番茄疮痂病病原菌分类、抗性遗传和分子标记辅助选择进展

番茄疮痂病是世界上所有番茄种植地区主要的细菌性病害之一，该病能引起严重的产量损失和品质下降，几十年来一直受到育种界的关注。由于该病病原菌存在多个种和小种以及对该病的抗性呈数量性状遗传，因此通过育种途径来改良抗性进展缓慢。分子标记辅助选择为育种家筛选、聚合或累加对多个小种的抗性提供了一种工具。以前的综述对1997年以前在病害的发生、症状、危害、综合防治、遗传分析和育种等方面的研究进行了较为详尽的总结。近年来，在病原菌种与小种的鉴定、抗源的发掘、抗性遗传的分子定位和分子标记辅助选择方面的研究取得了很大进展，传统育种与分子生物学方法有机结合的策略也初见成效。本文将对这些进展进行总结，并对分子标记在番茄疮痂病抗性育种中的应用前景进行讨论。     

Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings

Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail.     

Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain

The identification of neural stem and progenitor cells (NPCs) by in vivo brain imaging could have important implications for diagnostic, prognostic, and therapeutic purposes. We describe a metabolic biomarker for the detection and quantification of NPCs in the human brain in vivo. We used proton nuclear magnetic resonance spectroscopy to identify and characterize a biomarker in which NPCs are enriched and demonstrated its use as a reference for monitoring neurogenesis. To detect low concentrations of NPCs in vivo, we developed a signal processing method that enabled the use of magnetic resonance spectroscopy for the analysis of the NPC biomarker in both the rodent brain and the hippocampus of live humans. Our findings thus open the possibility of investigating the role of NPCs and neurogenesis in a wide variety of human brain disorders.     

Fluorescence-force spectroscopy maps two-dimensional reaction landscape of the holliday junction

Despite the recent advances in single-molecule manipulation techniques, purely mechanical approaches cannot detect subtle conformational changes in the biologically important regime of weak forces. We developed a hybrid scheme combining force and fluorescence that allowed us to examine the effect of subpiconewton forces on the nanometer scale motion of the Holliday junction (HJ) at 100-hertz bandwidth. The HJ is an exquisitely sensitive force sensor whose force response is amplified with an increase in its arm lengths, demonstrating a lever-arm effect at the nanometer-length scale. Mechanical interrogation of the HJ in three different directions helped elucidate the structures of the transient species populated during its conformational changes. This method of mapping two-dimensional reaction landscapes at low forces is readily applicable to other nucleic acid systems and their interactions with proteins and enzymes.     

Host resistance to lung infection mediated by major vault protein in epithelial cells

The airway epithelium plays an essential role in innate immunity to lung pathogens. Ribonucleoprotein particles primarily composed of major vault protein (MVP) are highly expressed in cells that encounter xenobiotics. However, a clear biologic function for MVP is not established. We report here that MVP is rapidly recruited to lipid rafts when human lung epithelial cells are infected with Pseudomonas aeruginosa, and maximal recruitment is dependent on bacterial binding to the cystic fibrosis transmembrane conductance regulator. MVP was also essential for optimal epithelial cell internalization and clearance of P. aeruginosa. These results suggest that MVP makes a substantial contribution to epithelial cell-mediated resistance to infection.     

Relationship Between Allelopathic Effects and Functional Traits of Different Allelopathic Potential Rice Accessions at Different Growth Stages

In this study,effects of temperature,light and their interactions on allelopathic effects and the functional traits specific leaf area(SLA)and stem mass fraction(SMF)of different allelopathic potential rice accessions at different growth stages were analyzed.The main results were as follows:Allelopathic responses to temperature and light varied with different allelopathic potential rice accessions at different growth stages.With the rise of temperature and the extension of photoperiod,allelopathic effect increased firstly and then decreased at 2–3 leaf stage,but increased constantly at the 4–5 and 7–8 leaf stages in strong allelopathic rice accessions[O.longistaminata,F1(O.longistaminata×RD23),F2(RL159 and RL169)].Temperature had significant impact on allelopathic effect without considering light factors,but light showed little effect on rice allelopathy at the same temperature conditions.The greatest allelopathic effect was attained with moderate temperature and long photoperiod at 2–3 leaf stage in strong allelopathic rice accessions,but all the rice accessions showed weak allelopathic effects at the low temperature condition(15oC/10oC),and the influence of different factors on allelopathy followed a general trend as temperatureleaf stagelight,indicating that among the multiple factors impacting rice allelopathy,temperature was the main factor.Allelopathic characteristics of F1 and F2 to various temperature and light were similar to O.longistaminata,showing that allelopathic genes from wild rice can be expressed in its descendants.Temperature and light also had significant effects on SLA and SMF,and rice allelopathy was closely correlative to SLA in strong allelopathic rice accessions at the 4–5 and 7–8 leaf stages,but there was no correlation between rice allelopathy and SMF at different growth stages.These results suggested that rice adjust the relationship between allelopathy and SLA and adapt to the varied environments,and that high temperature and long photoperiod can enhance rice allelopathic activity.