Molecular mechanisms of membrane-associated amyloid aggregation: Computational perspective and challenges

Amyloidogenic proteins are related to a variety of amyloid diseases, such as type 2 diabetes (T2D), Alzheimer's disease (AD) and Parkinson's disease (PD). The amyloid proteins in which this review focuses include amylin, Aβ, tau and α-synuclein. Understanding the molecular mechanisms in which these amyloidogenic proteins interact with membranes is a challenging research to both experimental and computational studies. This review illustrates recent studies on amyloid-membrane interactions, but it mainly focuses on the challenge issues related to experimental techniques to investigate at the molecular level these interactions and provides thoughts and outlook for future computational studies.     

基因组学方法在玉米种质资源研究中的应用

近年来,分子生物学和植物基因组学得到了飞速发展,包括分子标记技术在内的基因组学方法在玉米种质资源研究中得到了广泛应用。本将对玉米种质资源研究的主要领域如玉米的起源和进化、遗传多样性的形成机制及评估、基于多样性的新基因发掘等方面的最新进展进行评述,并提出我国在应用基因组学方法进行玉米种质资源研究的策略。     

腺齿木科系统位置评述

腺齿木科(Trimeniaceae)含2属5种。形态学研究显示腺齿木科具有许多原始性状。最新的分子系统发育研究显示,腺齿木科是现存被子植物的重要基部类群之一。但有关腺齿木科的系统位置存在争议。被子植物(有花植物)的起源与辐射一直是植物系统学家关注的热点。对该科系统位置的研究历史与现状进行评述。     

Building a bacterial orisome: emergence of new regulatory features for replication origin unwinding

Triggering new rounds of chromosomal DNA replication during the bacterial cell cycle is exquisitely regulated, ensuring both proper timing and one round per cycle stringency. A critical first step is stable unwinding of oriC, the chromosomal replication origin, by multiprotein orisome complexes comprising the AAA+ initiator DnaA and modulator proteins that bend DNA. Recently identified oriC-DnaA interactions in Escherichia coli raise important questions regarding the molecular mechanisms that regulate origin unwinding in bacteria. We describe staged binding of E. coli origin recognition proteins and suggest an unwinding switch based on interactions between DnaA-ATP and specialized oriC sites that must be filled during orisome assembly. By focusing multiple regulatory pathways on only a few key oriC DNA-protein interactions, this model includes an efficient way to control unwinding followed by orisome inactivation during the cell cycle. Future studies will determine whether this regulatory scheme is correct and whether it is generally applicable to other bacterial types.     

互叶梅科系统位置评述

互叶梅科 Amborellaceae 一属一种 .形态学研究显示互叶梅 Amborella tricopoda Baill. 具有许多原始性状 .大多数最新的分子系统发育研究显示 ,互叶梅科是现存被子植物的最基部类群 .但有关互叶梅科的系统位置存在争议 .被子植物 有花植物 的起源和辐射一直是植物学家关注的热点 .本文将对该科系统位置的研究历史与现状进行评述     

Environmental metabolomics: a critical review and future perspectives

Environmental metabolomics is the application of metabolomics to characterise the interactions of organisms with their environment. This approach has many advantages for studying organism–environment interactions and for assessing organism function and health at the molecular level. As such, metabolomics is finding an increasing number of applications in the environmental sciences, ranging from understanding organismal responses to abiotic pressures, to investigating the responses of organisms to other biota. These interactions can be studied from individuals to populations, which can be related to the traditional fields of ecophysiology and ecology, and from instantaneous effects to those over evolutionary time scales, the latter enabling studies of genetic adaptation. This review provides a comprehensive and current overview of environmental metabolomics research. We begin with an overview of metabolomic studies into the effects of abiotic pressures on organisms. In the field of ecophysiology, studies on the metabolic responses to temperature, water, food availability, light and circadian rhythms, atmospheric gases and season are reviewed. A section on ecotoxicogenomics discusses research in aquatic and terrestrial ecotoxicology, assessing organismal responses to anthropogenic pollutants in both the laboratory and field. We then discuss environmental metabolomic studies of diseases and biotic–biotic interactions, in particular herbivory. Finally, we critically evaluate the contribution that metabolomics has made to the environmental sciences, and highlight and discuss recommendations to advance our understanding of the environment, ecology and evolution using a metabolomics approach.     

