充分利用Bioperl加速生物信息学的研究

Bioperl是Perl语言专门用于生物信息的工具与函数模块集,是世界各地的Perl开发人员在生物信息学、基因组学以及其他生命科学领域的智能结晶,服务于研究生物学问题的生物学家或计算机专家。通过对Bioperl进行了详细的介绍,并利用几个研究中的应用实例充分说明Bioperl在生物信息学研究中的重要地位。     

Open source tools and toolkits for bioinformatics: significance, and where are we?

This review summarizes important work in open-source bioinformatics software that has occurred over the past couple of years. The survey is intended to illustrate how programs and toolkits whose source code has been developed or released under an Open Source license have changed informatics-heavy areas of life science research. Rather than creating a comprehensive list of all tools developed over the last 2-3 years, we use a few selected projects encompassing toolkit libraries, analysis tools, data analysis environments and interoperability standards to show how freely available and modifiable open-source software can serve as the foundation for building important applications, analysis workflows and resources.     

Storage and retrieval of microarray data and open source microarray database software

Microarray technology has been widely adopted by researchers who use both home-made microarrays and microarrays purchased from commercial vendors. Associated with the adoption of this technology has been a deluge of complex data, both from the microarrays themselves, and also in the form of associated meta data, such as gene annotation information, the properties and treatment of biological samples, and the data transformation and analysis steps taken downstream. In addition, standards for annotation and data exchange have been proposed, and are now being adopted by journals and funding agencies alike. The coupling of large quantities of complex data with extensive and complex standards require all but the most small-scale of microarray users to have access to a robust and scaleable database with various tools. In this review, we discuss some of the desirable properties of such a database, and look at the features of several freely available alternatives.     

The protozoon and the cell: A brief twentieth-century overview

This paper represents the subject matter of an invitational presentation made October 24, 1986, at the meetings of the History of Science Society held in Pittsburgh, Pa. By uncanny coincidence, considering the topics of our papers, that day was also the birthday (the 354th) of the founding father of protozoology, Antony van Leeuwenhoek! Appreciation is expressed here for the support of National Science Foundation grant BSR 83-07113.     

The voyage of stem cell toward terminal differentiation: a brief overview

Presently, worldwide attempts are being made to apply stem cells and stem cell-derived products to a wide range of clinical applications and for the development of cell-based therapies. In order to harness stem cells and manipulate them for therapeutic application, it is very important to understand the basic biology of stem cells and identify the factors that govern the dynamics of these cells in the body. Several signaling pathways have emerged as key regulators of stem cells. Some of these signaling pathways regulate the stem cell's proliferative capacity and therefore act as direct regulators of the stem cell, whereas others are involved in shaping and maintaining the stem cell niche and therefore act as indirect regulators of the stem cell. It is difficult to identify which signaling pathways critically affect the stem cell's behavior and which are important for maintaining the quiescent population. A stem cell receives different extrinsic signals compared with the bulk population and responds to them differently. In order to manipulate these adult cells for therapeutic approaches it is crucial to identify how signaling pathways regulate stem cells either directly by regulating proliferative status or indirectly by influencing the niche. The main challenge is to identify whether different factors provide diverse extrinsic signals to the stem cell and its daughter cell population, or whether there are intrinsic differences in stem cell and daughter cell populations that is reflected in their behavior. In this study, we will focus on the various aspects of stem cell biology and differentiation, as well as exploring the potential strategies to intervene the differentiation process in order to obtain the desired yield of cells applicable in regenerative medicine.     

The stability of ecosystems: A brief overview of the paradox of enrichment

In theory, enrichment of resource in a predator-prey model leads to destabilization of the system,thereby collapsing the trophic interaction,a phenomenon referred to as "the paradox of enrichment". After it was first pro posed by Rosenzweig (1971), a number of subsequent studies were carried out on this dilemma over many decades. In this article, we review these theoretical and experimental works and give a brief overview of the proposed solutions to the paradox. The mechanisms that have been discussed are modifications of simple predator -prey models in the presence of prey that is inedible, invulnerable, unpalatable and toxic. Another class of mechanisms includes an incorporation of a ratio-dependent functional form,inducible defence of prey and density-dependent mortality of the predator. Moreover, we find a third set of explanations based on complex population dynamics including chaos in space and time. We conclude that,although any one of the various mechanisms proposed so far might potentially prevent destabilization of the predator-prey dynamics following enrichment, in nature different mechanisms may combine to cause stability, even when a system is enriched. The exact mechanisms,which may differ among systems,need to be disentangled through extensive field studies and laboratory experiments coupled with realistic theoretical models.     

