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排序方式: 共有608条查询结果,搜索用时 15 毫秒
581.
Joachim Berger Silke Berger Yu Shan G. Mok Mei Li Hakan Tarakci Peter D. Currie 《PLoS genetics》2022,18(2)
Myofibrils within skeletal muscle are composed of sarcomeres that generate force by contraction when their myosin-rich thick filaments slide past actin-based thin filaments. Although mutations in components of the sarcomere are a major cause of human disease, the highly complex process of sarcomere assembly is not fully understood. Current models of thin filament assembly highlight a central role for filament capping proteins, which can be divided into three protein families, each ascribed with separate roles in thin filament assembly. CapZ proteins have been shown to bind the Z-disc protein α-actinin to form an anchoring complex for thin filaments and actin polymerisation. Subsequent thin filaments extension dynamics are thought to be facilitated by Leiomodins (Lmods) and thin filament assembly is concluded by Tropomodulins (Tmods) that specifically cap the pointed end of thin filaments. To study thin filament assembly in vivo, single and compound loss-of-function zebrafish mutants within distinct classes of capping proteins were analysed. The generated lmod3- and capza1b-deficient zebrafish exhibited aspects of the pathology caused by variations in their human orthologs. Although loss of the analysed main capping proteins of the skeletal muscle, capza1b, capza1a, lmod3 and tmod4, resulted in sarcomere defects, residual organised sarcomeres were formed within the assessed mutants, indicating that these proteins are not essential for the initial myofibril assembly. Furthermore, detected similarity and location of myofibril defects, apparent at the peripheral ends of myofibres of both Lmod3- and CapZα-deficient mutants, suggest a function in longitudinal myofibril growth for both proteins, which is molecularly distinct to the function of Tmod4. 相似文献
582.
Mechanism of formation of 5-(hydroxymethyl)-2-furaldehyde from D-fructose an sucrose 总被引:1,自引:0,他引:1
The literature contains two alternative hypotheses for the mechanism of dehydration of fructose to 5-(hydroxymethyl)-2-furaldehyde (HMF), namely (1) a sequence of reactions commencing with and retaining the fructofuranose ring intact, and (2) a succession of reactions proceeding mainly via open-chain intermediates. The existing evidence for hypotheses (1) and (2) is reviewed and found to favor (1). The major products from fructose in water at 250 degrees, (with and without acid catalysis) have been investigated on a time-resolved basis and analysis of the results was found to confirm the first hypothesis. A necessary fructofuranosyl-cation intermediate in this hypothesis is produced directly by the hydrolysis of sucrose, and reacts to produce HMF in high yields. 相似文献
583.
Harmeet Singh Pamela Mok Thavamalar Balakrishnan Siti Norfiza Binte Rahmat Robert Zweigerdt 《Stem cell research》2010,4(3):165-179
We have systematically developed single cell-inoculated suspension cultures of human embryonic stem cells (hESC) in defined media. Cell survival was dependent on hESC re-aggregation. In the presence of the Rho kinase inhibitor Y-27632 (Ri) only ~ 44% of the seeded cells were rescued, but an optimized heat shock treatment combined with Ri significantly increased cell survival to ~ 60%. Mechanistically, our data suggest that E-cadherin plays a role in hESC aggregation and that dissociation and re-aggregation upon passaging functions as a purification step towards a pluripotency markers-enriched population. Mass expansion of hESC was readily achieved by up-scaling 2 ml cultures to serial passaging in 50 ml spinner flasks. A media comparison revealed that mTeSR was superior to KnockOut-SR in supporting cell proliferation and pluripotency. Persistent expression of pluripotency markers was achieved for two lines (hES2, hES3) that were used at higher passages (> 86). In contrast, rapid down regulation of Oct4, Tra-1-60, and SSEA4 was observed for ESI049, a clinically compliant line, used at passages 20-36. The up-scaling strategy has significant potential to provide pluripotent cells on a clinical scale. Nevertheless, our data also highlights a significant line-to-line variability and the need for a critical assessment of novel methods with numerous relevant cell lines. 相似文献
584.
