A practical guide to molecular dating

Molecular dating has now become a common tool for many biologists and considerable methodological improvements have been made over the last few years. However, the practice of estimating divergence times using molecular data is highly variable among researchers and it is not straightforward for a newcomer to the field to know how to start. Here I provide a brief overview of the current state-of-the-art of molecular dating practice. I review some of the important choices that must be made when conducting a divergence time analysis, including how to select and use calibrations and which relaxed clock model and program to use, with a focus on some practical aspects. I then provide some guidelines for the interpretation of results and briefly review some alternatives to molecular dating for obtaining divergence times. Last, I present some promising developments for the future of the field, related to the improvement of the calibration process.     

Environmental metabolomics: a SWOT analysis (strengths, weaknesses, opportunities, and threats)

Metabolomic approaches have the potential to make an exceptional contribution to understanding how chemicals and other environmental stressors can affect both human and environmental health. However, the application of metabolomics to environmental exposures, although getting underway, has not yet been extensively explored. This review will use a SWOT analysis model to discuss some of the strengths, weaknesses, opportunities, and threats that are apparent to an investigator venturing into this relatively new field. SWOT has been used extensively in business settings to uncover new outlooks and identify problems that would impede progress. The field of environmental metabolomics provides great opportunities for discovery, and this is recognized by a high level of interest in potential applications. However, understanding the biological consequence of environmental exposures can be confounded by inter- and intra-individual differences. Metabolomic profiles can yield a plethora of data, the interpretation of which is complex and still being evaluated and researched. The development of the field will depend on the availability of technologies for data handling and that permit ready access metabolomic databases. Understanding the relevance of metabolomic endpoints to organism health vs adaptation vs variation is an important step in understanding what constitutes a substantive environmental threat. Metabolomic applications in reproductive research are discussed. Overall, the development of a comprehensive mechanistic-based interpretation of metabolomic changes offers the possibility of providing information that will significantly contribute to the protection of human health and the environment.     

Mitochondrial DNA and human evolution

For the past seven years or so, much discussion and controversy in the field of human evolution has revolved around the application and interpretation of studies of human mitochondrial DNA variation, particularly the hypothesis that all mtDNA types in contemporary populations can be traced back to a single African ancestor who lived about 200,000 years ago. In this review I describe the evidence that led to this hypothesis, subsequent work, and where things stand now, particularly with respect to recent criticisms concerning the adequacy of phylogenetic analyses of the mtDNA data. I also describe a new method of analyzing mtDNA data that suggests that all human populations underwent a dramatic expansion some 40,000 years ago, possibly in association with revolutionary advances in human behavior, as well as an important implication of population expansions for mtDNA disease studies.     

Data manipulation and gradient length estimation in DCA ordination

Abstract. The effects of different kinds of data manipulation on gradient length estimation by non-linear rescal-ing (as in DCA ordination) are evaluated by considering the first axis inDCA ordinations of 11 field data sets from four investigations. Gradient length estimates are dependent on the range of the abundance scale; the more the scale favours the quantitative aspect (abundance) of the data over the qualitative aspect (presence), the longer the DCA axes. The gradient length estimate decreases when infrequent species are deleted. A new formula is proposed to replace the option for downweighting of rare species in DCA, as the option presently available has some undesirable properties. Some implications for interpretation of gradient length estimates by non-linear rescaling in general (and in DCA in particular) and for comparison of gradient length estimates between studies, are discussed. The potential of non-linear rescaling of gradients for estimation of β diversity is emphasized.     

Schistosomiasis and malaria: another piece of the crossreactivity puzzle

The recent discovery that individuals living in endemic areas have antibodies in their sera that are crossreactive for both helminth and malaria parasites raises important questions both of the interpretation of existing immunoepidemiological data and of the basic biology of the host and the parasites. One such shared antigen (SmLRR) has now been cloned and has, therefore, opened up an intriguing and exciting field of research for immunologists and parasitologists.     

Age and sex-ratio expression in Drosophila mediopunctata

The sex-ratio trait - production of progenies with excess of females due to X-linked meiotic drive in parental males - has a variable expression in Drosophila mediopunctata. We tested the effect of male age and found that aging increases the expression of sex-ratio, a fact relevant for the interpretation of field data and for experimental design.     

Jaime Alvarez and the case against slow axoplasmic transport: some epistemological reflections.

