Post-translational Modification in Control of SIRT1 Stability during DNA Damage Response

SIRT1 (silent mating type information regulation 2 homolog 1), a class III histone deacetylase, is known to participate in multiple steps of the DNA damage response (DDR) by deacetylating several key DDR proteins. At present, the mechanisms regulating SIRT1 protein stability upon DNA damage have yet to be fully elucidated. In this study, we reveal that, under severe DNA damage, SIRT1 undergoes two forms of post-translational modifications (PTMs): (i) increased polyubiquitination and proteasomal degradation mediated by TRIM28 (tripartite motif-containing protein 28), a RING-domain E3 ligase; and (ii) cleavage at C-terminal mediated by caspases. Importantly, there is reciprocal effects between these forms of PTMs: while suppression of proteasome reduces caspases-mediated cleavage, the cleaved SIRT1 has enhanced interaction with TRIM28, thus facilitating the ubiquitination and proteasomal degradation of SIRT1. Functionally, SIRT1 works as an anti-apoptotic protein in DDR, and the above-mentioned PTMs of SIRT1 subsequently enhances cell death induced by DNA damage agents. Thus, our study has uncovered a pivotal role of SIRT1 post-translational regulation in determining cell fate in DDR.     

Seasonal and spatial variability of zooplankton diversity in the Poyang Lake Basin using DNA metabarcoding

Freshwater ecosystems face multiple threats to their stability globally. Poyang Lake is the largest lake in China, but its habitat has been seriously degraded because of human activities and natural factors (e.g. climate change), resulting in a decline in freshwater biodiversity. Zooplankton are useful indicators of environmental stressors because they are sensitive to external perturbations. DNA metabarcoding is an approach that has gained significant traction by aiding ecosystem conservation and management. Here, the seasonal and spatial variability in the zooplankton diversity were analyzed in the Poyang Lake Basin using DNA metabarcoding. The results showed that the community structure of zooplankton exhibited significant seasonal and spatial variability using DNA metabarcoding, where the community structure was correlated with turbidity, water temperature, pH, total phosphorus, and chlorophyll‐a. These results indicated habitat variations affected by human activities and seasonal change could be the main driving factors for the variations of zooplankton community. This study also provides an important reference for the management of aquatic ecosystem health and conservation of aquatic biodiversity.     

一种基于SWAT模型的干旱牧区生态脆弱性评价方法——以艾布盖河流域为例

针对干旱牧区生态脆弱性特点,以GIS为平台,利用气象、土壤、土地利用、水资源开发利用等数据,结合SWAT模型模拟结果,建立了一种基于SWAT模型子流域划分的干旱牧区生态脆弱性评价体系,对西北干旱牧区艾布盖河流域1990年、2010年生态脆弱性进行了评价。从评价结果可以看出,研究区北部及西部生态稳定性保持较好,生态脆弱等级下降主要发生在研究区的东南部,20年间耕地扩张造成的草地被侵占及水资源过度开发利用是造成生态退化的主要原因。评价体系紧紧围绕干旱牧区"水-草-畜"关系设置评价指标,将观测数据与水文模型模拟相结合,统计数据与空间地类相联系,点面结合,能够较好的反映出研究区20年间生态脆弱程度变化趋势及主要问题。     

Is negative density‐dependent reproduction regulated by density‐induced stress in root voles? Two field experiments

Density dependence in reproduction plays an important role in stabilizing population dynamics via immediate negative feedback from population density to reproductive output. Although previous studies have shown that negative density‐dependent reproduction is associated with strong spacing behavior and social interaction between individuals, the proximal mechanism for generating negative density‐dependent reproduction remains unclear. In this study, we investigated the effects of density‐induced stress on reproduction in root voles. Enclosed founder populations were established by introducing 6 (low density) and 30 (high density) adults per sex into per enclosure (four enclosures per density in total) during the breeding season from April to July 2012 and from May to August 2015. Fecal corticosterone metabolite (FCM) levels, reproductive traits (recruitment rate and the proportion of reproductively active individuals), and founder population numbers were measured following repeated live trapping in both years. The number of founders was negatively associated with recruitment rates and the proportion of reproductively active individuals, displaying a negative density‐dependent reproduction. FCM level was positively associated with the number of founders. The number of founder females directly affected the proportion of reproductive females, and directly and indirectly through their FCM levels affected the recruitment rate; the effect of the number of male founders on the proportion of reproductive males was mediated by their FCM level. Our results showed that density‐induced stress negatively affected reproductive traits and that density‐induced stress is one ecological factor generating negative density‐dependent reproduction.     

