Genome-wide approaches to identifying genetic factors in host susceptibility to tuberculosis

Host genetic factors are important in determining susceptibility to Mycobacterium tuberculosis. Genome-wide linkage studies have been performed in humans and in murine models of tuberculosis susceptibility. These studies have identified several important candidate loci for susceptibility to tuberculosis. This is an important step in resolving the complex etiology of the disease.     

Modelling G-protein-coupled receptors for drug design.

The G-protein coupled receptors form a large and diverse multi-gene superfamily with many important physiological functions. As such, they have become important targets in pharmaceutical research. Molecular modelling and site-directed mutagenesis have played an important role in our increasing understanding of the structural basis of drug action at these receptors. Aspects of this understanding, how these techniques can be used within a drug-design programme, and remaining challenges for the future are reviewed.     

Modelling G-protein-coupled receptors for drug design

The G-protein coupled receptors form a large and diverse multi-gene superfamily with many important physiological functions. As such, they have become important targets in pharmaceutical research. Molecular modelling and site-directed mutagenesis have played an important role in our increasing understanding of the structural basis of drug action at these receptors. Aspects of this understanding, how these techniques can be used within a drug-design programme, and remaining challenges for the future are reviewed.     

益生菌的安全性

益生菌是一类重要的微生物调节剂,对人类的营养和健康具有重大的意义。目前,益生菌具有医疗和保健作用毋庸质疑,但是对于益生菌的安全性还存在争议。本文对益生菌的安全性和不安全性研究进行综述,以利于临床正确认识、了解和使用益生菌制剂,对进一步开发利用益生菌也有积极意义。 更多还原     

Role of tyrosine phosphorylation in sperm capacitation / acrosome reaction

Capacitation is an important physiological pre-requisite before the sperm cell can acrosome react and fertilize the oocyte. Recent reports from several laboratories have amply documented that the protein phosphorylation especially at tyrosine residues is one of the most important events that occur during capacitation. In this article, we have reviewed the data from our and other laboratories, and have constructed a heuristic model for the mechanisms and molecules involved in capacitation/acrosome reaction.     

Synthetically modified DNAs as substrates for polymerases

DNA polymerase enzymes process their natural substrates with very high specificity. Yet recent experiments have shown that these enzymes can also process DNA in which the backbone or bases are modified to a surprising degree. Such experiments have important implications in understanding the mechanisms of DNA replication, and suggest important biotechnological uses as well.     

Modelling insect diseases as functional predators

Abstract. Many larval diseases of insects allow no recovery once infected. Furthermore, infected individuals are not able to develop into adults and will not therefore reproduce. A simple modelling approach emphasizes the fact that, accordingly, the agents that cause these diseases are functionally predators. It is important to make this distinction and to be cautious in applying inference drawn from models of parasites to these diseases. Sublethal effects are well known in these insect larval diseases, and models show that they have important dynamical implications. Sublethal effects have received less attention in predator–prey interactions, but their functional relationship with insect diseases emphasizes that nonmortality effects of predators may have correspondingly important dynamical implications.     

Microelectrodes for studying neurobiology

Microelectrodes have emerged as an important tool used by scientists to study biological changes in the brain and in single cells. This review briefly summarizes the ways in which microelectrodes as chemical sensors have furthered the field of neurobiology by reporting on changes that occur on the subsecond time scale. Microelectrodes have been used in a variety of fields including their use by electrophysiologists to characterize neuronal action potentials and develop neural prosthetics. Here we restrict our review to microelectrodes that have been used as chemical sensors. They have played a major role in many important neurobiological findings.     

The role of surgery in the treatment of malignant melanoma

Surgical interventions have important role in the treatment of all stages of malignant melanoma. Surgery is the primary treatment of localized cutaneous melanoma. Excision of the primary tumor makes it possible to set up the histological diagnosis and to determine pathological prognostic factors. Appropriate surgical margin is important for local disease control. Sentinel lymph node biopsy with detailed histological examination has gained prominent importance for correct histological staging and for determining adjuvant oncological treatment. Surgery is the primary treatment of isolated regional metastases. Surgical methods also have a role in the palliative management of distant metastatic melanoma. In the present review the most important issues of the surgical treatment of malignant melanoma have been discussed in detail.     

Deep space and hidden depths: understanding the evolution and ecology of fungal entomopathogens

Entomopathogens are important natural enemies of many insect and mite species and as such have been recognised as providing an important ecosystem service. Indeed, fungal entomopathogens have been widely investigated as biological control agents of pest insects in attempts to improve the sustainability of crop protection. However, even though our understanding of the ecology of fungal entomopathogens has vastly increased since the early 1800s, we still require in-depth ecological research that can expand our scientific horizons in a manner that facilitates widespread adoption of these organisms as efficient biological control agents. Fungal entomopathogens have evolved some intricate interactions with arthropods, plants and other microorganisms. The full importance and complexity of these relationships is only just becoming apparent. It is important to shift our thinking from conventional biological control, to an understanding of an as yet unknown “deep space”. The use of molecular techniques and phylogenetic analyses have helped us move in this direction, and have provided important insights on fungal relationships. Nevertheless, new techniques such as the PhyloChip and pyrosequencing might help us see beyond the familiar fields, into areas that could help us forge a new understanding of the ecology of fungal entomopathogens.     

Towards a better bowl of rice: assigning function to tens of thousands of rice genes

Rice, one of the most important food crops for humans, is the first crop plant to have its genome sequenced. Rice whole-genome microarrays, genome tiling arrays and genome-wide gene-indexed mutant collections have recently been generated. With the availability of these resources, discovering the function of the estimated 41,000 rice genes is now within reach. Such discoveries have broad practical implications for understanding the biological processes of rice and other economically important grasses such as cereals and bioenergy crops.     