The 'slow axoplasmic transport theory' has been the prevailing view over the last forty years in order to explain the metabolic maintenance of neuronal axons and nerve endings. A significant amount of evidence against this theoretic interpretation of the existing experimental data has been presented by J. Alvarez, A. Giuditta and E. Koenig in an exhaustive review. They propose an alternative theoretical interpretation called the 'local synthesis model', integrating recent evidence for axon biology and regeneration. We present some epistemological considerations that reinforce the above criticisms and propositions.     

GeneTools – application for functional annotation and statistical hypothesis testing

Background  

Modern biology has shifted from "one gene" approaches to methods for genomic-scale analysis like microarray technology, which allow simultaneous measurement of thousands of genes. This has created a need for tools facilitating interpretation of biological data in "batch" mode. However, such tools often leave the investigator with large volumes of apparently unorganized information. To meet this interpretation challenge, gene-set, or cluster testing has become a popular analytical tool. Many gene-set testing methods and software packages are now available, most of which use a variety of statistical tests to assess the genes in a set for biological information. However, the field is still evolving, and there is a great need for "integrated" solutions.     

Interactome data and databases: different types of protein interaction

In recent years, the biomolecular sciences have been driven forward by overwhelming advances in new biotechnological high-throughput experimental methods and bioinformatic genome-wide computational methods. Such breakthroughs are producing huge amounts of new data that need to be carefully analysed to obtain correct and useful scientific knowledge. One of the fields where this advance has become more intense is the study of the network of 'protein-protein interactions', i.e. the 'interactome'. In this short review we comment on the main data and databases produced in this field in last 5 years. We also present a rationalized scheme of biological definitions that will be useful for a better understanding and interpretation of 'what a protein-protein interaction is' and 'which types of protein-protein interactions are found in a living cell'. Finally, we comment on some assignments of interactome data to defined types of protein interaction and we present a new bioinformatic tool called APIN (Agile Protein Interaction Network browser), which is in development and will be applied to browsing protein interaction databases.     

Bioinformatics

Bioinformatics is an interdisciplinary field that blends computer science and biostatistics with biological and biomedical sciences such as biochemistry, cell biology, developmental biology, genetics, genomics, and physiology. An important goal of bioinformatics is to facilitate the management, analysis, and interpretation of data from biological experiments and observational studies. The goal of this review is to introduce some of the important concepts in bioinformatics that must be considered when planning and executing a modern biological research study. We review database resources as well as data mining software tools.     

Polarized fluorescence in an electric field: steady state and transient values for the fourth moment of the orientation function at arbitrary fields

Steady state and time dependent expressions for the field dependence of the fourth moment of the orientation function at arbitrary fields, which are requested for the interpretation of polarisation of fluorescence in an electric field, have been obtained for permanent and induced dipole orientation. Some general features of the results and some problems connected with their application are pointed out.     

Do dolphins know their own minds?

Knowledge of one's own states of mind is one of the varieties of self-knowledge. Do any nonhuman animals have the capacity for this variety of self-knowledge? The question is open to empirical inquiry, which is most often conducted with primate subjects. Research with a bottlenose dolphin gives some evidence for the capacity in a nonprimate taxon. I describe the research and evaluate the metacognitive interpretation of the dolphin's behaviour. The research exhibits some of the difficulties attached to the task of eliciting behaviour that both attracts a higher-order interpretation while also resisting deflationary, lower-order interpretations. Lloyd Morgan's Canon, which prohibits inflationary interpretations of animal behaviour, has influenced many animal psychologists. There is one defensible version of the Canon, the version that warns specifically against unnecessary intentional ascent. The Canon on this interpretation seems at first to tell against a metacognitive interpretation of the data collected in the dolphin study. However, the model of metacognition that is in play in the dolphin studies is a functional model, one that does not implicate intentional ascent. I explore some interpretations of the dolphin's behaviour as metacognitive, in this sense. While this species of metacognitive interpretation breaks the connection with the more familiar theory of mind research using animal subjects, the interpretation also points in an interesting way towards issues concerning consciousness in dolphins.     

Identifying 5-methylcytosine and related modifications in DNA genomes.