miR-140-3p suppresses the proliferation and migration of macrophages

Macrophages benefit myelin debris removal, blood vessel formation, and Schwann cell activation following peripheral nerve injury. Identifying factors that modulate macrophage phenotype may advantage the repair and regeneration of injured peripheral nerves. microRNAs (miRNAs) are important regulators of many physiological and pathological processes, including peripheral nerve regeneration. Herein, we investigated the regulatory roles of miR-140-3p, a miRNA that was differentially expressed in injured rat sciatic nerves, in macrophage RAW264.7 cells. Observations from EdU proliferation assay demonstrated that elevated miR-140-3p decreased the proliferation rates of RAW264.7 cells while suppressed miR-140-3p increased the proliferation rates of RAW264.7 cells. Transwell-based migration assay showed that up-regulated and down-regulated miR-140-3p led to elevated and reduced migration abilities, respectively. However, the abundances of numerous phenotypic markers of M1 and M2 macrophages were not significantly altered by miR-140-3p mimic or inhibitor transfection. Bioinformatic analysis and miR-140-3p-induced gene suppression examination suggested that Smad3 might be the target gene of miR-140-3p. These findings illuminate the inhibitory effects of miR-140-3p on the proliferation and migration of macrophages and contribute to the cognition of the essential roles of miRNAs during peripheral nerve regeneration.     

全耐药鲍曼不动杆菌分子分型和分子流行病学调查

重复片段引物PCR和随机扩增多态性DNA(RAPD)技术对临床分离全耐药不动杆菌分子分型,并进行流行病学调查.从ICU病房感染多重耐药不动杆菌患者的标本分离不动杆菌,碱裂解法提取全基因组,重复片段引物PCR(Rep-PCR)和随机引物扩增(RAPD),对8株临床分离的全耐药菌基因分型,并与生物学分型和质粒分型比较,调查医院流行全耐药菌的基因型.结果显示,8株分离菌经两对重复片段引物分型可分为6种和4种基因型,经随机引物分型为4种和3种基因型,经质粒分型可分为2种基因型,生物学分型归属为1种表型.PCR方法用于全耐药不动杆菌分子分型简便易行,重复性好,适合医院感染流行病学调查,本医院同一部门出现多种基因型,各科室间不存在交叉传染.     

Human glutathione S-transferase P1 suppresses MEKK1-mediated apoptosis by regulating MEKK1 kinase activity in HEK293 cells

Glutathione S-transferase P1 (GSTP1) plays an important role in detoxification and the metabolism of xenobiotics. Here we show that GSTP1 also regulates the MEKK1-MKK7 signaling pathway. Over-expression of GSTP1 in HEK293 cells inhibited both DMEKK1- and etoposide-induced apoptosis, and inhibited pro-caspase-3 activation and PARP cleavage. MEKK1-induced apoptosis requires both its kinase activity and proteolytic cleavage. DMEKK1 activity was inhibited by over-expression of GSTP1 in vivo and MEKK1 kinase activity was also inhibited by GSTP1 in vitro when assayed with bacterially-expressed MKK7(KM) protein as substrate. GSTP1 inhibition of etoposide-induced cell apoptosis was mainly due to its ability to suppress MEKK1 kinase activity. The glutathione-conjugating activity of GSTP1 was essential for the above effects. These findings provide insight into the mechanism by which GSTP1 protects cells from genotoxin-induced apoptosis.     

AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia/reperfusion

We recently reported that the expression of the synaptic form of acetylcholinesterase (AChE) is induced during apoptosis in various cell types in vitro. Here, we provide evidence to confirm that AChE is expressed during ischemia–reperfusion (I/R)-induced apoptosis in vivo. Renal I/R is a major cause of acute renal failure (ARF), resulting in injury and the eventual death of renal cells due to a combination of apoptosis and necrosis. Using AChE-deficient mice and AChE inhibitors, we investigated whether AChE deficiency or inhibition can protect against apoptosis caused by I/R in a murine kidney model. Unilateral clamping of renal pedicles for 90 min followed by reperfusion for 24 h caused significant renal dysfunction and injury. Both genetic AChE deficiency and chemical inhibition of AChE (provided by huperzine A, tacrine and donepezil) significantly reduced the biochemical and histological evidence of renal dysfunction following I/R. Activation of caspases-8, -9, -12, and -3 in vivo were prevented and associated with reduced levels of cell apoptosis and cell death. A further investigation also confirmed that AChE deficiency down-regulated p53 induction and phosphorylation at serine-15, and decreased the Bax/Bcl-2 ratio during I/R. In conclusion, our study demonstrates that AChE may be a pro-apoptotic factor and the inhibition of AChE reduces renal I/R injury. These findings suggest that AChE inhibitors may represent a therapeutic strategy for protection against ischemic acute renal failure.