Ethics of community engagement in field trials of genetically modified mosquitoes

Effective community engagement is an important legal, ethical, and practical prerequisite for conducting field trials of genetically modified mosquitoes, because these studies can substantially impact communities and it is usually not possible to obtain informed consent from each community member. Researchers who are planning to conduct field trials should develop a robust community engagement strategy that meets widely recognized standards for seeking approval from the affected population, such as timeliness, consent, information sharing, transparency, understanding, responsiveness, mutual understanding, inclusiveness, and respectfulness. Additional research is needed on the effectiveness of different methods of engaging communities in field trials of genetically modified mosquitoes and how to respond to public opposition to genetically modified organisms. For research programs involving the genetic modification of disease vectors to move forward, they must have public acceptance and support, which cannot be achieved without effective community engagement.     

Tackling the epigenome in the pluripotent stem cells

Embryonic stem cells are unique in their abilities of self-renewal and to differentiate into many, if not all, cellular lineages. Transcrip- tional regulation, epigenetic modifications and chromatin structures are the key modulators in controlling such pluripotency nature of embryonic stem cell genomes, particularly in the developmental decisions and the maintenance of cell fates. Among them, epigenetic regulation of gene expression is mediated partly by covalent modifications of core histone proteins including methylation, phosphoryla- tion and acetylation. Moreover, the chromatins in stem cell genome appear as a highly organized structure containing distinct functional domains. Recent rapid progress of new technologies enables us to take a global, unbiased and comprehensive view of the epigenetic modifications and chromatin structures that contribute to gene expression regulation and cell identity during diverse developmental stages. Here, we summarized the latest advances made by high throughput approaches in profiling epigenetic modifications and chromatin con- formations, with an emphasis on genome-wide analysis of histone modifications and their implications in pluripotency nature of embry- onic stem cells.     

To identify impacts in variable systems using anomalous changes: a salt marsh example

A method is proposed to identify impacts of habitat modification in cases where it is difficult to site experimental and control samples. This problem occurs especially in heterogeneous systems, but may pose difficulties in any field experimental situation. The method is relevant to the situation where treated (modified) and untreated sites are spread over a range of habitat types. Types of change are identified and compared to treatments. If a specific change type is associated with a particular treatment then it is likely that the change is causally related to the treatment. There are five stages in the analysis. First, the classes or states of the sample sites, over a period of time, are identified (by numerical classification). Second, for each sample site, the sequence of states is listed. Third, transition matrices are made for each sample site to show the changes which have occurred. Fourth, the transition matrices are classified, to identify types of change. Finally, we use the Chisquared test to indicate whether the treated and untreated sites are associated with particular types of change. As an example, we refer to habitat modification to manage salt-marsh mosquitoes and we evaluate impacts on the environment mainly through changes to the vegetation. We consider that the method has potential to identify changes in heterogeneous systems even though little change was identified in the particular salt marsh studied.     

低能铁离子束对原卟啉IX二钠盐的辐照效应研究

110ke V Fe^ 离子注入原卟啉IX二钠盐薄膜亲品后的一些谱学分析结果表明,低能铁离子束辐照可以导致生物分子的损伤和化学改性,并且初步证实注入铁离子在样品分子中慢化沉积后形成含铁的金属络合物,即注入铁离子的质量沉积。     

单分子实时测序及其在微生物表观遗传学中的应用

表观遗传学对于微生物的生命进程起着重要作用。由限制-修饰系统调控的DNA修饰参与微生物的免疫防御系统,无限制-修饰系统调控的DNA修饰通过调控基因表达影响表型。然而,表观遗传信息还没有被常规地作为DNA信息收集分析。基于对DNA合成反应的动力学分析,单分子实时测序技术可以在获得基本序列数据的同时实现对被修饰核苷酸的检测。这个技术为微生物中已知DNA修饰的研究提供了新的平台,也为新型DNA修饰的发现做好准备。本文综述了单分子实时测序技术及其在微生物表观遗传学中的应用。     

壳聚糖的化学改性及其在生物医药领域的应用进展

本文综述了近年来壳聚糖的酰化、羧甲基化、接枝、烷基化和交联等化学改性方法及其在生物医用高分子方面的应用进展,总结了壳聚糖改性及其应用过程中存在的问题并对其发展趋势作了预测。     

Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells

Base excision repair （BER） is an evolutionarily conserved process for maintaining genomic integrity by eliminating several dozen damaged （oxidized or aikylated） or inappropriate bases that are generated endogenously or induced by genotoxicants, predominantly, reactive oxygen species （ROS）. BER involves 4-5 steps starting with base excision by a DNA glycosylase, followed by a common pathway usually involving an AP-endonuclease （APE） to generate 3＇ OH terminus at the damage site, followed by repair synthesis with a DNA polymerase and nick sealing by a DNA iigase. This pathway is also responsible for repairing DNA single-strand breaks with blocked termini directly generated by ROS. Nearly all glycosylases, far fewer than their substrate lesions particularly for oxidized bases, have broad and overlapping substrate range, and could serve as back-up enzymes in vivo. In contrast, mammalian cells encode only one APE, APEI, unlike two APEs in lower organisms. In spite of overall similarity, BER with distinct subpathways in the mammals is more complex than in E. coli. The glycosylases form complexes with downstream proteins to carry out efficient repair via distinct subpathways one of which, responsible for repair of strand breaks with 3＇ phosphate termini generated by the NEIL family glycosylases or by ROS, requires the phosphatase activity of polynucleotide kinase instead of APE1. Different complexes may utilize distinct DNA polymerases and iigases. Mammalian glycosylases have nonconserved extensions at one of the termini, dispensable for enzymatic activity but needed for interaction with other BER and non-BER proteins for complex formation and organeile targeting. The mammalian enzymes are sometimes covalently modified which may affect activity and complex formation. The focus of this review is on the early steps in mammalian BER for oxidized damage.     

Sequential abundant ion fragmentation analysis (SAIFA): an alternative approach for phosphopeptide identification using an ion trap mass spectrometer

Phosphorylation has been the most studied of all the posttranslational modifications of proteins. Mass spectrometry has emerged as a powerful tool for phosphomapping on proteins/peptides. Collision-induced dissociation (CID) of phosphopeptides leads to the loss of phosphoric or metaphosphoric acid as a neutral molecule, giving an intense neutral loss product ion in the mass spectrum. Dissociation of the neutral loss product ion identifies peptide sequence. This method of data-dependent constant neutral loss (DDNL) scanning analysis has been commonly used for mapping phosphopeptides. However, preferential losses of groups other than phosphate are frequently observed during CID of phosphopeptides. Ions that result from such losses are not identified during DDNL analysis due to predetermined scanning for phosphate loss. In this study, we describe an alternative approach for improved identification of phosphopeptides by sequential abundant ion fragmentation analysis (SAIFA). In this approach, there is no predetermined neutral loss molecule, thereby undergoing sequential fragmentation of abundant peak, irrespective of the moiety lost during CID. In addition to improved phosphomapping, the method increases the sequence coverage of the proteins identified, thereby increasing the confidence of protein identification. To the best of our knowledge, this is the first report to use SAIFA for phosphopeptide identification.