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.     

Computational carbohydrate chemistry: what theoretical methods can tell us

Computational methods have had a long history of application to carbohydrate systems and their development in this regard is discussed. The conformational analysis of carbohydrates differs in several ways from that of other biomolecules. Many glycans appear to exhibit numerous conformations coexisting in solution at room temperature and a conformational analysis of a carbohydrate must address both spatial and temporal properties. When solution nuclear magnetic resonance data are used for comparison, the simulation must give rise to ensemble-averaged properties. In contrast, when comparing to experimental data obtained from crystal structures a simulation of a crystal lattice, rather than of an isolated molecule, is appropriate. Molecular dynamics simulations are well suited for such condensed phase modeling. Interactions between carbohydrates and other biological macromolecules are also amenable to computational approaches. Having obtained a three-dimensional structure of the receptor protein, it is possible to model with accuracy the conformation of the carbohydrate in the complex. An example of the application of free energy perturbation simulations to the prediction of carbohydrate-protein binding energies is presented.     

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.     

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.     

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.     

Epithelial cell polarity: what flies can teach us about cancer

Epithelial cells are polarized along their apical-basal axis. Much of the cellular machinery that goes into establishing and maintaining epithelial cell polarity is evolutionarily conserved. Model organisms, including the fruit fly, Drosophila melanogaster, are thus particularly useful for the study of cell polarity. Work in Drosophila has identified several important components of the polarity machinery and has also established the surprising existence of a secondary cell polarity pathway required only under conditions of energetic stress. This work has important implications for the understanding of human cancer. Most cancers are epithelial in origin, and the loss of cell polarity is a critical step towards malignancy. Thus a better understanding of how polarity is established and maintained in epithelial cells will help us to understand the process of malignant transformation and may lead to improved therapies. In the present chapter we discuss the current understanding of how epithelial cell polarity is regulated and the known associations between polarity factors and cancer.     

Gene flow in wild chimpanzee populations: what genetic data tell us about chimpanzee movement over space and time

The isolation of phylogenetically distinct primate immunodeficiency viruses from at least seven wild-born, captive chimpanzees indicates that viruses closely related to HIV-1 may be endemic in some wild chimpanzee populations. The search for the chimpanzee population or populations harbouring these viruses is therefore on. This paper attempts to answer the question of whether or not such populations of chimpanzees are likely to exist at all, and, if so, where they are likely to be found. We summarize what is known about gene flow in wild populations of chimpanzees, both between major phylogeographical subdivisions of the species, and within these subdivisions. Our analysis indicates that hitherto undocumented reproductively isolated chimpanzee populations may in fact exist. This conclusion is based on the observation that, despite limited geographical sampling and limited numbers of genetic loci, conventional notions of the nature and extent of chimpanzee gene flow have recently been substantially revised. Molecular genetic studies using mitochondrial DNA sequences and hypervariable nuclear microsatellite markers have indicated the existence of heretofore undocumented barriers to chimpanzee gene flow. These studies have identified at least one population of chimpanzees genetically distinct enough to be classified into a new subspecies (Pan troglodytes vellerosus). At the same time, they have called into question the long-accepted genetic distinction between eastern chimpanzees (Pan troglodytes schweinfurthii) and western equatorial chimpanzees (Pan troglodytes troglodytes). The same studies have further indicated that gene flow between local populations is more extensive than was previously thought, and follows patterns sometimes inconsistent with those documented through direct behavioural observation. Given the apparently incomplete nature of the current understanding of chimpanzee gene flow in equatorial Africa, it seems reasonable to speculate that a chimpanzee population or populations may exist which both harbour the putative HIV-1 ancestor, and which have remained reproductively isolated from other chimpanzee populations over the time-scale relevant to the evolution of the SIVcpz-HIV-1 complex of viruses. Continued extensive sampling of wild chimpanzee populations, both for their genes and their viruses, should be performed quickly considering the high probability of extinction that many wild chimpanzee populations face today. The history of human-chimpanzee contacts is discussed.     

