ECVAM's response to the changing political environment for alternatives: consequences of the European Union chemicals and cosmetics policies

The European Centre for the Validation of Alternative Methods (ECVAM) has restructured its services by directly targeting the animal tests that need to be replaced. In view of the short time-lines for making available and implementing validated methods, ECVAM is offering to steer the process by bringing together the inputs of stakeholders and encouraging the early involvement of regulators. In essence, steering groups formed by ECVAM senior staff, and complemented with external experts, will carry out the project management and will coordinate the various inputs.     

Report of the EPAA-ECVAM workshop on the validation of Integrated Testing Strategies (ITS)

The use of Integrated Testing Strategies (ITS) permits the combination of diverse types of chemical and toxicological data for the purposes of hazard identification and characterisation. In November 2008, the European Partnership for Alternative Approaches to Animal Testing (EPAA), together with the European Centre for the Validation of Alternative Methods (ECVAM), held a workshop on Overcoming Barriers to Validation of Non-animal Partial Replacement Methods/Integrated Testing Strategies, in Ispra, Italy, to discuss the extent to which current ECVAM approaches to validation can be used to evaluate partial replacement in vitro test methods (i.e. as potential ITS components) and ITS themselves. The main conclusions of these discussions were that formal validation was only considered necessary for regulatory purposes (e.g. the replacement of a test guideline), and that current ECVAM approaches to validation should be adapted to accommodate such test methods. With these conclusions in mind, a follow-up EPAA-ECVAM workshop was held in October 2009, to discuss the extent to which existing validation principles are applicable to the validation of ITS test methods, and to develop a draft approach for the validation of such test methods and/or overall ITS for regulatory purposes. This report summarises the workshop discussions that started with a review of the current validation methodologies and the presentation of two case studies (skin sensitisation and acute toxicity), before covering the definition of ITS and their components, including their validation and regulatory acceptance. The following main conclusions/recommendations were made: that the validation of a partial replacement test method (for application as part of a testing strategy) should be differentiated from the validation of an in vitro test method for application as a stand-alone replacement, especially with regard to its predictive capacity; that, in the former case, the predictive capacity of the whole testing strategy (rather than of the individual test methods) would be more important, especially if the individual test methods had a high biological relevance; that ITS allowing for flexible and ad hoc approaches cannot be validated, whereas the validation of clearly defined ITS would be feasible, although practically quite difficult; and that test method developers should be encouraged to develop and submit to ECVAM not only full replacement test methods, but also partial replacement methods to be placed as parts of testing strategies. The added value from the formal validation of testing strategies, and the requirements needed in view of regulatory acceptance of the data, require further informed discussion within the EPAA forum on the basis of case studies provided by industry.     

miR‐134 inhibits non‐small cell lung cancer growth by targeting the epidermal growth factor receptor

The epidermal growth factor receptor (EGFR) is frequently activated in a wide range of solid tumours and represents an important therapeutic target. MicroRNAs (miRNAs) have recently been recognized as a rational and potential modality for anti‐EGFR therapies. However, more EGFR‐targeting miRNAs need to be explored. In this study, we identified a novel EGFR‐targeting miRNA, miRNA‐134 (miR‐134), in non‐small‐cell lung cancer (NSCLC) cell lines. Luciferase assays confirmed that EGFR is a direct target of miR‐134. In addition, the overexpression of miR‐134 inhibited EGFR‐related signaling and suppressed NSCLC cells proliferation by inducing cell cycle arrest and/or apoptosis, suggesting that miR‐134 functions as a tumour suppressor in NSCLC. Further mechanistic investigation including RNAi and rescue experiments suggested that the down‐regulation of EGFR by miR‐134 partially contributes to the antiproliferative role of miR‐134. Last, in vivo experiments demonstrated that miR‐134 suppressed tumour growth of A549 xenograft in nude mice. Taken together, our findings suggest that miR‐134 inhibits non‐small cell lung cancer growth by targeting the EGFR.     

激光技术在果树育种的应用

在激光果树育种中,激光的生物效应不仅取决于辐照时的激光参数,也取决于被辐照组织的部位、辐照季节等。本文对如何预选激光参数,并对激光诱变生物效应的机制均进行了探讨。紫外和可见激光的诱变机制主要是光化学反应;红外激光的诱变机制,在强激励方式下主要是多光子吸收,在弱激励时则热效应和非热的相干共振效应同时存在。     

Schwann cells promote neurite outgrowth of dorsal root ganglion neurons through secretion of nerve growth factor

The transplantation of Schwann cells (SCs) could successfully promote axonal regeneration. This is likely to attribute to the adhesion molecules expression and growth factors secretion of SCs. But which factor(s) play a key role has not been precisely studied. In this study, an outgrowth assay using dorsal root ganglia (DRG) neuron-SC co-culture system in vitro was performed. Co-culture of SCs or application of SC-conditioned medium (CM) substantially and significantly increased DRG neurite outgrowth. Further, nerve growth factor and NGF receptor (TrkA) mRNA were highly expressed in Schwann cells and DRG neuron, respectively. The high concentration of NGF protein was detected in SC-CM. When K-252a, a specific inhibitor of NGF receptor was added, DRG neurite outgrowth was significantly decreased in a concentration-dependent manner. These data strongly suggest that SCs play important roles in neurite outgrowth of DRG neurons by secreted NGF.     

滇金丝猴分布区森林面积变化的时空特征及其影响因素

森林生态系统是滇金丝猴(Rhinopithecus bieti)的主要生境,森林面积变化会直接影响滇金丝猴的生存。本研究基于全球森林变化(Global Forest Change)数据,采用Theil-Sen趋势分析和Mann-Kendall检验、热点分析与地理探测器模型等方法,探讨了滇金丝猴分布区2001—2019年森林面积变化的时空特征及其影响因素。结果表明:(1)近20年间,滇金丝猴分布区森林面积变化总量为3.81×10~4 hm~2,约占研究区森林面积的2.44%,逐年森林面积变化呈现较大的年际波动,其中5个保护地森林面积变化总量达5456 hm~2,约占研究区森林面积变化总量的14.3%,老君山风景区和云岭保护区森林面积变化的比例较高;(2)滇金丝猴分布区森林面积变化趋于缓和,其中森林面积减少呈现显著增加的区域面积为1.03×10~5 hm~2,占整个研究区面积的2.9%;森林面积减少呈现显著减少的区域面积为3.05×10~5 hm~2,占整个研究区面积的7.9%;同时森林面积变化的热点区域面积呈不断下降的趋势;(3)滇金丝猴分布区森林面积变化呈现向低海拔、高坡度转移的趋势;...