社会性昆虫级型和行为分化机制研究进展

社会性的出现是生物演化过程中的重要革新, 理解社会性的演化和调控机制具有重要的理论和实际意义。社会性昆虫的个体间有着明显的级型分化和劳动分工, 这有利于它们适应复杂的环境变化。理解社会性昆虫如何产生不同的形态、行为和生活史特性, 一直是进化和发育生物学的重要目标。随着测序技术的不断更新及生物信息学的快速发展, 已经有众多关于社会性昆虫级型和行为分化机制的研究报道。本文通过整理社会性昆虫研究的已有成果, 从环境因素、生理调控和分子机制等方面对社会性昆虫级型和行为分化机制相关研究进展进行了综述, 并对未来的研究方向做出了展望。根据现有证据, 社会性昆虫所生活的生物环境(食物营养、信息素、表皮碳氢化合物)和非生物环境(温度、气候等)均能直接或间接影响社会性昆虫级型和行为的分化; 保幼激素、蜕皮激素、类胰岛素及生物胺等内分泌激素和神经激素对社会性昆虫的级型和行为分化也有重要的调控作用; 此外, 遗传因素、新基因等DNA序列或基因组结构上的变化以及表观遗传修饰、基因的差异表达等基因调控机制均能不同程度地影响社会性昆虫的行为分化。本文建议加强昆虫纲其他社会性类群如半翅目蚜虫和缨翅目蓟马等的社会性行为及其演化机制的研究, 以加深对社会性昆虫起源及其行为演化的理解和认识。     

种子发育相关基因的研究进展

种子发育是被子植物繁殖的中心环节,涉及众多基因及其互作。新近的研究集中在雌雄基因组的差异表达、后生过程的控制机理和发育调控网络等方面。对胚和胚乳发育相关基因的研究,可使人们在分子水平上解析种子发育和无融合生殖的分子机制,更有效地开展植物种子产量和品质改良的基因工程。     

Scanning Tunnelling Microscopy and Molecular Modelling of Xanthine Monolayers Self-assembled at the Solid-Liquid Interface: Relevance to the Origin of Life

The development of scanning tunnelling microscopy (STM) has allowed examination of inorganic crystalline surfaces and their interactions with organic adsorbates with unparalleled resolution. As a novel technique in origin of life studies, the application of STM is detailed with particular attention paid to the methods employed in the analysis of organic monolayer structures. STM imaging and molecular modelling of self-assembled monolayers of the purine base, xanthine, formed on the surfaces of graphite and molybdenum disulfide are presented as an example. The putative role of such structures in the origin of life is discussed.     

History of phage research as viewed by a European

Abstract: The history of phage research as the origin of molecular biology is related as seen by a scientist located at that critical time in Geneva. The preponderant influence of Max Delbrück on these developments is traced as a consequence of his personal charisma. Jean Weigle, former professor of experimental physics in Geneva and later research fellow with Delbrück, acted as an important ambassador to the European groups.     

Molecular Mechanisms of Disease-Causing Missense Mutations

Genetic variations resulting in a change of amino acid sequence can have a dramatic effect on stability, hydrogen bond network, conformational dynamics, activity and many other physiologically important properties of proteins. The substitutions of only one residue in a protein sequence, so-called missense mutations, can be related to many pathological conditions and may influence susceptibility to disease and drug treatment. The plausible effects of missense mutations range from affecting the macromolecular stability to perturbing macromolecular interactions and cellular localization. Here we review the individual cases and genome-wide studies that illustrate the association between missense mutations and diseases. In addition, we emphasize that the molecular mechanisms of effects of mutations should be revealed in order to understand the disease origin. Finally, we report the current state-of-the-art methodologies that predict the effects of mutations on protein stability, the hydrogen bond network, pH dependence, conformational dynamics and protein function.     