Intense interest in the biological roles of DNA methylation, particularly in eukaryotes, has produced at least eight different methods for identifying 5-methylcytosine and related modifications in DNA genomes. However, the utility of each method depends not only on its simplicity but on its specificity, resolution, sensitivity and potential artifacts. Since these parameters affect the interpretation of data, they should be considered in any application. Therefore, we have outlined the principles and applications of each method, quantitatively evaluated their specificity,resolution and sensitivity, identified potential artifacts and suggested solutions, and discussed a paradox in the distribution of m5C in mammalian genomes that illustrates how methodological limitations can affect interpretation of data. Hopefully, the information and analysis provided here will guide new investigators entering this exciting field.     

Medical images and automated interpretation

The application of automated interpretation to medical images is discussed and the main methods of medical imaging are briefly described. The factors behind the process of human clinical interpretation are also considered. Because human interpretation can be aided by processing of the raw image, the standard methods of image processing are mentioned. Automated interpretation of images in other fields is relevant, and segmentation of images is an important initial part of the process. There are already some applications of automated interpretation of medical images. Some are more complete than others. This will undoubtedly be an important developing field of work which will draw on experience from other areas, and be spurred on by the increasing complexity of medical imaging methods and shortage of expertise for human interpretation.     

Appearance frequency modulated gene set enrichment testing

Background  

Gene set enrichment testing has helped bridge the gap from an individual gene to a systems biology interpretation of microarray data. Although gene sets are defined a priori based on biological knowledge, current methods for gene set enrichment testing treat all genes equal. It is well-known that some genes, such as those responsible for housekeeping functions, appear in many pathways, whereas other genes are more specialized and play a unique role in a single pathway. Drawing inspiration from the field of information retrieval, we have developed and present here an approach to incorporate gene appearance frequency (in KEGG pathways) into two current methods, Gene Set Enrichment Analysis (GSEA) and logistic regression-based LRpath framework, to generate more reproducible and biologically meaningful results.     

On clinical efficacy: why biofeedback does--and does not--work

Questions of clinical efficacy are becoming more prominent in this era of diminishing funds for research and clinical care, and new treatment procedures, in particular, are being rigorously scrutinized. This presents a challenge for the relatively recent field of biofeedback and applied psychophysiology. This field has a strong scientific orientation and a rapidly expanding research base, which includes many well-controlled clinical outcome studies. The point is raised, and illustrated with data from current clinical outcome studies, that it is time for a shift in emphasis away from simply piling study upon study and toward more thoughtful interpretation of experimental and clinical findings and the development of a clearer conceptual framework for biofeedback therapy and research.     

Mechanism of the chain extension step in the biosynthesis of fatty acids

The chain extension step in the enzymatic synthesis of fatty acids by fatty acid synthase, involving a formal Claisen condensation of thio esters, has been clarified by theoretical calculations for model systems, using the modified neglect of diatomic overlap and Austin Model 1 parametric self-consistent field molecular orbital procedures. The reaction involves a free carbanion, formed by decarboxylation of a malonate ion. Formation of the carbanion and condensation with the fatty acid thio ester are not concerted. The decarboxylation is strongly endothermic. It is brought about by electrostatic interaction (field effect) with an ammonium ion derived from an adjacent lysine residue, the ions being far enough apart to inhibit proton transfer between them. Proton transfer would lead to an enol that is predicted not to be able to undergo the Claisen condensation. The formation of the ammonium ion is considered in terms of the pKa of the relevant groups. The bearing of this work on a recent interpretation of the activity and selectivity of enzyme reactions is discussed, and some misunderstandings concerning this interpretation are clarified.     

Paleoprimatological research over the last 50 years: Foci and trends

Since 1930 the approach to fossil primates has undergone a twofold revolution, in more advanced taxonomic thinking, and in the growth of studies relating living primates to the interpretation of past forms. Great strides have also been made in discovering primate fossils–in 1930 there were some 58 genera of extinct primates known, and since then more than 65 new genera have been named. A major aspect of paleoprimatological research today is multidisciplinary field projects, which have accounted for a fuller understanding of dating and context. The application of functional morphology to aspects of primate evolution has allowed better understanding of primate locomotion, diet, and behavior.     

自噬的检测方法及评述

细胞自噬是广泛存在于真核细胞内的一种降解途径,在机体发育过程中、在生理和病理状况下都起重要作用。近年,自噬成为热点研究领域,但少有论文深入分析不同检测方法得来的数据在研究中的不同意义,说明不同检测方法所获的结果的优缺点和适用条件。本文拟对哺乳动物细胞自噬检测方法进行归类、介绍及评述,旨在为研究工作中自噬检测方法的选择和研究结果的解释起帮助作用。