USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM

The human RecQ helicase BLM is involved in the DNA damage response, DNA metabolism, and genetic stability. Loss of function mutations in BLM cause the genetic instability/cancer predisposition syndrome Bloom syndrome. However, the molecular mechanism underlying the regulation of BLM in cancers remains largely elusive. Here, we demonstrate that the deubiquitinating enzyme USP37 interacts with BLM and that USP37 deubiquitinates and stabilizes BLM, thereby sustaining the DNA damage response (DDR). Mechanistically, DNA double-strand breaks (DSB) promotes ATM phosphorylation of USP37 and enhances the binding between USP37 and BLM. Moreover, knockdown of USP37 increases BLM polyubiquitination, accelerates its proteolysis, and impairs its function in DNA damage response. This leads to enhanced DNA damage and sensitizes breast cancer cells to DNA-damaging agents in both cell culture and in vivo mouse models. Collectively, our results establish a novel molecular mechanism for the USP37–BLM axis in regulating DSB repair with an important role in chemotherapy and radiotherapy response in human cancers.     

鱼类趋化因子的研究进展

趋化因子(Chemokine)是由多种细胞在致病因子刺激后分泌的一类低分子量的细胞因子,它们都具有激活和趋化白细胞的作用。趋化因子从结构上可分为四类:CC型、CXC型、CX3C型和C型;从功能上可分为两种类型:一类主要诱导白细胞到炎症部位;另一类主要是对肌体起免疫监控作用。目前,有关鱼类趋化因子的研究主要集中于CXC型和CC型两类,以及其在非特异性免疫中的作用。     

Haemagglutinating activity of Campylobacter pylori

Abstract Thirty-one isolates of Campylobacter pylori , screened for their ability to agglutinate a panel of erythrocyte species, could be divided into two phenotypic groups on the basis of their ability to agglutinate human A and O erythrocytes, a property which correlated strongly with their ability to agglutinate horse and cat erythrocytes. Isolates which agglutinated human red blood cells exhibited a broad-spectrum haemagglutination profile on other red blood cells including dog, goat, guinea-pig, ox, rat and sheep erythrocytes. Agglutination dog, guinea-pig, horse and human erythrocytes by C. pylori was mannose-resistant. Haemagglutination was not inhibited by other saccharides tested nor by two glycoproteins or serine. The bacterial ligand was protease- and heat-sensitive. Neither protease nor neuraminidase treatment of erythrocytes prevented agglutination.     

商业界参与生物多样性主流化的进展、路径与建议

商业界在生物多样性主流化进程中发挥重要作用。本文概述了商业界对生物多样性的依赖和影响, 回顾了《生物多样性公约》与商业界有关的生物多样性主流化决定。对《2011-2020生物多样性战略计划》中4个主流化目标执行进展的分析表明, 加强商业界参与是对未来生物多样性行动提出更高要求的先决条件之一。文章梳理了4条加强商业界参与的全球路径, 包括提高认识, 引导资金流向, 完善报告体系和建立合作伙伴关系; 归纳出缺乏价值认知, 融资存在挑战, 需要更多技术方法支持和需要能力建设4个挑战。最后提出了促进商业界参与生物多样性主流化进程的建议, 包括加强生物多样性融资, 完善环境绩效体系, 加强科学支撑和建立多方协作机制。     

Systematic Review of Clinical Practice Guidelines Related to Multiple Sclerosis

Background

High quality clinical practice guidelines (CPGs) can provide clinicians with explicit recommendations on how to manage health conditions and bridge the gap between research and clinical practice. Unfortunately, the quality of CPGs for multiple sclerosis (MS) has not been evaluated.

Objective

To evaluate the methodological quality of CPGs on MS using the AGREE II instrument.

Methods

According to the inclusion and exclusion criteria, we searched four databases and two websites related to CPGs, including the Cochrane library, PubMed, EMBASE, DynaMed, the National Guideline Clearinghouse (NGC), and Chinese Biomedical Literature database (CBM). The searches were performed on September 20th 2013. All CPGs on MS were evaluated by the AGREE II instrument. The software used for analysis was SPSS 17.0.

Results

A total of 27 CPGs on MS met inclusion criteria. The overall agreement among reviews was good or substantial (ICC was above 0.70). The mean scores for each of all six domains were presented as follows: scope and purpose (mean ± SD: 59.05±16.13), stakeholder involvement (mean ± SD: 29.53±17.67), rigor of development (mean ± SD: 31.52±21.50), clarity of presentation (mean ± SD: 60.39±13.73), applicability (mean ± SD: 27.08±17.66), editorial independence (mean ± SD: 28.70±22.03).

Conclusions

The methodological quality of CPGs for MS was acceptable for scope, purpose and clarity of presentation. The developers of CPGs need to pay more attention to editorial independence, applicability, rigor of development and stakeholder involvement during the development process. The AGREE II instrument should be adopted by guideline developers.     