M. Guo D. A. Lightfoot M. C. Mok D. W. S. Mok 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1991,81(5):703-709
Summary Restriction fragment length polymorphism (RFLP) was determined among P. vulgaris genotypes and Phaseolus species using 19 probes. The incidence of polymorphism was high (70–86%) between species, but relatively low (22–26%) between genotypes of P. vulgaris. Suitable probes were identified for the analysis of P. vulgaris and P. coccineus hybrids. The segregation pattern in F2 populations was Mendelian for two probes (LHB and VEE20) and non-Mendelian for GS-g, CHS, and CHI. Statistical analyses indicated gametic selection with preferential transmission of the P. vulgaris alleles, which may account for the selective recovery of P. vulgaris progeny types observed earlier. The available hybrids of P. vulgaris and P. coccineus and the high degree of interspecific RFLP will facilitate the construction of a linkage map for Phaseolus. 相似文献
585.
Jung Soh Paul MK Gordon Morgan L Taschuk Anguo Dong Andrew C Ah-Seng Andrei L Turinsky Christoph W Sensen 《BMC bioinformatics》2008,9(1):450
Background
The Bluejay genome browser has been developed over several years to address the challenges posed by the ever increasing number of data types as well as the increasing volume of data in genome research. Beginning with a browser capable of rendering views of XML-based genomic information and providing scalable vector graphics output, we have now completed version 1.0 of the system with many additional features. Our development efforts were guided by our observation that biologists who use both gene expression profiling and comparative genomics gain functional insights above and beyond those provided by traditional per-gene analyses. 相似文献586.
Christoph G.O. Baerwald C. C. Mok Mark S. Fife Mohammad Tikly Chak Sing Lau B. Paul Wordsworth Bill Ollier G.S. Panayi J.S. Lanchbury 《Immunogenetics》1999,49(10):894-899
The regulatory region of the corticotropin-releasing hormone (CRH) is highly conserved across species and plays a crucial
role in the response of the organism to stress. Release of CRH initiates a cascade of events leading to the release of cortisol
and the regulation of inflammatory and immune events. In this report we describe polymorphisms in the 5′ regulatory region
of the CRH gene in humans. We studied the distribution of CRH alleles in three different African populations, in white UK Caucasoids, and in a Chinese population. In the African and UK
populations we found three new polymorphisms which cosegregated, resulting in two alleles, A1 and A2. Gene frequencies for A1 and A2 were extremely divergent between the African and the UK populations. The African A1 frequency ranged from 0.27–0.3, while the UK Caucasoid frequency was 0.9. Compound alleles could be assigned by taking into
account the previously described biallelic polymorphism at position 225 in the CRH promoter. The A2B1 compound allele is the commonest in contemporary African human populations (allele frequency range 0.44–0.61) and was the
only allele observed in a population of chimpanzees from Sierra Leone. Wright's FST for the A2B1 allele over the four sampled populations was 0.612, a value exceeded in human populations only by loci which have apparently
been subject to natural selection. Taken together, these findings support A2B1 as the ancestral allele and suggest that the CRH genomic region may have been subject to strong disruptive selection throughout human evolution.
Received: 29 October 1998 / Revised: 24 March 1999 相似文献
587.
V A Hutchinson J L Angenend W L Mok J M Cummins A B Richards 《Molecular biotherapy》1990,2(3):160-164
Recombinant human interferon alfa-2a (HuIFN alpha) was administered orally once daily in a low concentration (1,200 IU/day) to nine patients with chronic recurrent aphthous stomatitis (RAS), and a placebo solution was given to 10 control chronic RAS patients in a double-blind study. All HuIFN alpha-treated patients had total remission of their aphthae within a 2-week period, while placebo control patients had no change in their condition. The 10 placebo control patients were then treated with HuIFN alpha in a manner identical to that used for the initial principal group. Within a 2-week period, all original placebo patients had complete remission of their aphthae. Eleven of the patients did not have a recurrence of RAS during a subsequent 6-month observation period. Eight patients had recurring aphthae; however, the lesions were resolved by retreating with oral HuIFN alpha for less than 1 week. 相似文献
588.