Side effects of atypical antipsychotics: a brief overview

This paper reviews the available evidence concerning the side effects of atypical antipsychotics, including weight gain, type II diabetes mellitus, hyperlipidemia, QTc interval prolongation, myocarditis, sexual side effects, extrapyramidal side effects and cataract. Some recommendations about how to prevent and manage these side effects are also provided. It is concluded that atypical antipsychotics do not represent a homogeneous class, and that differences in side effects should be taken into account by clinicians when choosing an antipsychotic for an individual patient.     

ExpaRNA-P: simultaneous exact pattern matching and folding of RNAs

Background

Identifying sequence-structure motifs common to two RNAs can speed up the comparison of structural RNAs substantially. The core algorithm of the existent approach ExpaRNA solves this problem for a priori known input structures. However, such structures are rarely known; moreover, predicting them computationally is no rescue, since single sequence structure prediction is highly unreliable.

Results

The novel algorithm ExpaRNA-P computes exactly matching sequence-structure motifs in entire Boltzmann-distributed structure ensembles of two RNAs; thereby we match and fold RNAs simultaneously, analogous to the well-known “simultaneous alignment and folding” of RNAs. While this implies much higher flexibility compared to ExpaRNA, ExpaRNA-P has the same very low complexity (quadratic in time and space), which is enabled by its novel structure ensemble-based sparsification. Furthermore, we devise a generalized chaining algorithm to compute compatible subsets of ExpaRNA-P’s sequence-structure motifs. Resulting in the very fast RNA alignment approach ExpLoc-P, we utilize the best chain as anchor constraints for the sequence-structure alignment tool LocARNA. ExpLoc-P is benchmarked in several variants and versus state-of-the-art approaches. In particular, we formally introduce and evaluate strict and relaxed variants of the problem; the latter makes the approach sensitive to compensatory mutations. Across a benchmark set of typical non-coding RNAs, ExpLoc-P has similar accuracy to LocARNA but is four times faster (in both variants), while it achieves a speed-up over 30-fold for the longest benchmark sequences (≈400nt). Finally, different ExpLoc-P variants enable tailoring of the method to specific application scenarios. ExpaRNA-P and ExpLoc-P are distributed as part of the LocARNA package. The source code is freely available at http://www.bioinf.uni-freiburg.de/Software/ExpaRNA-P.

Conclusions

ExpaRNA-P’s novel ensemble-based sparsification reduces its complexity to quadratic time and space. Thereby, ExpaRNA-P significantly speeds up sequence-structure alignment while maintaining the alignment quality. Different ExpaRNA-P variants support a wide range of applications.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-014-0404-0) contains supplementary material, which is available to authorized users.     

The Bio in Aluminum and Silicon Geochemistry

The translocation and transformation of Al and Si are of paramount importance in the processes of primary-mineral weathering, saprolite formation and soil formation. Geochemical mass balance studies of these processes have often not considered the important role of the biota in cycling of these omnipresent soil elements. In the Calhoun Experimental Forest, SC, we found a mean annual biological uptake of Al and Si of 2.28 and 15.8 kg ha-1 yr-1, respectively, with a mean annual accumulation in aboveground biomass of 0.48 and 2.32 kg ha-1 yr-1, respectively. In the case of Al, net soil leaching from 6 m depth is zero, thus biomass accumulation of Al accounts for the only removal from the soil system. There is an additional internal system mobilization of Al of 6.6 kg ha-1 yr-1, in response to biotic inputs of dissolved organic carbon. In the case of Si, net soil leaching to groundwater is 17.26 kg ha-1 yr-1. The accumulation of Si in aboveground biomass, 2.32 kg ha-1 yr-1, and in forest floor organic matter, 11.95 kg ha-1 yr-1, augments the annual weathering release estimate of Si by an additional 82%. The inclusion of biological cycling of both essential and non-essential mineral elements is important for properly evaluating the biogeochemistry of the earth's crust.     

Structure and evolutionary aspects of matrix metalloproteinases: A brief overview

The matrix metalloproteinases (MMPs) are zinc dependent endopeptidases known for their ability to cleave one or several extracellular matrix (ECM) constituents, as well as non-matrix proteins. They comprise a large family of proteinases that share common structural and functional elements and are products of different genes. All members of this family contain a signal peptide, a propeptide and a catalytic domain. The catalytic domain contains two zinc ions and at least one calcium ion coordinated to various residues. All MMPs, with the exception matrilysin, have a hemopexin/vitronectin-like domain that is connected to the catalytic domain by a hinge or linker region. The hemopexin-like domain influences tissue inhibitor of metalloproteinases (TIMP) binding, the binding of certain substrates, membrane activation, and some proteolytic activities. It has been proposed that the origin of MMPs could be traced to before the emergence of vertebrates from invertebrates. It appears conceivable that the domain assemblies occurred at an early stage of the diversification of different MMPs and that they progressed through the evolutionary process independent of one another, and perhaps parallel to each other.     

