ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses.

Genotoxic stress triggers the activation of checkpoints that delay cell-cycle progression to allow for DNA repair. Studies in fission yeast implicate members of the Rad family of checkpoint proteins, which includes Rad17, Rad1, Rad9 and Hus1, as key early-response elements during the activation of both the DNA damage and replication checkpoints. Here we demonstrate a direct regulatory linkage between the human Rad17 homologue (hRad17) and the checkpoint kinases, ATM and ATR. Treatment of human cells with genotoxic agents induced ATM/ATR-dependent phosphorylation of hRad17 at Ser 635 and Ser 645. Overexpression of a hRad17 mutant (hRad17AA) bearing Ala substitutions at both phosphorylation sites abrogated the DNA-damage-induced G2 checkpoint, and sensitized human fibroblasts to genotoxic stress. In contrast to wild-type hRad17, the hRad17AA mutant showed no ionizing-radiation-inducible association with hRad1, a component of the hRad1-hRad9-hHus1 checkpoint complex. These findings demonstrate that ATR/ATM-dependent phosphorylation of hRad17 is a critical early event during checkpoint signalling in DNA-damaged cells.     

铁兰的结构及其作为重金属生物监测器在空气污染评估研究中的应用(英文)

铁兰是一种不从土壤汲取养分的气生植物,在很多国家被用于空气污染的监测研究。虽然铁兰作为生物监测被广泛报道,但却很少有关于铁兰自身结构与其作为生物监测器间相关性的研究。由于它们从降水中吸收水分、养料以及大气污染物,因此,通过检测其组织中累积的重金属即可判断空气的主要污染源。为了进行环境监测,常需要依据土地使用类型、人类活动范围以及距离重金属源的距离进行分类采样,并且要区分农业、城镇、工业及交通区域,铁兰因其广泛的生长适应性、低廉的成本、可长期在不同区域生长并易于采样,被许多研究者认为是环境污染监测中重金属富集的理想植物。     

油中水滴静电聚并微观机理研究

利用电场对多相体系进行分离处理广泛应用于石油化工等行业,电场力作用下液滴间的相互运动聚并是聚结的基础和前提条件.本文从液滴间静电力学模型出发,通过动态微观实验对液滴的聚并过程进行了完整的记录和分析,确定不同实验条件下液滴的聚并方式和角度,以及液滴从静止状态到发生相对运动时的临界条件.结果发现当两等大液滴间距与液滴半径之比大于1时,液滴间中心连线与电场力夹角θ<54.7°或θ>125.3°,两液滴间作用力表现为吸引力,当液滴间距较小时,能产生聚结的最大倾角增大为81.3°.液滴间相对距离增大时,移动临界电场强度迅速升高,较大液滴发生相对移动所需的场强低于小颗粒液滴.实验结果验证了相关理论,进一步完善了静电聚结机理.     

Stationarity tests in time series model building

Optimum non-parametric tests for stationarity of a stochastic process against location and scale shift alternatives are explored. Usefulnesss of these tests in detecting a suitable differencing transformation that reduces a non-stationary time series to a stationary one is illustrated with a number of previously analysed real life data.     

Distribution of mast cells in the mucous membrane of the human nasopharynx

Zusammenfassung Die Mastzellen sind in der Schleimhaut des Naso-Pharynx-Gebiets ubiquitär, und ihre Zahl ist in den seitlichen Wänden erhöht. Es gibt aber keine Verteilungsunterschiede in den vier untersuchten Rassengruppen.     

Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision

Rod and cone photoreceptors detect light and relay this information through a multisynaptic pathway to the brain by means of retinal ganglion cells (RGCs). These retinal outputs support not only pattern vision but also non-image-forming (NIF) functions, which include circadian photoentrainment and pupillary light reflex (PLR). In mammals, NIF functions are mediated by rods, cones and the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). Rod-cone photoreceptors and ipRGCs are complementary in signalling light intensity for NIF functions. The ipRGCs, in addition to being directly photosensitive, also receive synaptic input from rod-cone networks. To determine how the ipRGCs relay rod-cone light information for both image-forming and non-image-forming functions, we genetically ablated ipRGCs in mice. Here we show that animals lacking ipRGCs retain pattern vision but have deficits in both PLR and circadian photoentrainment that are more extensive than those observed in melanopsin knockouts. The defects in PLR and photoentrainment resemble those observed in animals that lack phototransduction in all three photoreceptor classes. These results indicate that light signals for irradiance detection are dissociated from pattern vision at the retinal ganglion cell level, and animals that cannot detect light for NIF functions are still capable of image formation.     

IgH class switching and translocations use a robust non-classical end-joining pathway

Immunoglobulin variable region exons are assembled in developing B cells by V(D)J recombination. Once mature, these cells undergo class-switch recombination (CSR) when activated by antigen. CSR changes the heavy chain constant region exons (Ch) expressed with a given variable region exon from Cmu to a downstream Ch (for example, Cgamma, Cepsilon or Calpha), thereby switching expression from IgM to IgG, IgE or IgA. Both V(D)J recombination and CSR involve the introduction of DNA double-strand breaks and their repair by means of end joining. For CSR, double-strand breaks are introduced into switch regions that flank Cmu and a downstream Ch, followed by fusion of the broken switch regions. In mammalian cells, the 'classical' non-homologous end joining (C-NHEJ) pathway repairs both general DNA double-strand breaks and programmed double-strand breaks generated by V(D)J recombination. C-NHEJ, as observed during V(D)J recombination, joins ends that lack homology to form 'direct' joins, and also joins ends with several base-pair homologies to form microhomology joins. CSR joins also display direct and microhomology joins, and CSR has been suggested to use C-NHEJ. Xrcc4 and DNA ligase IV (Lig4), which cooperatively catalyse the ligation step of C-NHEJ, are the most specific C-NHEJ factors; they are absolutely required for V(D)J recombination and have no known functions other than C-NHEJ. Here we assess whether C-NHEJ is also critical for CSR by assaying CSR in Xrcc4- or Lig4-deficient mouse B cells. C-NHEJ indeed catalyses CSR joins, because C-NHEJ-deficient B cells had decreased CSR and substantial levels of IgH locus (immunoglobulin heavy chain, encoded by Igh) chromosomal breaks. However, an alternative end-joining pathway, which is markedly biased towards microhomology joins, supports CSR at unexpectedly robust levels in C-NHEJ-deficient B cells. In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations.