Translational research involving oxidative stress and diseases of aging

There is ample mounting evidence that reactive oxidant species are exacerbated in inflammatory processes, many pathological conditions, and underlying processes of chronic age-related diseases. Therefore there is increased expectation that therapeutics can be developed that act in some fashion to suppress reactive oxidant species and ameliorate the condition. This has turned out to be more difficult than at first expected. Developing therapeutics for indications in which reactive oxidant species are an important consideration presents some unique challenges. We discuss important questions including whether reactive oxidant species should be a therapeutic target, the need to recognize the fact that an antioxidant in a defined chemical system may be a poor antioxidant operationally in a biological system, and the importance of considering that reactive oxidant species may accompany the disease or pathological system rather than being a causative factor. We also discuss the value of having preclinical models to determine if the processes that are important in causing the disease under study are critically dependent on reactive oxidant species events and if the therapeutic under consideration quells these processes. In addition we discuss measures of success that must be met in commercial research and development and in preclinical and clinical trials and discuss as examples our translational research effort in developing nitrones for the treatment of acute ischemic stroke and as anti-cancer agents.     

分子影像:转化医学的重要工具和主要路径

随着基础医学与临床医学脱节现象的日益凸显,作为二者之间连接纽带和桥梁的转化医学越来越受到重视.近年来,转化医学在美、欧等西方国家迅速发展,在我国也正成为"十二五"期间医学领域的重要发展方向之一.分子影像作为现代分子生物学与先进医学影像技术相结合的产物,可以利用影像方法对活体内分子的生物化学过程进行定性和定量研究,是将基...     

人类疾病动物模型是医药创新研究的前沿

人类疾病动物模型对医药研究起着支撑作用,是进行医药研究的必备工具之一.本文阐述了人类疾病动物模型在医药研究中所能发挥的作用,以及在医药研究的历史中所做出的贡献.最后,对疾病动物模型在医药创新研究中应用的前沿进行了展望.     

抑郁症动物模型的转换研究

据世界卫生组织预测,抑郁症将成为“2020年全球疾病负担”排名第二的重大疾病,防治抑郁症的创新药物研发已成为医药科学发展的重要内容.本文在总结近年来关于抑郁症临床治疗和抑郁症动物模型进展的基础上,围绕“如何提高抑郁症动物模型临床预测效度”这一亟待解决的问题,采用“转化医学”的研究模式,提出关于抑郁症动物模型转换研究的一些策略,以期能为建立临床预测效度高的抑郁症动物模型和创新抗抑郁药物研发的革命性突破奠定基础和提供思路.     

中国入侵生物学学科的构建与发展

自英国生态学家查尔斯.艾尔顿1958年撰写的《动植物的入侵生态学》出版至今,半个世纪已经过去,这部著作被公认为是生物入侵在科学研究方面的开端。这期间生物入侵研究经历了萌芽期（20世纪80年代之前）、成长期（20世纪80年代）和快速发展期（20世纪90年代末期至今）。在这个过程中,越来越多的概念、假说、方法和技术被提出和整合到生物入侵研究之中,由此催生了一门生态学领域的新兴学科——入侵生物学。本文在对近50年来生物入侵专著和论文的统计分析基础上,介绍了国际生物入侵研究的发展脉络和现状。同时综述了中国入侵生物学在基础和应用研究方面的相关进展,着重阐述了主要科学问题（＂入侵潜力与成功入侵的关系＂、＂入侵种种群的扩张与扩散＂、＂入侵种的生态适应性与进化＂及＂本地生态系统对入侵的响应及可入侵性＂）和预防与控制的技术体系（风险评估与早期预警、检测与监测、狙击与灭除、生物防治、生态修复与干扰调控）,并进一步介绍了中国入侵生物学学科体系的构建和框架,提出入侵生物学是研究外来物种的入侵性与生态系统的可入侵性,以及外来物种预防与控制的科学,是一门多领域交叉的学科。最后展望和讨论了中国入侵生物学学科发展可能遇到的一些问题。     

Category learning in rodents using touchscreen-based tasks

Categorization is a fundamental cognitive function that organizes our experiences into meaningful “chunks.” This category knowledge can then be generalized to novel stimuli and situations. Multiple clinical populations, including people with Parkinson's disease, amnesia, autism, ADHD and schizophrenia, have impairments in the acquisition and use of categories. Although rodent research is well suited for examining the neural mechanisms underlying cognitive functions, many rodent cognitive tasks have limited translational value. To bridge this gap, we use touchscreens to permit greater flexibility in stimulus presentation and task design, track key dependent measures, and minimize experimenter involvement. Touchscreens offer a valuable tool for creating rodent cognitive tasks that are directly comparable to tasks used with humans. Touchscreen tasks are also readily used with cutting-edge neuroscientific methods that are difficult to do in humans such as optogenetics, chemogenetics, neurophysiology and calcium imaging (using miniscopes). In this review, we show advantages of touchscreen-based tasks for studying category learning in rats. We also address multiple factors for consideration when designing category learning tasks, including the limitations of the rodent visual system, experimental design, and analysis strategies.     

象甲科昆虫转录组研究进展

转录组是细胞在特定发育阶段或生理条件下的全部转录本及其数量总和,并能揭示特定状态下的基因表达模式及分子机理。象甲科昆虫拥有动物界中最多的物种种类,该科许多昆虫也是我国粮食仓储和农林产业上的重大害虫。通过研究象甲科昆虫转录组,从分子水平揭示其生命过程中相关的基因及其功能,对寻找害虫防治的新方法具有重要意义。本文对象甲科昆虫转录组研究现状进行了浅析,涉及象甲科不同发育阶段基因差异、昆虫触角、与植物互作、防治、免疫机制、进化、基因沉默7个方面的分析,可在理论上丰富对象甲科昆虫遗传发育、免疫、潜在RNA干扰靶点筛选等方面的理解,并在此基础上提出了象甲科转录组今后的研究热点与应用前景,为害虫防控提供理论指导。     

CLARIFYING APPEALS TO DIGNITY IN MEDICAL ETHICS FROM AN HISTORICAL PERSPECTIVE

Over the past few decades the concept of (human) dignity has deeply pervaded medical ethics. Appeals to dignity, however, are often unclear. As a result some prefer to eliminate the concept from medical ethics, whereas others try to render it useful in this context. We think that appeals to dignity in medical ethics can be clarified by considering the concept from an historical perspective. Firstly, on the basis of historical texts we propose a framework for defining the concept in medical debates. The framework shows that dignity can occur in a relational, an unconditional, a subjective and a Kantian form. Interestingly, all forms relate to one concept since they have four features in common: dignity refers, in a restricted sense, to the 'special status of human beings'; it is based on essential human characteristics; the subject of dignity should live up to it; and it is a vulnerable concept, it can be lost or violated. We argue that being explicit about the meaning of dignity will prevent dignity from becoming a conversation-stopper in moral debate. Secondly, an historical perspective on dignity shows that it is not yet time to dispose of dignity in medical ethics. At least Kantian and relational dignity can be made useful in medical ethics.     

Assessing nitrate leaching during the three‐first years of Miscanthus × giganteus from on‐farm measurements and modeling

Miscanthus × giganteus is often regarded as one of the most promising crops to produce sustainable bioenergy. This perennial crop, renowned for its high productivity associated with low input requirements, in particular regarding fertilizers, is thought to have low environmental impacts, but few data are available to confirm this. Our study aimed at assessing nitrate leaching from Miscanthus × giganteus crops in farmers' fields, thus including a wide range of soil and cropping system conditions. We focused on the first years of growth after planting as experimental studies have suggested that Miscanthus × giganteus, once established, results in low nitrate leaching. We combined on‐farm measurements and modeling to estimate drainage, leached nitrogen, and nitrate concentration in drainage water in 38 fields located in Center‐East France during two winters (November 2010 to March 2011, November 2011 to March 2012). Nitrate leaching and nitrate concentration in drainage water were on average very low. Nitrate leaching averaged 6 kg N ha^?1 whereas nitrate concentration averaged 12 mg l^?1. These low values are attributable to the low estimates of drainage water (mean = 166 mm) but also to the low soil mineral nitrogen contents measured at the beginning of winter (mean = 37 kg N ha^?1). Our results were, however, very variable, mainly due to the crop age: nitrate leaching and nitrate concentration were critically higher during the winter following the first growth year of Miscanthus × giganteus, reflecting the low development of the crop. This variability was also explained by the range of soil and cropping conditions explored in the on‐farm design: shallow and/or sandy soils as well as fields where establishment failed had a higher risk of nitrate leaching.