食线虫菌物胞外蛋白酶基因工程研究进展

在病原线虫的生物防治中 ,利用食线虫菌物在侵染过程中分泌的胞外蛋白酶 (重要毒力因子 )固定线虫并降解线虫体壁显示出巨大的潜力。综述了近年来食线虫菌物胞外蛋白酶的研究概况、目前开展蛋白酶基因工程研究存在的问题及解决策略;对真菌胞外蛋白酶应用于线虫生防和生物医药领域中的前景也进行了评述。     

Iron deficiency: lessons from anemic mice.

Iron is an essential nutrient, and disorders of iron metabolism are common. Nonetheless, intestinal iron absorption and cellular iron transport are poorly understood. Biochemical approaches to elucidating these processes have yielded little in the past decade. As an alternative approach, we have begun to study spontaneous mouse mutants, that have inherited defects in key steps in iron transport. We have undertaken positional cloning of the gene responsible for microcytic anemia (gene symbol mk). This report describes the important characteristics of these mice, and our progress in studying them.     

Evolutionary novelties and losses in geometric morphometrics: a practical approach through hominin molar morphology

Geometric morphometric techniques may offer a promising methodological approach to analyze evolutionary novelties in a quantitative framework. Nevertheless, and despite continuous improvements to this methodology, the inclusion of novel features in these studies presents some difficulties. In the present study, different methods to explicitly include novel traits in geometric morphometric analyses are compared, including homology-free approaches, landmark-based approaches, and combinations of both techniques. The two-dimensional occlusal morphology of the lower second molar in multiple hominin species was chosen to evaluate these methods, as an example of an anatomical structure including one novelty: a distal fifth cusp is present in earlier hominins, and notably absent in many later Homo species. Results reveal that different approaches provide different results, highlighting that the design of the conformations of landmarks has a high impact on the inferred conclusions. Among diverse methods, a combined approach including landmarks, sliding semilandmarks, and only one landmark related to the studied novelty (an indicator of its absence or presence and of its size, when present), was able to directly discern structures with and without the novel feature, circumventing some of the methodological difficulties associated with these traits. This study demonstrates the ability of geometric morphometric techniques to investigate evolutionary novelties and explores the implications of different methods, providing a reference context for future studies.     

The search for loci under selection: trends,biases and progress

Detecting genetic variants under selection using F_ST outlier analysis (OA) and environmental association analyses (EAAs) are popular approaches that provide insight into the genetic basis of local adaptation. Despite the frequent use of OA and EAA approaches and their increasing attractiveness for detecting signatures of selection, their application to field‐based empirical data have not been synthesized. Here, we review 66 empirical studies that use Single Nucleotide Polymorphisms (SNPs) in OA and EAA. We report trends and biases across biological systems, sequencing methods, approaches, parameters, environmental variables and their influence on detecting signatures of selection. We found striking variability in both the use and reporting of environmental data and statistical parameters. For example, linkage disequilibrium among SNPs and numbers of unique SNP associations identified with EAA were rarely reported. The proportion of putatively adaptive SNPs detected varied widely among studies, and decreased with the number of SNPs analysed. We found that genomic sampling effort had a greater impact than biological sampling effort on the proportion of identified SNPs under selection. OA identified a higher proportion of outliers when more individuals were sampled, but this was not the case for EAA. To facilitate repeatability, interpretation and synthesis of studies detecting selection, we recommend that future studies consistently report geographical coordinates, environmental data, model parameters, linkage disequilibrium, and measures of genetic structure. Identifying standards for how OA and EAA studies are designed and reported will aid future transparency and comparability of SNP‐based selection studies and help to progress landscape and evolutionary genomics.     

Diurnal Regulation of Lipid Metabolism and Applications of Circadian Lipidomics

The circadian timing system plays a key role in orchestrating lipid metabolism. In concert with the solar cycle, the circadian system ensures that daily rhythms in lipid absorption, storage, and transport are temporally coordinated with rest-activity and feeding cycles. At the cellular level, genes involved in lipid synthesis and fatty acid oxidation are rhythmically activated and repressed by core clock proteins in a tissue-specific manner. Consequently, loss of clock gene function or misalignment of circadian rhythms with feeding cycles （e.g., in shift work） results in impaired lipid homeostasis. Herein, we review recent progress in circadian rhythms research using lipidomics, i.e., large-scale profiling of lipid metabolites, to characterize circadian-regulated lipid pathways in mammals. In mice, novel regulatory circuits involved in fatty acid metabolism have been identified in adipose tissue, liver, and muscle. Extensive diversity in circadian regulation of plasma lipids has also been revealed in humans using lipidomics and other metabolomics approaches. In future studies, lipidomics platforms will be increasingly used to better understand the effects of genetic variation, shift work, food intake, and drugs on circadian-regulated lipid pathways and metabolic health.     

