springer BA Deckman IC 《The Journal of biological chemistry》2007,282(6):4085-4093
A parallel approach to designing crystallization constructs for the c-FMS kinase domain was implemented, resulting in proteins suitable for structural studies. Sequence alignment and limited proteolysis were used to identify and eliminate unstructured and surface-exposed domains. A small library of chimeras was prepared in which the kinase insert domain of FMS was replaced with the kinase insert domain of previously crystallized receptor-tyrosine kinases. Characterization of the newly generated FMS constructs by enzymology and thermoshift assays demonstrated similar activities and compound binding to the FMS full-length cytoplasmic domain. Two chimeras were evaluated for crystallization in the presence and absence of a variety of ligands resulting in crystal structures, and leading to a successful structure-based drug design project for this important inflammation target. 相似文献
83.
Qi J Lang W Geisler JG Wang P Petrounia I Mai S Smith C Askari H Struble GT Williams R Bhanot S Monia BP Bayoumy S Grant E Caldwell GW Todd MJ Liang Y Gaul MD Demarest KT Connelly MA 《Journal of lipid research》2012,53(6):1106-1116
Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride (TG) synthesis. There are two isoforms, DGAT1 and DGAT2, with distinct protein sequences and potentially different physiological functions. To date, the ability to determine clear functional differences between DGAT1 and DGAT2, especially with respect to hepatic TG synthesis, has been elusive. To dissect the roles of these two key enzymes, we pretreated HepG2 hepatoma cells with (13)C(3)-D(5)-glycerol or (13)C(18)-oleic acid, and profiled the major isotope-labeled TG species by liquid chromatography tandem mass spectrometry. Selective DGAT1 and DGAT2 inhibitors demonstrated that (13)C(3)-D(5)-glycerol-incorporated TG synthesis was mediated by DGAT2, not DGAT1. Conversely, (13)C(18)-oleoyl-incorporated TG synthesis was predominantly mediated by DGAT1. To trace hepatic TG synthesis and VLDL triglyceride (VLDL-TG) secretion in vivo, we administered D(5)-glycerol to mice and measured plasma levels of D(5)-glycerol-incorporated TG. Treatment with an antisense oligonucleotide (ASO) to DGAT2 led to a significant reduction in D(5)-glycerol incorporation into VLDL-TG. In contrast, the DGAT2 ASO had no effect on the incorporation of exogenously administered (13)C(18)-oleic acid into VLDL-TG. Thus, our results indicate that DGAT1 and DGAT2 mediate distinct hepatic functions: DGAT2 is primarily responsible for incorporating endogenously synthesized FAs into TG, whereas DGAT1 plays a greater role in esterifying exogenous FAs to glycerol. 相似文献
84.
85.
Marinou I Montgomery DS Dickson MC Binks MH Moore DJ Bax DE Wilson AG 《Arthritis research & therapy》2007,9(2):R40
An important feature of autoimmune diseases is the overlap of pathophysiological characteristics. Clustering of autoimmune
diseases in families suggests that genetic variants may contribute to autoimmunity. The aim of the present study was to investigate
the role of the interferon induced with helicase domain 1 (IFIH1) A946T (rs1990760 A>G) variant in rheumatoid arthritis (RA),
as this was recently associated with susceptibility to type 1 diabetes. A total of 965 Caucasians with RA and 988 healthy
controls were genotyped for IFIH1 A946T. Gene expression of IFIH1 was measured in peripheral blood leukocytes using real-time
PCR. Genotypes were equally distributed in both RA cases and healthy controls (odds ratio for allele C = 0.9, 95% confidence
interval = 0.8–1.0, P = 0.3). No association was detected after stratification by sex, age at onset, rheumatoid factor status, anti-cyclic citrullinated
peptide status or radiological joint damage. Levels of IFIH1 mRNA were approximately twofold higher in blood leucocytes of
RA cases compared with healthy controls (P < 0.0001). These results indicate that the IFIH1 is upregulated in RA but that the A946T variant does not contribute significantly
to the genetic background of RA. 相似文献
86.
M Huntemann H Teshima A Lapidus M Nolan S Lucas N Hammon S Deshpande JF Cheng R Tapia LA Goodwin S Pitluck K Liolios I Pagani N Ivanova K Mavromatis N Mikhailova A Pati A Chen K Palaniappan M Land L Hauser C Pan EM Brambilla M Rohde S Spring M Göker JC Detter J Bristow JA Eisen V Markowitz P Hugenholtz NC Kyrpides HP Klenk T Woyke 《Standards in genomic sciences》2012,6(2):185-193
Muricauda ruestringensis Bruns et al. 2001 is the type species of the genus Muricauda, which belongs to the family Flavobacteriaceae in the phylum Bacteroidetes. The species is of interest because of its isolated position in the genomically unexplored genus Muricauda, which is located in a part of the tree of life containing not many organisms with sequenced genomes. The genome, which consists of a circular chromosome of 3,842,422 bp length with a total of 3,478 protein-coding and 47 RNA genes, is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
87.
88.
Johnson T Gaunt TR Newhouse SJ Padmanabhan S Tomaszewski M Kumari M Morris RW Tzoulaki I O'Brien ET Poulter NR Sever P Shields DC Thom S Wannamethee SG Whincup PH Brown MJ Connell JM Dobson RJ Howard PJ Mein CA Onipinla A Shaw-Hawkins S Zhang Y Davey Smith G Day IN Lawlor DA Goodall AH;Cardiogenics Consortium Fowkes FG Abecasis GR Elliott P Gateva V;Global BPgen Consortium Braund PS Burton PR Nelson CP Tobin MD van der Harst P Glorioso N Neuvrith H Salvi E Staessen JA Stucchi A Devos N 《American journal of human genetics》2011,(6):688-700
89.
Cipriani S Bonini D Marchina E Balgkouranidou I Caimi L Grassi Zucconi G Barlati S 《Cell biology international》2007,31(8):845-850
Amniotic fluid has been recently suggested as an alternative source of mesenchymal stem cells. However, the fate of amniotic fluid-derived mesenchymal stem cells (AF-MSCs) after in vivo transplantation has yet to be determined. In the present study we explored whether human AF-MSCs could survive and migrate following transplantation into the striatum of normal and ischemic rat. We found that the grafted cells could survive and migrate towards multiple brain regions in the normal animals, while they moved towards the injured region in the ischemic rat. Double-immunostaining analyses showed that the implanted human AF-MSCs express markers for immature neurons (Doublecortin) at 10 days, and for astrocytes (GFAP) at 10, 30 and 90 after transplantation. This study provides the first evidence that human amniotic fluid contains cells having the potential to survive and integrate into adult rat brain tissue and, therefore, to function as effective stem cells for therapeutic strategies. 相似文献
90.
Maria Koufaki Theano Fotopoulou Efstathios K. Iliodromitis Sophia-Iris Bibli Anastasia Zoga Dimitrios Th. Kremastinos Ioanna Andreadou 《Bioorganic & medicinal chemistry》2012,20(19):5948-5956
Novel purine analogues bearing nitrate esters were designed and synthesized in an effort to develop compounds triggering endogenous cardioprotective mechanisms such as ischemic preconditioning (IPC) or postconditioning (PostC). The majority of the compounds reduced infarct size compared to the control group in anesthetized rabbits, whereas administration of the most active analogue 16 at a dose of 3.8 μmol/kg resulted on a significant reduction of infarct size, compared to PostC group (13.4 ± 1.9% vs 26.4 ± 2.3%). These findings introduce a novel class of promising pharmacological compounds that could be used as mimics or enhancers of PostC. 相似文献