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991.
992.
The present study reports a previously undocumented mass spawning aggregation and group spawning phenomena of c. 1200 individual bumphead parrotfish Bolbometopon muricatum in Palau, Micronesia. Although B. muricatum are protected in Palau, it is further recommended that management strategies should consider establishment of no‐take zones at B. muricatum spawning aggregations and concomitant sleeping grounds elsewhere. 相似文献
993.
994.
目的 了解我国不同地区农村居民年度住院服务利用聚集性的现状及差异,分析可能影响其住院服务利用的因素。方法 采用分层整群随机抽样的方法,提取全国东中西6个县共12个乡镇居民新农合系统2014年的住院信息,运用Excel 2010编程技术进行合并,筛选等,获得患者年度的住院服务利用数据,并进行描述性分析。结果 农村居民年度住院1次的人数占比达70%;人均住院次数1.5~2次之间,住院服务利用的人数随着住院次数的增多逐渐减少;集中指数在0.2左右,其中互助集中指数最高为0.29,湟中最低为0.12;总体上平均25%的人群利用了45%左右的住院服务;女性的住院服务利用量均高于男性,46~60岁及60岁以上人群高住院利用较多,均占比20%左右。结论 不同地区农村居民年度住院服务利用总体分布一致;东中部服务利用聚集性普遍较高且内部差异不大,西部地区聚集性相对较低,但内部差异显著;女性住院服务利用率偏高,60岁以上人群偏好高住院利用。 相似文献
995.
目的 研究我国农村居民年度医疗服务利用聚集性。方法 收集我国东、中、西6个县域内的农村居民在县、乡、村三级医疗机构的就诊信息,运用Microsoft Excel编程技术,合并筛选居民个人年度的住院及门诊信息。分析我国农村居民的医疗服务利用聚集性程度及各个地区的水平差异。结果 农村居民年度医疗服务利用的人数及就诊单元量均随着就诊单元的增多逐渐减少;各个地区的平均就诊单元量介于5.22~12.17之间;集中指数均达到0.47以上,最高达0.62;总体上平均25%的人群利用了57.92%以上的医疗服务;高医疗服务利用人群以45~60岁较多。结论 不同地区农村居民年度医疗服务利用总体分布趋势基本一致;各个地区医疗服务利用均表现出较高的聚集性,且西部地区间的聚集性差异明显;性别年龄对医疗服务利用聚集性产生影响,高医疗服务利用以男性居多,45~60岁人群是高服务利用的主要人群。 相似文献
996.
Prion-like domains are low complexity, intrinsically disordered domains that compositionally resemble yeast prion domains. Many prion-like domains are involved in the formation of either functional or pathogenic protein aggregates. These aggregates range from highly dynamic liquid droplets to highly ordered detergent-insoluble amyloid-like aggregates. To better understand the amino acid sequence features that promote conversion to stable, detergent-insoluble aggregates, we used the prediction algorithm PAPA to identify predicted aggregation-prone prion-like domains with a range of compositions. While almost all of the predicted aggregation-prone domains formed foci when expressed in cells, the ability to form the detergent-insoluble aggregates was highly correlated with glutamine/asparagine (Q/N) content, suggesting that high Q/N content may specifically promote conversion to the amyloid state in vivo. We then used this data set to examine cross-seeding between prion-like proteins. The prion protein Sup35 requires the presence of a second prion, [PIN+], to efficiently form prions, but this requirement can be circumvented by the expression of various Q/N-rich protein fragments. Interestingly, almost all of the Q/N-rich domains that formed SDS-insoluble aggregates were able to promote prion formation by Sup35, highlighting the highly promiscuous nature of these interactions. 相似文献
997.
Chih-Kai Chang Steven S.-S. Wang Chun-Hsien Lo Hsiang-Chun Hsiao 《Journal of biomolecular structure & dynamics》2017,35(5):1042-1054
Cataract, a major cause of visual impairment worldwide, is a common disease of the eye lens related to protein aggregation. Several factors including the exposure of ultraviolet irradiation and possibly acidic condition may induce the unfolding and subsequent aggregation of the crystallin proteins leading to crystalline lens opacification. Human γD-crystallin (HγDC), a 173 residue monomeric protein, abundant in the nucleus of the human eye lens, has been shown to aggregate and form amyloid fibrils under acidic conditions and that this aggregation route is thought to be a potential initiation pathway for the onset of age-related nuclear cataract. However, the underlying mechanism of fibril formation remains elusive. This report is aimed at examining the structural changes and possible amyloid fibril formation pathway of HγDC using molecular dynamics and molecular docking simulations. Our findings demonstrated that incubation of HγDC under the acidic condition redistributes the protein surface charges and affects the protein interaction with its surrounding solvent environment. This brings about a twist motion in the overall tertiary structure that gives rise to newly formed anti-parallel β-strands in the C-terminal flexible loop regions. The change in protein structural conformation also involves an alteration in specific salt-bridge interactions. Altogether, these findings revealed a plausible mechanism for amyloid fibril formation of HγDC that is important to the early stages of HγDC aggregation involved in cataractogenesis. 相似文献
998.