生态系统服务研究在生态红线政策保护成效评估中的应用

生态保护红线政策是中国推进生态保护与建设的宏观政策,其保护成效评估是国内外关注的重大科学问题。在分析国内外生态系统服务研究进展及中国生态保护红线内涵、划定进程及管控要求的基础上,结合生态红线政策与生态系统服务研究的关联及生态系统服务研究在红线政策保护成效评估应用中面临的挑战,提出了红线政策实施效果评估的技术框架和基本思路。开展生态红线政策保护成效评估,能从科学上明确生态红线政策实施对多尺度利益相关者成本、效益的影响,为生态红线政策的综合研究提供框架和科学方法;从政策设计上,为生态红线布局进一步优化提供依据;从制度建设上,提出符合生态红线政策实施的制度框架,推动生态保护红线制度建设由理论走向实践。     

Comparison of microRNAs in the intramuscular adipose tissue from Jinhua and Landrace pigs

MicroRNA (miRNA) is critically involved in lipogenesis occurring in various body parts of humans and animals. In this study, to further investigate the role and distribution of miRNA in porcine intramuscular adipose tissue, small RNAs were extracted from Jinhua and Landrace pigs to identify the expression profiles of miRNAs. miRNA expression profiles revealed that 558 miRNAs including 287 known and 271 novel miRNAs were identified, and 220 of them showed differential expression in the pigs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis suggested that the target genes of the differentially expressed miRNAs were involved in fatty metabolism. In conclusion, the current study reveals the active participation of miRNAs in the regulation of adipogenesis in the intramuscular adipose tissue of Jinhua and Landrace pigs.     

一种来自乳酸乳球菌的新型氨肽酶A的制备及特性分析

氨肽酶A(aminopeptidase A,Pep A)能特异性地水解N末端为谷氨酸(glutamic acid,Glu)或天冬氨酸(asparticacid,Asp)的肽链,提高蛋白质的水溶性和食物的风味,在食品工业和肉类加工中具有一定的应用前景。本研究采用全基因合成的方式获得了乳酸乳球菌(Lactococcus lactis ssp.lactis)IL1403氨肽酶A(Lactococcus lactis-Pep A,Lc-Pep A)的编码基因,将该基因克隆并导入毕赤酵母(Pichia pastoris)GS115(His4),在毕赤酵母中实现了Lc-Pep A的高效分泌表达,表达产物经鉴定和纯化制备后,进行了生物学特性的分析。结果表明,Lc-Pep A具有较强的底物特异性,对2种底物谷氨酸对硝基苯胺(glutamicacid-p-nitroaniline,Glu-pNA)和天冬氨酸对硝基苯胺(aspartic acid-p-nitroaniline,Asp-pNA)具有相似的催化活力和酶动力学参数。Lc-Pep A是一种金属蛋白酶,最适反应温度为60℃,最适pH为8.0,具有较宽的热稳定性和酸碱稳定性。金属离子Co^(2+)、Mn^(2+)及Zn^(2+)等对酶活力具有不同程度的激活作用,而Ni^(2+)和Cu^(2+)对酶活力具有强烈的抑制作用。Lc-Pep A对常规蛋白酶抑制剂不敏感,但能被金属蛋白酶抑制剂、EDTA及二硫键还原剂抑制。这些研究为Lc-Pep A的生产和指导该酶的应用打下了坚实的基础。     

Variations in the nitrogen saturation threshold of soil respiration in grassland ecosystems

Over the last century, anthropogenic activities have increased nitrogen (N) deposition considerably, which significantly affects ecosystem processes and has the potential to induce N saturation in the future. The continuous increase in N deposition may cause a non-linear response in soil respiration (Rs), an important component of carbon (C) cycling. However, little is known about N saturation threshold of soil respiration. In this study, we conducted coordinated experiments in four grassland types across northern China with four N addition levels to explore patterns in the Rs saturation threshold. Our results showed that an Rs saturation threshold generally exists in grassland ecosystems in response to N addition gradients. The N saturation threshold of Rs occurred at an average rate of 50 kg N ha⁻¹ yr⁻¹, but varied widely with grassland type; the N saturation threshold occurred at rates of 100, 50, 50, and 25 kg N ha⁻¹ yr⁻¹ in the alpine meadow, meadow steppe, typical steppe, and desert steppe, respectively. Autotrophic respiration (Ra) and heterotrophic respiration (Rh) responded to N addition gradients differently. Ra increased initially and became saturated at a rate of 50 kg N ha⁻¹ yr⁻¹ and declined thereafter. In contrast, Rh decreased monotonically after N addition. Structural equation models further confirmed that the effects of N addition gradients on Rs were primarily determined by the non-linear response of belowground biomass. Interestingly, the compiled global dataset showed that the N saturation threshold of Rs increased with precipitation and soil moisture. These findings indicate that the stimulating effect of N deposition on Rs and Ra might diminish with increasing N deposition in the future, especially in dry grassland ecosystems.