Midkine家庭的研究进展

Ｍｉｄｋｉｎｅ家族包括Ｍｉｄｋｉｎｅ（ＭＫ）和肝素结合生长相关分子（ＨＢ－ＧＡＭ）,两种因子的基因结构和氨基酸组成极其相似,是一类新的肝素结合生长／分化因子。胚胎期,ＭＫ和ＨＢ－ＧＡＭ分布广泛,出生后局限于某些特定部位。ＭＫ和ＨＢ－ＧＡＭ可影响神经元和非神经以及肿瘤细胞的存活、增殖和分化,在胚胎发育和肿瘤发生中具有重要作用。     

Recent advances in RNA-protein interaction studies

Conclusions The RNA binding sites for several small proteins have been characterised. These sites include double helical regions with hairpins, bulged bases and internal loops. As seen in Flock House virus structure, some proteins may recognise phosphate backbone of the canonical A-form helix not in a sequence-specific manner. If sequence-specific base contacts are to be made, then the A-helic major groove must be widened. This can be accomplished by introducing bulges, internal loops and hairpin loops into double helical regions. In these cases proteins may recognise both distorted backbone conformations and read out base sequences in a widened major groove. Crystallographic studies on complexes of aminoacyl-tRNA synthetase and tRNA showed that even RNAs with stable tertiary fold undergo substantial structural changes upon binding to the synthetases. The structural variability of RNA as well as the ability of RNA to distort upon protein binding may be crucial in RNA-protein interactions.     

微生物脂肪酶稳定性研究进展

脂肪酶广泛应用于食品、药物、生物燃料、诊断、生物修复、化学品、化妆品、清洁剂、饲料、皮革和生物传感器等工业领域,微生物脂肪酶是商品化脂肪酶的重要来源。高温、酸性、碱性和有机溶剂等恶劣的工业生产环境使得脂肪酶的进一步工业应用受到限制,获取稳定性好的脂肪酶成为打破这一限制的关键环节。本文重点对提高微生物脂肪酶稳定性的策略进行了综述:挖掘极端微生物脂肪酶资源;利用定向进化、理性设计和半理性设计等蛋白质工程策略改造脂肪酶;利用物理吸附、封装、共价结合和交联等酶的固定化技术提高脂肪酶的稳定性;利用物理/化学修饰、表面展示以及多种改良策略相结合提高脂肪酶的稳定性。结合作者前期对酶工程的研究发现,新型酶催化剂的获得应该基于明确的设计思路,结合多种改造方法,基于定向进化-理性设计、定向进化-半理性设计、蛋白质工程-酶的固定化、蛋白质工程-物理/化学修饰、酶的固定化-物理/化学修饰等组合改造,比单一的改造方法具有更高的效率。     

Recent advances in single-cell studies of gene regulation

A mechanistic understanding of gene regulatory network dynamics requires quantitative single-cell data of multiple network components in response to well-defined perturbations. Recent advances in the development of fluorescent biomarkers for proteins, detection of RNA and interactions, microfluidic technology, and high-resolution imaging have set the stage for a host of new studies that elucidate the important roles of stochasticity and cell-cell variability in response to external perturbations. In this review, we briefly describe methods for high-resolution visualization and the control of gene expression, along with application of these novel methods to recent studies involving gene networks.     

Recent advances in single molecule studies of nucleosomes

As the fundamental packing units of DNA in eukaryotes, nucleosomes play a central role in governing DNA accessibility in a variety of cellular processes. Our understanding of the mechanisms underlying this complex regulation has been aided by unique structural and dynamic perspectives offered by single molecule techniques. Recent years have witnessed remarkable advances achieved using these techniques, including the generation of a detailed histone-DNA energy landscape, elucidation of nucleosome disassembly processes, and real-time monitoring of molecular motors interacting with nucleosomes. These and other highlights of single molecule nucleosome studies will be discussed in this review.     

Familial hyperlipoproteinemia in beagles

Canine serum lipoproteins (Lp) were studied by electrophoretic and immunologic techniques. Two of five normal beagles on a regular diet were spontaneously “hyperlipidemic”.Using the double-layer separating gel, polyacrylamide gel (PAG) block electrophoresis method, α₁-, α₂-, and β-Lps were consistently detected. While α₁-Lp was the major serum Lp in normolipidemic dogs, α₂- and β-Lps were elevated in the “hyperlipidemic” animals. The α₁-Lp and α₂-Lp exhibited A₁ and A₂ antigenic components and β-Lp had B and C components. We propose that in all probability α₁- and α₂-Lp have similar A₁, A₂ components, but that β-Lp contains both B and C components. This suggests that α₁- and α₂-Lps, particularly in beagles with familial hyperlipoproteinemia are distinct Lp entities with similar lipid composition and with two common major antigenic components. The albumin fraction of PAG block electrophoretograms contained lipid materials other than free fatty acids. This albumin-lipid complex may be similar to that observed in guinea pig serum. On the basis of this study, the α₂-Lp of dogs is a distinct and important Lp moiety which is elevated in the early stages of both familial and experimental canine hyperlipoproteinemia.