Exploring the cause of aggregation and reduced Zn binding affinity by G85R mutation in SOD1 rendering amyotrophic lateral sclerosis
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Amyotrophic lateral sclerosis (ALS), a lethal neurodegenerative disorder is characterized by the degeneration of upper and lower motor neuron. ALS occurs due to various notably prominent missense mutations, in gene encoding Cu‐Zn superoxide dismutase (SOD1) thereby leading to aggregation, dysfunction and reduced Zn binding affinity. In this study, one such mutation, G85R was explored in comparison with wild type SOD1, using discrete molecular dynamics (DMD). Accordingly, the conformational changes were significantly observed in mutant SOD1, through various geometrical parameters, which substantiated the difference in conformational deviation, flexibility and compactness, thus stipulating a root cause for aggregation. Followed by, analysis of essential dynamics further authenticated the cause behind the protein dysfunction. In particular, the high content of beta sheet with structural deviations, down to dysfunction was established in mutant as compared to wild type, while passing through secondary structure analysis. Subsequently, the deviation of distance in Zn binding residues was distinctly portrayed in mutant as compared to wild type, thus confirming the cause of reduced Zn binding affinity. In addition, the steered molecular dynamics analysis also authenticated the above results indicating the reduced Zn binding affinity in the mutant as compared to that of the wild type. Hence, this work revealed the theoretical mechanism to unravel the mutational effects of cofactor dependent protein. Proteins 2017; 85:1276–1286. © 2017 Wiley Periodicals, Inc. 相似文献
999.
Wenqian Nong Anran Zhao Jinrui Wei Xiao Lin Lisheng Wang Cuiwu Lin 《Bioorganic & medicinal chemistry letters》2017,27(18):4506-4511
Ten new cinnamic acid derivatives containing a 2-aminothiazole substructure were designed and synthesized. This series of compounds exhibited good thermostabilities as demonstrated by thermogravimetric analysis. In coagulation assays (prothrombin time, activated partial thromboplastin time and thrombin time) in vitro, most compounds demonstrated excellent activities to promote blood coagulation. Among the studied series, compounds N1, N4, N5 and W5 exhibited a significant coagulation activity. Further studies indicated that compound N5 (IC50 = 1.87 μmol/L) displayed the most suitable efficacy of promoting platelet aggregation than the clinically used haemostatic drug etamsylate (IC50 = 46.22 μmol/L). Furthermore, the relationship between the functional groups of the compounds and the corresponding blood coagulant activity was explored in this study. 相似文献
1000.
Heparin‐induced amyloid fibrillation of β2‐microglobulin explained by solubility and a supersaturation‐dependent conformational phase diagram
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Masatomo So Yasuko Hata Hironobu Naiki Yuji Goto 《Protein science : a publication of the Protein Society》2017,26(5):1024-1036
Amyloid fibrils are fibrillar deposits of denatured proteins associated with amyloidosis and are formed by a nucleation and growth mechanism. We revisited an alternative and classical view of amyloid fibrillation: amyloid fibrils are crystal‐like precipitates of denatured proteins formed above solubility upon breaking supersaturation. Various additives accelerate and then inhibit amyloid fibrillation in a concentration‐dependent manner, suggesting that the combined effects of stabilizing and destabilizing forces affect fibrillation. Heparin, a glycosaminoglycan and anticoagulant, is an accelerator of fibrillation for various amyloidogenic proteins. By using β2‐microglobulin, a protein responsible for dialysis‐related amyloidosis, we herein examined the effects of various concentrations of heparin on fibrillation at pH 2. In contrast to previous studies that focused on accelerating effects, higher concentrations of heparin inhibited fibrillation, and this was accompanied by amorphous aggregation. The two‐step effects of acceleration and inhibition were similar to those observed for various salts. The results indicate that the anion effects caused by sulfate groups are one of the dominant factors influencing heparin‐dependent fibrillation, although the exact structures of fibrils and amorphous aggregates might differ between those formed by simple salts and matrix‐forming heparin. We propose that a conformational phase diagram, accommodating crystal‐like amyloid fibrils and glass‐like amorphous aggregates, is important for understanding the effects of various additives. 相似文献