Oxovanadium(IV) complexes of carbohydrates: A brief overview

In this brief review the most recent studies and the most relevant aspects of the complexes generated by interaction of carbohydrates and related molecules with the oxovanadium(IV) cation, VO²⁺, are presented and discussed. The survey includes complexes of mono-, di- and polysaccharides, and of other molecules related to simple sugars. First studies with conduritols and related molecules are also described. Moreover, complexes of ascorbic and quinic acids and of some peculiar flavonoids are also included. Some comments on the general physicochemical properties of these complexes are made and their biological activities and effects are also briefly discussed.     

生物信息学方法预测蛋白质相互作用网络中的功能模块

蛋白质相互作用是大多数生命过程的基础。随着高通量实验技术和计算机预测方法的发展,在各种生物中已获得了数目十分庞大的蛋白质相互作用数据,如何从中提取出具有生物学意义的数据是一项艰巨的挑战。从蛋白质相互作用数据出发获得相互作用网络进而预测出其中的功能模块,对于蛋白质功能预测、揭示各种生化反应过程的分子机理都有着极大的帮助。我们分类概括了用生物信息学预测蛋白质相互作用功能模块的方法,以及对这些方法的评价,并介绍了蛋白质相互作用网络比较的一些方法。     

Chemotherapy through mitochondrial apoptosis using nutritional supplements and herbs: A brief overview

There has been increased interest in the use of naturally occurring compounds with chemopreventive and chemotherapeutic effects in the treatment of cancers. This review summarizes the most recent advances that provide new insights into the molecular mechanisms underlying the apoptotic potential of nutritional supplements and herbs. Apoptosis is an essential process in the pathogenesis of cancer and its mechanisms can be subdivided into either a death receptor-dependent extrinsic pathway or an independent (mitochondrial or intrinsic) pathway. Nutritional supplements and herbs can exert their effects on such pathways separately, sequentially, or in a manner of “crosstalk” between pathways. A strong correlation between the early collapse of the mitochondrial membrane potential and apoptosis was found for most nutritional supplements and herbs that have been studied. These observations provide examples of the development of mitochondrial targeting strategies for cancer therapy.     

Transport ATPases in biological systems and relationship to human disease: a brief overview

Interest in the field of transport ATPases has grown dramatically during the past 20 years and gained considerable visibility for several reasons. First, it was shown that most transport ATPases can be lumped into only a few categories designated simply as P, V, F, and ABC types, the latter consisting of a large superfamily. Second, it has been shown that many transport ATPases have a clear relevance to human disease. Third, the field of transport ATPases has become rather advanced in the study of the reaction mechanisms and structure–function relationships associated with several of these enzymes. Finally, the Nobel committee recently recognized major accomplishments in this field of research. Here, the author provides a brief discussion of transport ATPases that are present in biological systems and their relevance or possible relevance to human disease.     

Eicosanoids and their role in immune modulation in fish—a brief overview

Eicosanoids have been demonstrated to play a central role in immune regulation in mammals brought about by their direct effects on cells such as macrophages and lymphocytes or by their indirect effects via cytokines. Studies have shown that fish mononuclear phagocytes, granulocytes and thrombocytes synthesize and release both cyclooxygenase- and lipoxygenase-derived products such as prostaglandin E₂, leukotriene B₄ and lipoxin A₄. Whether lymphocytes have the ability to generate leukotrienes and lipoxins is still unclear but they do appear to have 12-lipoxygenase activity that leads to the generation of 12-hydroxy fatty acid derivatives. As in mammals, leukotriene and lipoxin biosynthesis requires the presence of a 5-lipoxygenase activating protein-like molecule that is sensitive to the action of the specific inhibitor, MK-886. The prostaglandin-generating ability of trout macrophages can be altered by incubation with lipopolysaccharide suggesting the possible presence of an inducible cyclooxygenase activity. Prostaglandins have been found to suppress the mitogen-induced proliferation of trout leucocytes and the generation of humoral antibody and plasma cells both in vivo and in vitro. The lipoxygenase products, leukotriene B₄ and lipoxin A₄ have more variable effects ranging from inhibition to stimulation depending on the assay system employed. Overall, there is clear evidence that eicosanoids play a role in immune regulation in fish in a similar way to that reported in mammals.