Damage control: a guide to dealing with an infectious break

A change in the microbial status of laboratory animals can represent a disruptive event in the research process. The author suggests a sequence of events from the time a facility learns of a potential infectious "break," through investigation of its source, and its ultimate control.     

美洲斑潜蝇对四季豆的危害损失及防治指标研究

研究结果表明,美洲斑潜蝇危害四季豆时,虫情指数与产量损失率之间有极显正相关,其直线回归方程为Y＝0．7399＋1．0185X,r＝0．9980^**。防治指标：当虫情指数为9．504－19．725时,必须用药防治,控制其为害。     

DNA Damage Checkpoint, Damage Repair, and Genome Stability

Genomic DNA is under constant attack from both endogenous and exogenous sources of DNA damaging agents. Without proper care, the ensuing DNA damages would lead to alteration of genomic structure thus affecting the faithful transmission of genetic information. During the process of evolution, organisms have acquired a series of mechanisms responding to and repairing DNA damage, thus assuring the maintenance of genome stability and faithful transmission of genetic information. DNA damage checkpoint is one such important mechanism by which, in the face of DNA damage, a cell can respond to amplified damage signals, either by actively halting the cell cycle until it ensures that critical processes such as DNA replication or mitosis are complete or by initiating apoptosis as a last resort. Over the last decade, complex hierarchical interactions between the key components like ATM/ATR in the checkpoint pathway and various other mediators, effectors including DNA damage repair proteins have begun to emerge. In the meantime, an intimate relationship between mechanisms of damage checkpoint pathway, DNA damage repair, and genome stability was also uncovered. Reviewed hereinare the recent findings on both the mechanisms of activation of checkpoint pathways and their coordination with DNA damage repair machinery as well as their effect on genomic integrity.     

Ancient DNA Damage

Under favorable conditions DNA can survive for thousands of years in the remains of dead organisms. The DNA extracted from such remains is invariably degraded to a small average size by processes that at least partly involve depurination. It also contains large amounts of deaminated cytosine residues that are accumulated toward the ends of the molecules, as well as several other lesions that are less well characterized.In living cells, DNA molecules continuously suffer chemical insults, which are countered by enzymatic repair mechanisms that maintain the integrity of the genome (Lindahl 1993). On death, these cellular repair mechanisms cease to function. As a consequence, the genome becomes exposed to the unmitigated effects of numerous factors that threaten its stability. These factors include intracellular nucleases, which are no longer sequestered in the cell and can thus gain access to DNA and degrade it, as well as microorganisms that spread in the decaying tissues. Together these factors may lead to the loss of all retrievable DNA. However, under favorable environmental conditions, for example when tissues are frozen or become desiccated quickly after death, these processes become inhibited before the complete destruction of all DNA endogenous to the organism. In these instances other destructive factors, particularly hydrolytic and oxidative processes, become limiting to the time that DNA survives in a tissue.When DNA is extracted and analyzed from ancient samples these destructive factors manifest themselves in three different ways: (i) a reduction in DNA fragment size, (ii) lesions that block the replication of the DNA molecules by polymerases, thus impeding many forms of analysis, and (iii) lesions that cause incorrect nucleotides to be incorporated when the DNA is replicated. Here, we summarize what is known about each of these forms of damage in ancient DNA.     

Damage in transition

Double-stranded DNA breaks (DSBs) are a particularly dangerous form of DNA damage because they can lead to chromosome loss, translocations or truncations. When DSBs occur, many proteins are recruited to the break site; these proteins serve to both initiate DNA repair and to activate a checkpoint response. Repair occurs via one of two pathways: non-homologous end-joining (NHEJ), in which broken DNA ends are directly ligated; or homologous recombination (HR), in which a homologous chromosome is used as a template in a replicative repair process. The checkpoint response is mediated by the phosphatidyl inositol 3-kinase-like kinases, Mec1 and Tel1 (ATR and ATM in humans, respectively). Two recent studies in yeast have significantly increased our understanding of when each of the proteins involved in these processes is localized to a break and, in addition, how their sequential localization is achieved. Specifically, these studies support and expand upon a model in which Tel1 and the NHEJ proteins are the first proteins to localize to the break to initiate signaling and attempt repair, but are subsequently replaced by Mec1 and the HR proteins. This transition is mediated by a cyclin-dependent kinase-dependent initiation of 5'-->3' processing (resection) of the DSB. Thus, the cell-cycle stage at which DSBs occur affects the way in which the DSBs are processed and recognized.     

Methyldopa Liver Damage

Twenty patients are described in whom liver damage appeared to be directly related to the administration of methyldopa. Sixteen had hepatitic syndromes from which they recovered on stopping methyldopa; four of these patients had recurrences of jaundice after a second course of the drug. Features suggestive of active chronic hepatitis were found in two patients. There were two deaths attributed to methyldopa, one of these being in a patient with pre-existing undiagnosed macronodular cirrhosis.     

