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231.
When attempting to understand evolution, we traditionally rely on analysing evolutionary outcomes, despite the fact that unseen intermediates determine its course. A handful of recent studies has begun to explore these intermediate evolutionary forms, which can be reconstructed in the laboratory. With this first view on empirical evolutionary landscapes, we can now finally start asking why particular evolutionary paths are taken. 相似文献
232.
Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities 总被引:1,自引:0,他引:1
Stegmeier F Rape M Draviam VM Nalepa G Sowa ME Ang XL McDonald ER Li MZ Hannon GJ Sorger PK Kirschner MW Harper JW Elledge SJ 《Nature》2007,446(7138):876-881
The spindle checkpoint prevents chromosome mis-segregation by delaying sister chromatid separation until all chromosomes have achieved bipolar attachment to the mitotic spindle. Its operation is essential for accurate chromosome segregation, whereas its dysregulation can contribute to birth defects and tumorigenesis. The target of the spindle checkpoint is the anaphase-promoting complex (APC), a ubiquitin ligase that promotes sister chromatid separation and progression to anaphase. Using a short hairpin RNA screen targeting components of the ubiquitin-proteasome pathway in human cells, we identified the deubiquitinating enzyme USP44 (ubiquitin-specific protease 44) as a critical regulator of the spindle checkpoint. USP44 is not required for the initial recognition of unattached kinetochores and the subsequent recruitment of checkpoint components. Instead, it prevents the premature activation of the APC by stabilizing the APC-inhibitory Mad2-Cdc20 complex. USP44 deubiquitinates the APC coactivator Cdc20 both in vitro and in vivo, and thereby directly counteracts the APC-driven disassembly of Mad2-Cdc20 complexes (discussed in an accompanying paper). Our findings suggest that a dynamic balance of ubiquitination by the APC and deubiquitination by USP44 contributes to the generation of the switch-like transition controlling anaphase entry, analogous to the way that phosphorylation and dephosphorylation of Cdk1 by Wee1 and Cdc25 controls entry into mitosis. 相似文献
233.
Giridhar Pulletikurthi Bj?rn B?decker Andriy Borodin Bernd Weidenfeller Frank Endres 《自然科学进展(英文版)》2015,25(6):603-611
The addition of 1-butylpyrrolidine to AlCl_3 results in the formation of an electrolyte that is suited to Al deposition.The feasibility of electrodepositing Al from the synthesized electrolyte was investigated.Several compositions of AlCl_3 and 1-butylpyrrolidine were prepared for this purpose.These mixtures show a different phase behavior at various compositions of AlCl_3 and 1-butylpyrrolidine.IR,Raman and NMR spectroscopy were employed to characterize the synthesized liquids.Among the prepared compositions,1:1.2 mol ratio of 1-butylpyrrolidine:AlCl_3 and the upper phase of 1:1.3 mol ratio of 1-butylpyrrolidine:AlCl_3 were found to be suitable for Al electrodeposition at room temperature(RT).Uniform and thick( mm thick) layers of Al were obtained on copper at RT.Al deposition occured from the cationic species of AlCl_3 xLty(where x r 2,y ? 1–2,and L ? 1-butylpyrrolidine) in this electrolyte.This behavior is contrary to the well investigated classic AlCl_3 based ionic liquids,where the deposition of Al occurs mainly from anionic Al2 Cl 7ions. 相似文献
234.
235.
Hermann JC Marti-Arbona R Fedorov AA Fedorov E Almo SC Shoichet BK Raushel FM 《Nature》2007,448(7155):775-779
With many genomes sequenced, a pressing challenge in biology is predicting the function of the proteins that the genes encode. When proteins are unrelated to others of known activity, bioinformatics inference for function becomes problematic. It would thus be useful to interrogate protein structures for function directly. Here, we predict the function of an enzyme of unknown activity, Tm0936 from Thermotoga maritima, by docking high-energy intermediate forms of thousands of candidate metabolites. The docking hit list was dominated by adenine analogues, which appeared to undergo C6-deamination. Four of these, including 5-methylthioadenosine and S-adenosylhomocysteine (SAH), were tested as substrates, and three had substantial catalytic rate constants (10(5) M(-1 )s(-1)). The X-ray crystal structure of the complex between Tm0936 and the product resulting from the deamination of SAH, S-inosylhomocysteine, was determined, and it corresponded closely to the predicted structure. The deaminated products can be further metabolized by T. maritima in a previously uncharacterized SAH degradation pathway. Structure-based docking with high-energy forms of potential substrates may be a useful tool to annotate enzymes for function. 相似文献
236.
237.
利用毛细管辅助沉积方法制备了厚度及膜内裂缝的形状、分布可控的三维蛋白石薄膜。讨论了所得薄膜光学性质以及膜的形态特性与薄膜厚度之间的关系。用同样的方法制备了由不同粒径的球体基元晶体带构成的横向交替异质结构。 相似文献
238.
Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Reported as a new variety from the Green River Formation of Uintah and Duchesne counties, Utah, is Haplopappus armerioides (Nutt.) Gray var. gramineus Welsh & F. J. Smith. 相似文献
239.
Feng JQ Ward LM Liu S Lu Y Xie Y Yuan B Yu X Rauch F Davis SI Zhang S Rios H Drezner MK Quarles LD Bonewald LF White KE 《Nature genetics》2006,38(11):1310-1315
The osteocyte, a terminally differentiated cell comprising 90%-95% of all bone cells, may have multiple functions, including acting as a mechanosensor in bone (re)modeling. Dentin matrix protein 1 (encoded by DMP1) is highly expressed in osteocytes and, when deleted in mice, results in a hypomineralized bone phenotype. We investigated the potential for this gene not only to direct skeletal mineralization but also to regulate phosphate (P(i)) homeostasis. Both Dmp1-null mice and individuals with a newly identified disorder, autosomal recessive hypophosphatemic rickets, manifest rickets and osteomalacia with isolated renal phosphate-wasting associated with elevated fibroblast growth factor 23 (FGF23) levels and normocalciuria. Mutational analyses showed that autosomal recessive hypophosphatemic rickets family carried a mutation affecting the DMP1 start codon, and a second family carried a 7-bp deletion disrupting the highly conserved DMP1 C terminus. Mechanistic studies using Dmp1-null mice demonstrated that absence of DMP1 results in defective osteocyte maturation and increased FGF23 expression, leading to pathological changes in bone mineralization. Our findings suggest a bone-renal axis that is central to guiding proper mineral metabolism. 相似文献
240.
Taal HR St Pourcain B Thiering E Das S Mook-Kanamori DO Warrington NM Kaakinen M Kreiner-Møller E Bradfield JP Freathy RM Geller F Guxens M Cousminer DL Kerkhof M Timpson NJ Ikram MA Beilin LJ Bønnelykke K Buxton JL Charoen P Chawes BL Eriksson J Evans DM Hofman A Kemp JP Kim CE Klopp N Lahti J Lye SJ McMahon G Mentch FD Müller-Nurasyid M O'Reilly PF Prokopenko I Rivadeneira F Steegers EA Sunyer J Tiesler C Yaghootkar H;Cohorts for Heart Aging Research in Genetic Epidemiology Consortium 《Nature genetics》2012,44(5):532-538
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life. 相似文献