Insider information: what viruses tell us about endocytosis

Viruses have long served as tools in molecular and cellular biology to study a variety of complex cellular processes. Currently, there is a revived interest in virus entry into animal cells because it is evident that incoming viruses make use of numerous endocytic pathways that are otherwise difficult to study. Besides the classical clathrin-mediated uptake route, viruses use caveolae-mediated endocytosis, lipid-raft-mediated endocytic pathways, and macropinocytosis. Some of these are subject to regulation, involve novel endocytic organelles, and some of them connect organelles that were previously not known to communicate by membrane traffic.     

Segmentation in behavior and what it can tell us about brain function

Natural human behavior is segmented into action units, functionally related groups of movements with durations of a few seconds. This phenomenon can also be found in nonhuman primates and other mammals. In humans, a similar segmentation can be found in planning, preparatory behavior, perception, and speech. Temporal segmentation may be related to the functioning of short-term memory. Segmentation may thus be a central feature of neuronal integration. Segment length was hitherto thought to be determined by either capacity constraints or temporal factors. Instead we show that segment length depends on the interplay between capacity and temporal factors.     

Death and taxis: what non-mammalian models tell us about sphingosine-1-phosphate

Sphingosine-1-phosphate (S1P) is a signaling molecule that regulates critical events including mammalian cell proliferation, survival, migration and cell-cell interactions. Most of these signals are triggered by engagement of sphingosine-1-phosphate receptors of the Edg family. However, accumulating evidence derived from investigation of non-mammalian models that lack Edg receptors suggests that sphingosine-1-phosphate-like molecules can act through alternative mechanisms and thereby contribute to morphogenesis, development, reproduction and survival. This review provides an overview of sphingosine-1-phosphate metabolism, the isolation of genes in this pathway employing yeast genetics, the evidence for its influence on non-mammalian development, and the pertinence of these findings to human disease.     

Double impact: what sibling data can tell us about the long-term negative effects of parental divorce

Most prior research on the adverse consequences of parental divorce has analyzed only one child per family. As a result, it is not known whether the same divorce affects siblings differently. We address this issue by analyzing paired sibling data from the 1994 General Social Survey (GSS) and 1994 Survey of American Families (SAF). Both seemingly unrelated regressions and random effects models are used to study the effect of family background on offspring's educational attainment and marital stability. Parental divorce adversely affects the educational attainment and the probability of divorce of both children within a sibship; in other words, siblings tend to experience the same divorce the same way. However, family structure of origin only accounts for a trivial portion of the shared variance in offspring's educational attainment and marital stability, so parental divorce is only one of many factors determining how offspring fare. These findings were unchanged when controlling for a number of differences both between and within sibships. Also, the negative effects of parental divorce largely do not vary according to respondent characteristics.     

Small is beautiful: what flies tell us about ERM protein function in development

Actin dynamics is recognized as being a determinant in many developmental processes and pathologies, such as cell polarity, morphogenesis and tumour metastasis. However, how actin interacts with the plasma membrane is poorly understood. Although numerous studies in cell culture point to the crucial role of Ezrin, Radixin and Moesin (ERM) proteins in the actin-membrane link, genetic approaches in mice have not yet revealed their activity during development. Drosophila has recently become an alternative and promising system for the genetic study of ERM protein function. This article focuses on advances made in flies, providing evidence for the evolutionary conservation of functional properties of ERM proteins, in addition to shedding new light on their importance for development.     

Biodiversity, biopiracy and benefits: what allegations of biopiracy tell us about intellectual property

This paper examines the concept of biopiracy, which initially emerged to challenge various aspects of the regime for intellectual property rights (IPR) in living organisms, as well as related aspects pertaining to the ownership and apportioning of benefits from 'genetic resources' derived from the world's biodiversity. This paper proposes that we take the allegation of biopiracy seriously due to the impact it has as an intervention which indexes a number of different, yet interrelated, problematizations of biodiversity, biotechnology and IPR. Using the neem tree case as an example, it describes activists' use of the term as one that involves a deliberate simplification of science and IPR. Additionally, it argues that in so doing, biopiracy is positioned as a touchstone that mobilizes actors and problems, and ultimately generates 'solutions' to the very challenges it creates. The paper will also encourage a view of biopiracy claims that does not always treat them simply as claims of theft, or as a misallocation of benefits, but rather as claims that are designed to raise broader questions about the IPR system itself. It concludes by advocating that, in order to properly understand how to address biopiracy, we must be prepared to move beyond the current narrow readings to develop a more complete picture of the term's influence in challenging how, and by whom, the decisions about what is natural and what is invented come to be made.     