Families of discrete kernels for modeling dispersal

Integer lattices are important theoretical landscapes for studying the consequences of dispersal and spatial population structure, but convenient dispersal kernels able to represent important features of dispersal in nature have been lacking for lattices. Because leptokurtic (centrally peaked and long-tailed) kernels are common in nature and have important effects in models, of particular interest are families of dispersal kernels in which the degree of leptokurtosis can be varied parametrically. Here we develop families of kernels on integer lattices with several important properties. The degree of leptokurtosis can be varied parametrically from near 0 (the Gaussian value) to infinity. These kernels are all asymptotically radially symmetric. (Exact radial symmetry is impossible on lattices except in one dimension.) They have separate parameters for shape and scale, and their lower order moments and Fourier transforms are given by simple formulae. In most cases, the kernel families that we develop are closed under convolution so that multiple steps of a kernel remain within the same family. Included in these families are kernels with asymptotic power function tails, which have provided good fits to some observations from nature. These kernel families are constructed by randomizing convolutions of stepping-stone kernels and have interpretations in terms of population heterogeneity and heterogeneous physical processes.     

林木基因克隆研究进展

林木种质资源丰富,种质间遗传差异大,控制林木重要性状的基因克隆及转化对培育优良林木新品种具有很强的实用价值,但许多具有潜在应用价值的林木基因未得到充分发掘和有效分离。近年来,随着各种不同林木cDNA文库的建立,大规模随机EST测序技术的运用以及克隆技术的不断完善,特别是毛果杨（Populustrichocarpa）基因组测序计划的完成,大量与林木重要性状相关的基因被分离和鉴定。这些重要基因的获得为利用转基因技术培育高产、优质、抗逆、抗病虫害的林木新品种奠定了一定的基础。该文综述了20多年来国内外林木基因克隆的研究进展,对基因克隆及其应用过程中亟待解决的问题进行了讨论,并对其发展趋势进行展望。     

肝素酶研究进展

微生物肝素酶是一类作用于肝素和类肝素的多糖裂解酶,在低分子肝素的制备以及肝素类分子的结构解析等领域具有十分重要的应用前景。本文将结合微生物基因组测序的最新进展,综述微生物肝素酶的来源,并对肝素酶的作用机理加以讨论;结合本实验室研究对肝素酶的重组表达及其在低分子肝素生产的应用最新进展作以综述,并对肝素酶其它潜在的应用作以讨论。     

Phosphoinositide-metabolizing enzymes at the interface between membrane traffic and cell signalling

Phosphoinositides (PIs) have long been known to have important roles in cell signalling. During the past decade, it has become clear that these lipids also act as constitutive signals that aid in defining organelle identity, and are short-lived recruiters and regulators of cytoskeletal and membrane dynamics. Recent studies have provided important clues as to how regulated activation of PI-metabolizing enzymes and recruitment of their binding proteins might cooperate in targeting distinct pools of PIs to different cell physiological functions.     

A common neurobiology for pain and pleasure

Pain and pleasure are powerful motivators of behaviour and have historically been considered opposites. Emerging evidence from the pain and reward research fields points to extensive similarities in the anatomical substrates of painful and pleasant sensations. Recent molecular-imaging and animal studies have demonstrated the important role of the opioid and dopamine systems in modulating both pain and pleasure. Understanding the mutually inhibitory effects that pain and reward processing have on each other, and the neural mechanisms that underpin such modulation, is important for alleviating unnecessary suffering and improving well-being.     

植物抗病毒分子机制

在与植物病毒的长期斗争中,植物进化出多种抗病毒机制,其中RNA沉默和R基因介导的病毒抗性是最受人们关注的两种机制.一方面,RNA沉默是植物抵抗病毒侵染的重要手段.植物在病毒侵染过程中可形成病毒来源的双链RNA,经过DCL蛋白的切割、加工形成sRNA,与AGO蛋白结合形成RISC指导病毒RNA的沉默,用于清除病毒.相应地,病毒在与植物的竞争中进化出RNA沉默抑制子,抑制宿主RNA沉默系统以逃避宿主RNA沉默抗病毒反应,增强致病能力.另一方面,植物也进化出R基因介导植物对包括病毒在内的多类病原的抗性.R蛋白直接或间接识别病毒因子,通过一系列的信号转导途径激活植物防御反应,限制病毒的进一步侵染.对植物抗病毒的研究有助于人们对植物抗病分子基础的理解,有重要的科学意义和潜在应用价值.本文综述了植物抗病毒分子机制的重要进展.     

Reverse pharmacology of orexin: from an orphan GPCR to integrative physiology

Orexins, which were initially identified as endogenous peptide ligands for two orphan G-protein coupled receptors (GPCRs), have been shown to have an important role in the regulation of energy homeostasis. Furthermore, the discovery of orexin deficiency in narcolepsy patients indicated that orexins are highly important factors for the sleep/wakefulness regulation. The efferent and afferent systems of orexin-producing neurons suggest interactions between these cells and arousal centers in the brainstem as well as important feeding centers in the hypothalamus. Electrophysiological studies have shown that orexin neurons are regulated by humoral factors, including leptin, glucose, and ghrelin as well as monoamines and acetylcholin. Thus, orexin neurons have functional interactions with hypothalamic feeding pathways and monoaminergic/cholinergic centers to provide a link between peripheral energy balance and the CNS mechanisms that coordinate sleep/wakefulness states and motivated behavior such as food seeking.