Proteomic analysis of Korean ginseng (Panax ginseng C.A. Meyer)

Although many reports have been published regarding the pharmacological effects of ginseng, little is known about the biochemical pathways operant in ginsenoside biosynthesis, or the genes involved therein. Proteomics analysis is an approach to elucidate the physiological characteristics and biosynthetic pathways of ginsenosides, main components of ginseng. In this review, we introduced the recent progress in proteomics studies of ginseng (Panax ginseng C.A. Meyer). We briefly reference the genomic analyses of P. ginseng, without which proteomics approaches would have been impossible. Functional genomics studies regarding secondary metabolism in P. ginseng are also introduced here, in order to introduce possible future prospects for further study.     

Neurogenetics: advancing the "next-generation" of brain research

There can be little doubt that genetics has transformed our understanding of mechanisms mediating brain disorders. The last two decades have brought tremendous progress in terms of accurate molecular diagnoses and knowledge of the genes and pathways that are involved in a large number of neurological and psychiatric disorders. Likewise, new methods and analytical approaches, including genome array studies and "next-generation" sequencing technologies, are bringing us deeper insights into the subtle complexities of the genetic architecture that determines our risks for these disorders. As we now seek to translate these discoveries back to clinical applications, a major challenge for the field will be in bridging the gap between genes and biology. In this Overview of Neuron's special review issue on neurogenetics, we reflect on progress made over the last two decades and highlight the challenges as well as the exciting opportunities for the future.     

System-level strategies for studying the metabolism of Mycobacterium tuberculosis

Despite decades of research many aspects of the biology of Mycobacterium tuberculosis remain unclear and this is reflected in the antiquated tools available to treat and prevent tuberculosis and consequently this disease remains a serious public health problem. Important discoveries linking M. tuberculosis's metabolism and pathogenesis have renewed interest in this area of research. Previous experimental studies were limited to the analysis of individual genes or enzymes whereas recent advances in computational systems biology and high throughput experimental technologies now allow metabolism to be studied on a genome scale. Here we discuss the progress being made in applying system level approaches to studying the metabolism of this important pathogen. The information from these studies will fundamentally change our approach to tuberculosis research and lead to new targets for therapeutic drugs and vaccines.     

In vitro methods in the prediction of kinetics of drugs: focus on drug metabolism

The absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of a candidate drug influence its final clinical success. These properties have traditionally been evaluated by using various in vivo animal approaches, but recently, a number of in vitro and in silico methods have been introduced to determine key ADMET features. Basic events, such as absorption through the gut wall, binding to plasma proteins, active and passive transfer through the blood-brain barrier, and various metabolic parameters, can now be screened with rapid in vitro and computer modelling methods. The focus in this short review is on the basic in vitro and in silico methods that are used for studying the metabolism properties of new drug molecules.     

Regulation of plant glucosinolate metabolism

Glucosinolates and their degradation products are known to play important roles in plant interaction with herbivores and micro-organisms. In addition, they are important for human life. For example, some degradation products are flavor compounds and some exhibit anticarcinogenic properties. Recent years have seen great progress made in the understanding of glucosinolate biosynthesis in Arabidopsis thaliana. The core glucosinolate biosynthetic pathway has been revealed using biochemical and reverse genetics approaches. Future research needs to focus on questions related to regulation and control of glucosinolate metabolism. Here we review current status of studies on the regulation of glucosinolate metabolism at different levels, and highlight future research towards elucidating the signaling and metabolic network that control glucosinolate metabolism.     

Purine and pyrimidine biosynthesis in higher plants

Purine and pyrimidine nucleotides have important functions in a multitude of biochemical and developmental processes during the life cycle of a plant. In higher plants the processes of nucleotide metabolism are poorly understood, but it is in principle accepted that nucleotides are essential constituents of fundamental biological functions. Despite of its significance, higher plant nucleotide metabolism has been poorly explored during the last 10–20 years (Suzuki and Takahashi 1977, Schubert 1986, Wagner and Backer 1992). But considerable progress was made on purine biosynthesis in nodules of ureide producing tropical legumes, where IMP-synthesis plays a dominant role in primary nitrogen metabolism (Atkins and Smith 2000, Smith and Atkins 2002). Besides these studies on tropical legumes, this review emphasises on progress made in analysing the function in planta of genes involved in purine and pyrimidine biosynthesis and their impact on metabolism and development.     

An assessment of the use of chimpanzees in hepatitis C research past, present and future: 2. Alternative replacement methods

The use of chimpanzees in hepatitis C virus (HCV) research was examined in the report associated with this paper (1: Validity of the chimpanzee model), in which it was concluded that claims of past necessity of chimpanzee use were exaggerated, and that claims of current and future indispensability were unjustifiable. Furthermore, given the serious scientific and ethical issues surrounding chimpanzee experimentation, it was proposed that it must now be considered redundant--particularly in light of the demonstrable contribution of alternative methods to past and current scientific progress, and the future promise that these methods hold. This paper builds on this evidence, by examining the development of alternative approaches to the investigation of HCV, and by reviewing examples of how these methods have contributed, and are continuing to contribute substantially, to progress in this field. It augments the argument against chimpanzee use by demonstrating the comprehensive nature of these methods and the valuable data they deliver. The entire life-cycle of HCV can now be investigated in a human (and much more relevant) context, without recourse to chimpanzee use. This also includes the testing of new therapies and vaccines. Consequently, there is no sound argument against the changes in public policy that propose a move away from chimpanzee use in US laboratories.     

