IOP1 Protein Is an External Component of the Human Cytosolic Iron-Sulfur Cluster Assembly (CIA) Machinery and Functions in the MMS19 Protein-dependent CIA Pathway

The emerging link between iron metabolism and genome integrity is increasingly clear. Recent studies have revealed that MMS19 and cytosolic iron-sulfur cluster assembly (CIA) factors form a complex and have central roles in CIA pathway. However, the composition of the CIA complex, particularly the involvement of the Fe-S protein IOP1, is still unclear. The roles of each component are also largely unknown. Here, we show that MMS19, MIP18, and CIAO1 form a tight “core” complex and that IOP1 is an “external” component of this complex. Although IOP1 and the core complex form a complex both in vivo and in vitro, IOP1 behaves differently in vivo. A deficiency in any core component leads to down-regulation of all of the components. In contrast, IOP1 knockdown does not affect the level of any core component. In MMS19-overproducing cells, other core components are also up-regulated, but the protein level of IOP1 remains unchanged. IOP1 behaves like a target protein in the CIA reaction, like other Fe-S helicases, and the core complex may participate in the maturation process of IOP1. Alternatively, the core complex may catch and hold IOP1 when it becomes mature to prevent its degradation. In any case, IOP1 functions in the MMS19-dependent CIA pathway. We also reveal that MMS19 interacts with target proteins. MIP18 has a role to bridge MMS19 and CIAO1. CIAO1 also binds IOP1. Based on our in vivo and in vitro data, new models of the CIA machinery are proposed.     

Akt Activation Emulates Chk1 Inhibition and Bcl2 Overexpression and Abrogates G2 Cell Cycle Checkpoint by Inhibiting BRCA1 Foci

Akt is perhaps the most frequently activated oncoprotein in human cancers. Overriding cell cycle checkpoint in combination with the inhibition of apoptosis are two principal requirements for predisposition to cancer. Here we show that the activation of Akt is sufficient to promote these two principal processes, by inhibiting Chk1 activation with concomitant inhibition of apoptosis. These activities of Akt cannot be recapitulated by the knockdown of Chk1 alone or by overexpression of Bcl2. Rather the combination of Chk1 knockdown and Bcl2 overexpression is required to recapitulate Akt activities. Akt was shown to directly phosphorylate Chk1. However, we found that Chk1 mutants in the Akt phosphorylation sites behave like wild-type Chk1 in mediating G2 arrest, suggesting that the phosphorylation of Chk1 by Akt is either dispensable for Chk1 activity or insufficient by itself to exert an effect on Chk1 activity. Here we report a new mechanism by which Akt affects G2 cell cycle arrest. We show that Akt inhibits BRCA1 function that induces G2 cell cycle arrest. Akt prevents the translocation of BRCA1 to DNA damage foci and, thereby, inhibiting the activation of Chk1 following DNA damage.     

Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats

Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney.     

Human Pluripotent Stem Cells Have a Novel Mismatch Repair-dependent Damage Response

Human pluripotent stem cells (PSCs) are presumed to have robust DNA repair pathways to ensure genome stability. PSCs likely need to protect against mutations that would otherwise be propagated throughout all tissues of the developing embryo. How these cells respond to genotoxic stress has only recently begun to be investigated. Although PSCs appear to respond to certain forms of damage more efficiently than somatic cells, some DNA damage response pathways such as the replication stress response may be lacking. Not all DNA repair pathways, including the DNA mismatch repair (MMR) pathway, have been well characterized in PSCs to date. MMR maintains genomic stability by repairing DNA polymerase errors. MMR is also involved in the induction of cell cycle arrest and apoptosis in response to certain exogenous DNA-damaging agents. Here, we examined MMR function in PSCs. We have demonstrated that PSCs contain a robust MMR pathway and are highly sensitive to DNA alkylation damage in an MMR-dependent manner. Interestingly, the nature of this alkylation response differs from that previously reported in somatic cell types. In somatic cells, a permanent G₂/M cell cycle arrest is induced in the second cell cycle after DNA damage. The PSCs, however, directly undergo apoptosis in the first cell cycle. This response reveals that PSCs rely on apoptotic cell death as an important defense to avoid mutation accumulation. Our results also suggest an alternative molecular mechanism by which the MMR pathway can induce a response to DNA damage that may have implications for tumorigenesis.     

基于耦合协调度的黄土高原地区NDVI与降水关系的变异诊断

植被是地表生态系统的重要"指示器"，在能量交换、水循环、碳循环、生物地球化学循环和维持中发挥着重要作用，降水是影响植被变化的主要气候因子，研究两者之间的作用关系具有重要的意义和价值。利用Mann-Kendall趋势检验法和Hust指数分析了黄土高原地区归一化植被指数（NDVI）的变化趋势，使用相对发展率（RDR）指数和重心转移模型分析了NDVI变化的时空差异，并构建了基于耦合协调度理论和Pettitt检验方法的NDVI与降水关系的变异诊断方法，识别了黄土高原地区NDVI与降水关系的突变点，探讨了降水对NDVI变化的影响以及造成NDVI与降水关系变化的原因。结果表明：（1）黄土高原地区73.49%面积的NDVI在1998-2017年有呈现显著增加趋势（P<0.05），大部分地区NDVI在未来依旧呈现增加趋势；（2）黄土高原地区丘陵沟壑区与高原沟壑区的NDVI增加幅度大于黄土高原地区整体的增加幅度，而北部风沙区和农灌区以及黄土高原地区边界区域的NDVI增加滞后于区域整体变化；（3） NDVI与降水耦合协调程度逐年增强，两者关系在2006年发生显著突变（P<0.05）；（4） NDVI呈现显著增加区域降水明显高于不显著变化区域（P<0.05），降水对NDVI变化存在一定影响，在丘陵沟壑区、高原沟壑区北部和东部河谷及土石山区北部NDVI和降水存在显著正相关关系（P<0.05），然而黄土高原地区大部分区域的降水并不存在显著变化趋势（P>0.05），因此造成黄土高原地区NDVI与降水关系在2006年发生显著突变的主要原因应该是人类活动（P<0.05）。研究成果有助于进一步理解黄土高原植被变化与降水的相互作用，为黄土高原生态建设和水土流失治理提供一定的科学支撑。     

辽宁省菜田生态系统组分优势值与系统优势度分析

辽宁省菜田生态系统组分优势值与系统优势度分析周宝利，葛晓光李宁义（沈阳农业大学园艺系，１１０１６１）（沈阳市城建中专，１１００１３）ＡｎａｌｙｓｉｓｏｎＳｕｐｅｒｉｏｒｉｔｙＶａｌｕｅａｎｄＤｏｍｉｎａｎｃｅＤｅｇｒｅｅｏｆＶａｒｉｏｕｓＣｏｍｐｏｎ...     

A hybrid behavioural rule of adaptation and drift explains the emergent architecture of antagonistic networks

Ecological processes that can realistically account for network architectures are central to our understanding of how species assemble and function in ecosystems. Consumer species are constantly selecting and adjusting which resource species are to be exploited in an antagonistic network. Here we incorporate a hybrid behavioural rule of adaptive interaction switching and random drift into a bipartite network model. Predictions are insensitive to the model parameters and the initial network structures, and agree extremely well with the observed levels of modularity, nestedness and node-degree distributions for 61 real networks. Evolutionary and community assemblage histories only indirectly affect network structure by defining the size and complexity of ecological networks, whereas adaptive interaction switching and random drift carve out the details of network architecture at the faster ecological time scale. The hybrid behavioural rule of both adaptation and drift could well be the key processes for structure emergence in real ecological networks.