Gert Kreibich Maria Czak-Graham Ruth Grebenau Winnie Mok Enrique Rodriguez-Boulan David D. Sabatini 《Journal of cellular biochemistry》1978,8(3):279-302
Rat liver rough endoplasmic reticulum membranes (ER) contain two characteristic transmembrane glycoproteins which have been designated ribophorins I and II and are absent from smooth ER membranes. These proteins (MW 65,000 and 63,000 respectively) are related to the binding sites for ribosomes, as suggested by the following findings: (i) The ribophorin content of the rough ER membranes corresponds stoichiometrically to the number of bound ribosomes; (ii) ribophorins are quantitatively recovered with the bound polysomes after most other ER membrane proteins are dissolved with the nonionic detegent Kyro EOB; (iii) in intact rough microsomes ribophorins can be crosslinked chemically to the ribosomes and therefore are in close proximity to them. Treatment of rough microsomes with a low Triton X-100 concentration leads to the lateral displacement of ribosomes on the microsomal surface and to the formation of aggregates of bound ribosomes in areas of membranes which frequently invaginate into the microsomal lumen. Subfractionation of Triton-treated microsomes containing invaginations led to the recovery of smooth and “rough-inverted” vesicles. Ribophorins were present only in the latter fraction, indicating that both proteins are displaced together with the ribosome-binding capacity of rough and smooth microsomal membranes reconstituted after solubilization with detergents sugest that ribophorins are necessary for in vitro ribosome binding. Ribophorin-like proteins were found in rough microsomes obtained from secretory tissues of several animal species. The two proteins present in rat lacrimal gland microsomes have the same mobility as hepatocyte ribophorins and cross-react with antisera against them. 相似文献
589.
D. W. S. Mok M. C. Mok 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1977,49(3):145-149
Summary Two monosomics of Phaseolus vulgaris (2n = 22) were found among selfed progeny of plants treated with colchicine. The monosomic chromosomes involved were identified as chromosomes H and J according to the previously suggested Giemsa karyotype. Both monosomic plants had slower growth rate and smaller size as compared with their respective euploid sibs. However, no apparent morphological characteristics distinguished the two monosomics. The frequencies of transmission through selfing of monosomics H and J were 9% and 10 % respectively. 相似文献
590.
Christopher J. Handley Meng Tuck Mok Mirna Z. Ilic Clair Adcocks David J. Buttle H. Clem Robinson 《Matrix biology》2001,20(8):531-553
Bovine aggrecan was digested with bovine cathepsin D at pH 5.2 under conditions of partial digestion and the resulting aggrecan core protein fragments were separated by electrophoresis on gradient polyacrylamide gels. The fragments were characterized by their reactivity to specific antibodies and by N-terminal amino acid sequencing. It was also demonstrated that cathepsin D cleaved bovine aggrecan at five sites within the core protein, between residues Phe(342)-Phe(343) in the interglobular domain, Leu(1462)-Val(1463) between the chondroitin sulfate attachment regions 1 and 2 and Leu(1654)-Val(1655), Phe(1754)-Val(1755) and Leu(1854)-Ile(1855) that are located within the chondroitin sulfate attachment region 2 of the core protein. The time course of digestion showed that there was a continued degradation of aggrecan and there was no preferential cleavage of the core protein at any one site. It was shown that cathepsin D digested aggrecan over the pH range 5.2-6.5 resulting in the same products. When bovine cartilage was maintained in explant culture at pH 5.2 there was a rapid loss of both radiolabeled and chemical pools of sulfated glycosaminoglycans into the culture medium and this loss was inhibited by the inclusion in the medium of the aspartic proteinase inhibitor, pepstatin A. The aggrecan core protein fragments appearing in the medium of cultures maintained at pH 5.2 were characterized and it was shown that the fragments had N-terminal sequences starting at Phe(343), Ile(1855), and Val(1755) or Val(1463). This work demonstrates that cathepsin D present within the extracellular matrix of articular cartilage has the potential to contribute to the proteolytic processing of the core protein of aggrecan in this tissue. 相似文献