DNA损伤检验点与损伤修复及基因组稳定性

生物有机体基因组DNA经常会受到内源或外源因素的影响而导致结构发生变化,产生损伤;在长期进化过程中,有机体也相应形成了一系列应对与修复损伤DNA,并维持染色体基因组正常结构功能的机制。其中DNA损伤检验点（DNA damage checkpoint）就是在感应DNA损伤的基础上,对损伤感应信号进行转导,或引起细胞周期的暂停,从而使细胞有足够的时间对损伤DNA进行修复,或最终导致细胞发生凋亡。DNA损伤检验点信号转导途径是一个高度保守的信号感应过程,整个途径大致可以分为损伤感应、信号传递及信号效应3个组成部分。其中3-磷脂酰肌醇激酶家族类成员ATM（ataxia-telangiectasia mutated）和ATR（ataxia-telangiectasia and Rad3-related）活性的增加构成整个途径活化的第一步。它们通过激活下游的效应激酶,Chk2／Chk1,通过协同作用许多其他调控细胞周期、DNA复制、DNA损伤修复及细胞凋亡等过程的蛋白质因子来实现细胞对DNA损伤的高度协调反应。近十几年,随着此领域研究的不断深入,人们逐步揭示了DNA损伤检验点途径发生过程中,各种核心组分通过与不同调节因子、效应因子及DNA损伤修复蛋白间的复杂相互作用,以实现监测感应异常DNA结构并实施相应反应的机制;其中,检验点衔接因子（mediators）及染色质结构,尤其是核小体组蛋白的共价修饰在调控ATM／ATR活性,促进ATM／ATR与底物间的相互作用以及介导DNA损伤位点周围染色质区域上多蛋白复合物在时间与空间上的动态形成发挥着重要的作用。同时,人们也开始发现DNA损伤检验点途径与DNA损伤修复、基因组稳定性以及肿瘤发生等过程之间某些内在的联系。该反应途径在通过协调细胞针对DNA损伤做出各种反应的基础上,直接或间接地参与或调控DNA损伤修复过程,并与DNA损伤修复途径协同作用最终保证染色体基凶组结构的完整性,而检验点途径的改变,则会引起基因组不稳定的发生,包括从突变频率的提高到大范围的染色体重排,以及染色体数量的畸变。如：突变发生在肿瘤形成早期,会大大增加肿瘤发生的几率。文章将对DNA损伤检验点途径机制及其对DNA损伤修复、基因组稳定性影响的最新进展进行综述。     

茶翅蝽在生态苹果园的危害和防治策略

近几年在实施有机生态苹果园的过程中,发现茶翅蝽Halyomorpha halys(Stal)对苹果的危害日益严重,已成为生态苹果园发展的重要难题之一。作者于2006年在北京市昌平区流村镇王家园生态苹果园中,对茶翅蝽的危害进行调查,表明茶翅蝽对苹果危害严重,果园中早、中、晚熟3个品种苹果的为害率分别为28.8%±4.1%、23.4%±4.6%和30.8%±3.6%,在P>0.05水平上无显著差异。在防治策略上,应强调减少苹果园周围茶翅蝽的数量,从而减少迁入量。     

Damage loss assessment and control of the cereal leaf beetle (Coleoptera: Chrysomelidae) in winter wheat

Cereal leaf beetle, Oulema melanopus (L.), invaded northern Alabama and Georgia more than a decade ago and since has become an economic pest of winter wheat and other cereal crops in the southeastern United States. A series of trials was conducted beginning in 1995 to determine optimal rate and timing of applications of selected foliar insecticides for managing cereal leaf beetle in soft red winter wheat. These trials, cage studies with larvae, and a manual defoliation experiment were used to provide information on cereal leafbeetle yield loss relationships and to develop economic decision rules for cereal leaf beetle in soft red winter wheat. Malathion, methomyl, carbaryl, and spinosad effectively controlled larval infestations when treatments were applied after most eggs had hatched. Encapsulated endotoxin of Bacillus thuringiensis, methyl parathion, and disulfoton applied at the lowest labeled rates were not effective treatments. Organophosphate insecticides generally were not effective when applied before most eggs had hatched. The most effective treatments were the low rates of lambda cyhalothrin when applied early while adults were still laying eggs and before or near 50% egg hatch. These early applications applied at or before spike emergence virtually eliminated cereal leaf beetle injury. The manual defoliation study demonstrated that defoliation before spike emergence has greater impact on grain yield and yield components than defoliation after spike emergence. Furthermore, flag leaf defoliation causes more damage than injury to lower leaves. Grain test weight and kernel weight were not affected by larval injury in most trials. Regression of larval numbers and yield losses calculated a yield loss of 12.65% or 459 kg/ha per larva per stem, which at current application costs suggested an economic threshold of 0.4 larvae per stem during the spike emergence to anthesis stages.     

银杏内酯B 对星形胶质细胞氧化损伤的保护作用

目的:探讨银杏内酯B对过氧化氢(H_2O_2)诱导的星形胶质细胞损伤的保护作用及可能机制。方法:星形胶质细胞传代培养,分为阴性对照组(以正常培养液培养),氧化损伤组(100μmol·L~(-1)的H_2O_2作用12 h),银杏内酯B低剂量组(1×10~(-6) mol·L~(-1)银杏内酯B孵育24 h后,加入H_2O_2作用12 h)和银杏内酯B高剂量组(1×10~(-4) mol·L~(-1)银杏内酯B孵育24 h后,加入H_2O_2作用12 h),MTT比色法检测细胞存活率,流式细胞仪检测细胞活性氧(ROS)水平,分光光度计检测上清液中超氧化物歧化酶(SOD)、如谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)的含量。结果:银杏内酯B能抑制氧化损伤引起的细胞活性的下降,降低星形胶质细胞内ROS的生成,促进SOD、GSH-Px水平的升高及MDA水平的下降。结论:银杏内酯B通过提高细胞内SOD、GSH-Px含量,降低细胞内MDA含量发挥其较强的抗氧化作用,从而为其用于治疗神经系统疾病提供可靠的实验依据。     

Paracetamol and Renal Damage

Renal function was assessed in 18 patients who had consumed 2 to 30 kg of paracetamol. No relationship was found between the total amount of paracetamol taken and any aspect of renal function studied. No patient had clinically significant renal impairment. Thirteen of the patients showed no significant deterioration of renal function over a period of about one year during which they consumed an additional mean 2 kg of paracetamol.