Evaluation of kinetic data: What the numbers tell us about PRMTs

Protein arginine N-methyltransferase (PRMT) kinetic parameters have been catalogued over the past fifteen years for eight of the nine mammalian enzyme family members. Like the majority of methyltransferases, these enzymes employ the highly ubiquitous cofactor S-adenosyl-l-methionine as a co-substrate to methylate arginine residues in peptidic substrates with an approximately 4-μM median K_M. The median values for PRMT turnover number (k_cat) and catalytic efficiency (k_cat/K_M) are 0.0051 s⁻¹ and 708 M⁻¹ s⁻¹, respectively. When comparing PRMT metrics to entries found in the BRENDA database, we find that while PRMTs exhibit high substrate affinity relative to other enzyme-substrate pairs, PRMTs display largely lower k_cat and k_cat/K_M values. We observe that kinetic parameters for PRMTs and arginine demethylase activity from dual-functioning lysine demethylases are statistically similar, paralleling what the broader enzyme families in which they belong reveal, and adding to the evidence in support of arginine methylation reversibility.     

The centipede Strigamia maritima: what it can tell us about the development and evolution of segmentation

One of the most fundamental features of the body plan of arthropods is its segmental design. There is considerable variation in segment number among arthropod groups (about 20-fold); yet, paradoxically, the vast majority of arthropod species have a fixed number of segments, thus providing no variation in this character for natural selection to act upon. However, the 1000-species-strong centipede order Geophilomorpha provides an exception to the general rule of intraspecific invariance in segment number. Members of this group, and especially our favourite animal Strigamia maritima, may thus help us to understand the evolution of segment number in arthropods. Evolution must act by modifying the formation of segments during embryogenesis. So, how this developmental process operates, in a variable-segment-number species, is of considerable interest. Strigamia maritima turns out to be a tractable system both at the ecological level of investigating differences in mean segment number between populations and at the molecular level of studying the expression patterns of developmental genes. Here we report the current state of play in our work on this fascinating animal, including our recent finding of a double-segment periodicity in the expression of two Strigamia segmentation genes, and its possible implications for our understanding of arthropod segmentation mechanisms in general.     

Microbial co-habitation and lateral gene transfer: what transposases can tell us

Background

Determining the habitat range for various microbes is not a simple, straightforward matter, as habitats interlace, microbes move between habitats, and microbial communities change over time. In this study, we explore an approach using the history of lateral gene transfer recorded in microbial genomes to begin to answer two key questions: where have you been and who have you been with?

Results

All currently sequenced microbial genomes were surveyed to identify pairs of taxa that share a transposase that is likely to have been acquired through lateral gene transfer. A microbial interaction network including almost 800 organisms was then derived from these connections. Although the majority of the connections are between closely related organisms with the same or overlapping habitat assignments, numerous examples were found of cross-habitat and cross-phylum connections.

Conclusions

We present a large-scale study of the distributions of transposases across phylogeny and habitat, and find a significant correlation between habitat and transposase connections. We observed cases where phylogenetic boundaries are traversed, especially when organisms share habitats; this suggests that the potential exists for genetic material to move laterally between diverse groups via bridging connections. The results presented here also suggest that the complex dynamics of microbial ecology may be traceable in the microbial genomes.     

The settlement of Madagascar: what dialects and languages can tell us

The dialects of Madagascar belong to the Greater Barito East group of the Austronesian family and it is widely accepted that the Island was colonized by Indonesian sailors after a maritime trek that probably took place around 650 CE. The language most closely related to Malagasy dialects is Maanyan, but Malay is also strongly related especially for navigation terms. Since the Maanyan Dayaks live along the Barito river in Kalimantan (Borneo) and they do not possess the necessary skill for long maritime navigation, they were probably brought as subordinates by Malay sailors. In a recent paper we compared 23 different Malagasy dialects in order to determine the time and the landing area of the first colonization. In this research we use new data and new methods to confirm that the landing took place on the south-east coast of the Island. Furthermore, we are able to state here that colonization probably consisted of a single founding event rather than multiple settlements. To reach our goal we find out the internal kinship relations among all the 23 Malagasy dialects and we also find out the relations of the 23 dialects to Malay and Maanyan. The method used is an automated version of the lexicostatistic approach. The data from Madagascar were collected by the author at the beginning of 2010 and consist of Swadesh lists of 200 items for 23 dialects covering all areas of the Island. The lists for Maanyan and Malay were obtained from a published dataset integrated with the author's interviews.     