Key factors influencing ADME properties of therapeutic proteins: A need for ADME characterization in drug discovery and development

Protein therapeutics represent a diverse array of biologics including antibodies, fusion proteins, and therapeutic replacement enzymes. Since their inception, they have revolutionized the treatment of a wide range of diseases including respiratory, vascular, autoimmune, inflammatory, infectious, and neurodegenerative diseases, as well as cancer. While in vivo pharmacokinetic, pharmacodynamic, and efficacy studies are routinely carried out for protein therapeutics, studies that identify key factors governing their absorption, distribution, metabolism, and excretion (ADME) properties have not been fully investigated. Thorough characterization and in-depth study of their ADME properties are critical in order to support drug discovery and development processes for the production of safer and more effective biotherapeutics. In this review, we discuss the main factors affecting the ADME characteristics of these large macromolecular therapies. We also give an overview of the current tools, technologies, and approaches available to investigate key factors that influence the ADME of recombinant biotherapeutic drugs, and demonstrate how ADME studies will facilitate their future development.     

菌寄生真菌的研究进展

菌寄生真菌能寄生在其他真菌并抑制其生长这一特性,在防治病原真菌时显示巨大潜力。综述了近年来菌寄生真菌在寄生过程中的识别、信号传导、侵染机制等方面的研究进展,并讨论菌寄生真菌的应用前景。     

Metabolic pathway engineering in lactic acid bacteria

Lactic acid bacteria (LAB) display a relatively simple carbon and energy metabolism where the sugar source is converted mainly to lactic acid. In Lactococcus lactis metabolic engineering has been very successful in the re-routing of lactococcal pyruvate metabolism to products other than lactic acid. Current metabolic engineering approaches tend to focus on more complex, biosynthetic pathways leading to end-products that generate a health benefit for the consumer (nutraceuticals). Several examples of research on these minor pathways in L. lactis have illustrated the potential of LAB as producers of these metabolites. Whole genome sequencing efforts and corresponding global technologies will have an impact on metabolic engineering in the future.     

Use of the true absorption coefficient as a measure of bioavailability of radiocaesium in ruminants

Limitations of existing methods to describe the bioavailability of dietary radionuclides to ruminants (the transfer coefficient and apparent absorption coefficient) have led to the alternative suggestion of using the true absorption coefficient (A _t). Various approaches to estimatingA _t for radiocaesium, involving the intravenous administration of a second isotope, are presented and discussed with reference to results from studies in which a range of radiocaesium sources were examined in sheep. Although estimates ofA _t differed between the sources, they were reasonably consistent between measurement techniques. Those methods which involved the estimation of endogenous faecal excretion of radiocaesium could be used with previously contaminated animals and did not require continuous administrations of radiocaesium isotopes, but gave unreliable results for sources of low bioavailability. Methods based on estimating the turnover rate of dietary radiocaesium through blood plasma were sufficiently sensitive to measureA _t for the range of sources studied. However, they require previously uncontaminated animals and continuous administration of both isotopes for approximately 7 days. Bioavailability is more effectively measured asA _t than as the transfer or apparent absorption coefficients sinceA _t does not incorporate factors relating to the metabolism of radiocaesium in the tissues of the animal. The results of these studies show that differences in transfer coefficients between sheep and cattle and between sheep of differing ages are not due to variation in absorption across the gut. The potential for applying these approaches to other radioactive elements is discussed.     

Applications of high-throughput ADME in drug discovery

Assessment of physicochemical and pharmacological properties is now conducted at very early stages of drug discovery for the purpose of accelerating the conversion of hits and leads into qualified development candidates. In particular, in vitro absorption, distribution, metabolism and elimination (ADME) assays and in vivo drug metabolism pharmacokinetic (DMPK) studies are being conducted throughout the discovery process, from hit generation through to lead optimization, with the goal of reducing the attrition rate of these potential drug candidates as they progress through development. Because the continuing trend in drug discovery has been to access ADME information earlier and earlier in the discovery process, the need has arisen within the analytical community to introduce faster and better analytical methods to enhance the 'developability' of drug leads. Strategies for streamlined ADME assessment of drug candidates in discovery and pre-clinical development are presented within.     

茶树铝、氟富集研究进展

茶树是铝、氟超富集植物,过量铝、氟累积于叶片严重威胁了人类健康,了解铝、氟在茶树体内的代谢机理对降低茶叶中的铝、氟含量很有必要。本文系统阐述了茶树对铝、氟吸收、转运、累积和解毒的最新研究进展,推测了茶树对铝、氟吸收、转运及解毒的机制,提出了今后茶树铝、氟富集研究的方向。