Morris Goodman’s hominoid rate slowdown: The importance of being neutral

Half a century ago, when the field of molecular evolution did not even exist, Morris Goodman analyzed profiles of immunological interactions between species and reached the following two remarkable conclusions: first, protein evolution slowed down in the human lineage compared to other primate lineages; second, this slowdown was more pronounced for proteins whose functions were likely to be neutral. It took several decades of research to fully grasp these ideas and document the pattern of hominoid rate slowdown. Along the way, studies of hominoid rate slowdown led to major progresses in understanding determinants of neutral molecular evolution, which in turn is used to calibrate rates of adaptive evolution. Furthermore, the growing knowledge on the origin of mutations provides a basis for understanding differential evolutionary rates between sex chromosomes and autosomes, which has deep implications for inferring human evolutionary histories, and other aspects of molecular evolution. Primate genomics in particular stand to provide critical information in these pursuits, due to the abundance of genomic data, relatively rich documentation of life history traits, and several model systems, including our own species.     

Structure of yeast hexokinase-B: I. Preliminary X-ray studies and subunit structure

Initial X-ray diffraction studies of large single crystals of yeast hexokinase-B provide information on its subunit structure and show the crystals to be suitable for a high resolution structure determination. Patterson maps of the native protein crystals suggest that the two 50,000 molecular weight subunits are identical, or very nearly so, and that they are related by an approximate rather than a true diad axis; that is, one subunit is translated relative to the other by 3.6 Å along the molecular symmetry axis. This results in heterologous subunit interactions rather than the isologous interactions expected.     

外生菌根真菌的共生互作和宿主选择机制研究进展

外生菌根真菌作为树木的共生伙伴,是森林生态系统重要组成部分,在森林天然更新、植物抗逆性形成、协助植物吸收限制性营养等方面扮演重要角色。真菌和植物跨界共生具有复杂的分子互作过程,在共生的不同阶段有不同的分子互作机制,其调控反馈网络还有许多未知。基因组与转录组研究技术和方法的进步,为一些新的信号分子、效应蛋白以及相关通路的发现提供了可能。真菌与宿主植物之间营养转移调控对共生的影响也逐渐受到关注,营养相关的转运蛋白对共生的建立和维持提供了物质基础。真菌的宿主选择机制是值得重点关注的领域,由于外生菌根真菌的多谱系起源和演化史中存在多次宿主转换事件,真菌演化出多样的应对机制用来区分相容性宿主、不相容性宿主和非宿主。通过对不同真菌与宿主植物的组学研究,宿主选择机制研究取得了一定进展。本文对近十年来国内外的研究报道进行梳理与总结,并对未来在该领域的探索方向做出展望。     

Cancer stem cell hypotheses: impact on modern molecular physiology and pharmacology research

Although questioned on several occasions, the existence of cancer stem cells (CSCs) has been confirmed by a number of studies on experimental animal models. Nevertheless, it was shown that CSC hypotheses have several limitations and inconsistencies regarding the explanation of CSC origin, CSC identification and isolation, possible heterogeneity within CSC population, as well as methodology issues in some studies that were carried out in order to prove CSC existence. The aim of this article is to give a short and comprehensive review of recent advances concerning CSC hypothesis and to describe its impact on modern molecular physiology and pharmacology research.     

Azospirillum-plant relationships: physiological, molecular, agricultural, and environmental advances (1997-2003)

This review presents a critical and comprehensive documentation and analysis of the developments in agricultural, environmental, molecular, and physiological studies related to Azospirillum cells, and to Azospirillum interactions with plants, based solely on information published between 1997 and 2003. It was designed as an update of previous reviews (Bashan and Levanony 1990; Bashan and Holguin 1997a), with a similar scope of interest. Apart from an update and critical analysis of the current knowledge, this review focuses on the central issues of Azospirillum research today, such as, (i) physiological and molecular studies as a general model for rhizosphere bacteria; (ii) co-inoculation with other microorganisms; (iii) hormonal studies and re-consideration of the nitrogen contribution by the bacteria under specific environmental conditions; (iv) proposed Azospirillum as a non-specific plant-growth-promoting bacterium; (v) re-introduction of the "Additive Hypothesis," which suggests involvement of multiple mechanisms employed by the bacteria to affect plant growth; (vi) comment on the less researched areas, such as inoculant and pesticide research; and (vii) proposes possible avenues for the exploitation of this bacterium in environmental areas other than agriculture.     