Inactivation and activity of cholesterol-dependent cytolysins: what structural studies tell us

The homologous bacterially expressed cholesterol-dependent cytolysins (CDCs) form pores via oligomerization; this must occur preferentially once the target membrane has been engaged. Conformational changes in CDCs then drive partition from an aqueous environment to a lipidic one. This review addresses how premature oligomerization is prevented, how conformational changes are triggered, and how cooperativity between subunits brings about new functionality absent from isolated protomers. Variations are found in the answers provided by the CDCs to these issues. Some toxins use pH as a trigger of activity, but recent results have shown that dimerization in solution is an alternative way of preventing premature oligomerization, in particular for the CDC from Clostridium perfringens, perfringolysin. More controversially, there is still no resolution to the debate as to whether incomplete (arciform) oligomers form pores: recent results again suggest that they do.     

Animals models of MCH function and what they can tell us about its role in energy balance

Melanin-concentrating hormone (MCH) has attracted considerable attention because of its effects on food intake and body weight and the MCH receptor (MCHR1) remains one of the viable targets for obesity therapy. This review summarizes the literature examining the effects of MCH on body weight, food intake and energy expenditure in rodent models, and the central sites where MCH acts in regulating energy homeostasis. Emphasis is given on the discrepancies between the genetic and pharmacologic models of MCHR1 inactivation. We propose some solutions to resolve these discrepancies and discuss some future directions in MCH research.     

Social stress models in depression research: what do they tell us?

Interest has recently surged in the use of social stress models, especially social defeat. Such interest lies both in the recognition that stressors of social origin play a major role in human psychopathologies and in the acknowledgement that natural and hence ethologically-based stress models have important translational value. The use of the most recent technology has allowed the recognition of the mechanisms through which social defeat might have enduring psychoneuroendocrine effects, especially social avoidance and anhedonia, two behaviours relevant to human depression. In view of the sensitivity of these behavioural outcomes to repeated antidepressant treatments, the social defeat model has been proposed as a possible animal model of depression. The present survey is aimed at examining the limits of such an interpretation and focuses on methodological aspects and on the relevance of social defeat to the study of anxiety-related pathologies.     

Strategies for determining kinship in wild populations using genetic data

Knowledge of kin relationships between members of wild animal populations has broad application in ecology and evolution research by allowing the investigation of dispersal dynamics, mating systems, inbreeding avoidance, kin recognition, and kin selection as well as aiding the management of endangered populations. However, the assessment of kinship among members of wild animal populations is difficult in the absence of detailed multigenerational pedigrees. Here, we first review the distinction between genetic relatedness and kinship derived from pedigrees and how this makes the identification of kin using genetic data inherently challenging. We then describe useful approaches to kinship classification, such as parentage analysis and sibship reconstruction, and explain how the combined use of marker systems with biparental and uniparental inheritance, demographic information, likelihood analyses, relatedness coefficients, and estimation of misclassification rates can yield reliable classifications of kinship in groups with complex kin structures. We outline alternative approaches for cases in which explicit knowledge of dyadic kinship is not necessary, but indirect inferences about kinship on a group‐ or population‐wide scale suffice, such as whether more highly related dyads are in closer spatial proximity. Although analysis of highly variable microsatellite loci is still the dominant approach for studies on wild populations, we describe how the long‐awaited use of large‐scale single‐nucleotide polymorphism and sequencing data derived from noninvasive low‐quality samples may eventually lead to highly accurate assessments of varying degrees of kinship in wild populations.     

Pedigrees and microsatellites among endangered ungulates: what do they tell us?

Relationships between pedigree coefficients of inbreeding and molecular metrics are generally weak, suggesting that measures of heterozygosity estimated using microsatellites may be poor surrogates of genome-wide inbreeding. We compare three endangered species of gazelles ( Gazella ) with different degrees of threat in their natural habitats, for which captive breeding programmes exist. For G. dorcas, the species with the largest founding population, the highest and most recent number of founding events, the correlation between pedigree coefficient of inbreeding and molecular metrics was higher than for outbred populations of mammals, probably because it has both higher mean f and variance. For the two species with smaller founding populations, conventional assumptions about founders, i.e. outbred and unrelated, are unrealistic. When realistic assumptions about the founders were made, clear relationships between pedigree coefficients of inbreeding and molecular metrics were revealed for G. cuvieri. This population had a small founding population, but it did experience admixture years later; thus, the relationship between inbreeding and molecular metrics in G. cuvieri is very similar to the expected values but lower than in G. dorcas . In contrast, no relationship was found for G. dama mhorr which had a much smaller founding population than had been previously assumed, which probably had high levels of inbreeding and low levels of genetic variability, and no admixture. In conclusion, the strength of the association between pedigree coefficient of inbreeding and molecular metrics among endangered species depends on the level of inbreeding and genetic variability present in the founding population, its size and its history.