Vertebrate limb regeneration and the origin of limb stem cells

The existence of multipotent cells in the adult tissues and organs of those vertebrates that are capable of regeneration has been accepted for decades. Although studies of vertebrate limb regeneration have yet to identify many of the specific molecules involved in regeneration, numerous tissue grafting experiments and studies of cell lineage have contributed significantly to an understanding of the origin, activation, proliferation and cell-cell interactions of these progenitor cells. This has allowed the development of ideas about the regulation of pattern formation to restore the structure and function of lost tissues and organs. An understanding of the molecular mechanisms controlling these processes has lagged behind the dramatic advances achieved with other model organisms. However, given the intense, new research interest in stem cells over the past few years, there is good reason to be encouraged that insights about the biology of mammalian stem cells will accelerate progress in understanding the biology of regeneration in organisms that can regenerate. Advances in regeneration research will then feed back in terms of devising new strategies for therapies to induce regeneration in organisms such as humans that have traditionally been viewed as incapable of regeneration.     

HPA-axis activity in alcoholism: examples for a gene-environment interaction.

Genetic and environmental influences are both known to be causal factors in the development and maintenance of substance abuse disorders. This review aims to focus on the contributions of genetic and environmental research to the understanding of alcoholism and how gene-environment interactions result in a variety of addiction phenotypes. Gene-environment interactions have been reviewed by focusing on one of the most relevant environmental risk factors for alcoholism, stress. This is examined in more detail by reviewing the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and its genetic and molecular components in this disorder. Recent evidence from animal and human studies have shown that the effects of stress on alcohol drinking are mediated by core HPA axis genes and are associated with genetic variations in those genes. The findings of the studies discussed here suggest that the collaborations of neuroscience, psychobiology and molecular genetics provide a promising framework to elucidate the exact mechanisms of gene-environment interactions as seen to convene upon the HPA axis and effect phenotypes of addiction.     

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

Lipid membranes work as barriers, which leads to inevitable drug-membrane interactions in vivo. These interactions affect the pharmacokinetic properties of drugs, such as their diffusion, transport, distribution, and accumulation inside the membrane. Furthermore, these interactions also affect their pharmacodynamic properties with respect to both therapeutic and toxic effects. Experimental membrane models have been used to perform in vitro assessment of the effects of drugs on the biophysical properties of membranes by employing different experimental techniques. In in silico studies, molecular dynamics simulations have been used to provide new insights at an atomistic level, which enables the study of properties that are difficult or even impossible to measure experimentally. Each model and technique has its advantages and disadvantages. Hence, combining different models and techniques is necessary for a more reliable study. In this review, the theoretical backgrounds of these (in vitro and in silico) approaches are presented, followed by a discussion of the pharmacokinetic and pharmacodynamic properties of drugs that are related to their interactions with membranes. All approaches are discussed in parallel to present for a better connection between experimental and simulation studies. Finally, an overview of the molecular dynamics simulation studies used for drug-membrane interactions is provided.     

Immunological detection of an analogue of the erythroid protein 4.1 in endothelial cells

Endothelial cells (EC) of arterial and venous origin were investigated by indirect immunofluorescence and immunoautoradiography for the presence of red cell membrane 4.1-like protein. By immunofluorescence, EC exhibited a relatively uniform fluorescent staining sometimes of a reticular pattern, distributed over the entire cell. All controls were negative. Immunoblot analysis of EC revealed a cross reactive band of a molecular weight comparable to that of the erythrocyte band 4.1. These findings indicate that endothelial cells of arterial and venous origin express a polypeptide immunologically related to the erythrocyte protein 4.1, which may play an important role in membrane-cytoskeleton interactions.