What blindness can tell us about seeing again: merging neuroplasticity and neuroprostheses

Significant progress has been made in the development of visual neuroprostheses to restore vision in blind individuals. Appropriate delivery of electrical stimulation to intact visual structures can evoke patterned sensations of light in those who have been blind for many years. However, success in developing functional visual prostheses requires an understanding of how to communicate effectively with the visually deprived brain in order to merge what is perceived visually with what is generated electrically.     

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.     

What spectroscopy can still tell us about the secondary structure of bacteriorhodopsin.

The recently published model of the structure of bacteriorhodopsin (bR), developed by fitting the peptide chain to a high-resolution, three-dimensional density map, rules out the existence of transmembrane beta-sheet and provides an accurate estimate of the helix content. The precise geometry of the dihedral angles in the helical regions of the polypeptide cannot yet be specified from the diffraction data, however. Published data on the circular dichroism (CD) spectrum between 190 and 240 nm, and the infrared (IR) spectrum in the amide I band suggest that the helical conformation in bR may be, for the most part, a rather unusual one. The precise structural model, which specifies the number of residues in transmembrane helices, can now be used as an additional constraint in seeking models of the helical conformation that are in quantitative agreement with the CD and IR spectroscopic data. Further spectroscopic measurements can also be used to determine whether there are changes in the unusual dihedral-angle conformation within the helices during the photocycle.     

What mirror self-recognition in nonhumans can tell us about aspects of self

Research on mirror self-recognition where animals are observed for mirror-guided self-directed behaviour has predominated the empirical approach to self-awareness in nonhuman primates. The ability to direct behaviour to previously unseen parts of the body such as the inside of the mouth, or grooming the eye by aid of mirrors has been interpreted as recognition of self and evidence of a self-concept. Three decades of research has revealed that contrary to monkeys, most great apes (humans, common chimpanzees, pygmy chimpanzees and orangutans but not the gorilla) have convincingly displayed the capacity to recognize self by mirrors. The putative discontinuity in phylogeny of the ability suggests the existence of a so-called cognitive gap between great apes and the rest of the animal kingdom. However, methodological and theoretical inconsistencies regarding the empirical approach prevail. For instance, the observation of self-directed behaviour might not be as straightforward as it seems. In addition, the interpretation of mirror self-recognition as an index of self-awareness is challenged by alternative explanations, raising doubt about some assumptions behind mirror self-recognition. To evaluate the significance of the test in discussions of the concept of self this paper presents and analyses some major arguments raised on the mirror task.     

The model student: what chemical model systems can teach us about biology

Model systems have evolved with the times, making use of modern biological methods and incorporating biological complexity. This evolution has increased the relevance of models as tools for studying biology.     

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.     

Targeted disruption of caspase genes in mice: what they tell us about the functions of individual caspases in apoptosis

Cysteine proteases of the caspase family are crucial mediators of apoptosis. All mammalian cells contain a large number of caspases. Although many caspases are activated in a cell committed to apoptosis, recent data from caspase gene knockout mice suggest that individual caspases may be involved in the cell and stimulus-specific pathways of cell death. The gene disruption studies also establish the functional hierarchy between two structurally distinct classes of caspases. The present review discusses these recent findings and elaborates on how these mutant mouse models have helped the understanding of the mechanisms that govern programmed cell death in the immune and other systems.     

What can disulfide bonds tell us about protein energetics, function and folding: simulations and bioninformatics analysis

We study the impact of disulfide bonds on protein stability and folding. Using lattice model simulations, we show that formation of a disulfide bond stabilizes a protein to an extent that depends on the distance along the chain between linked cysteine residues. However, the impact of disulfide bonds on folding kinetics varies broadly, from acceleration when disulfides are introduced in or close to the folding nucleus, to slowing when disulfides are introduced outside the nucleus. Having established the effect of disulfide bonds on stability, we study the correlation between the number of disulfide bonds and the composition of certain amino acid classes with the goal to use it as a statistical probe into factors that contribute to stability of proteins. We find that the number of disulfides is negatively correlated with aliphatic hydrophobic but not aromatic content. It is surprising that we observe a strong correlation of disulfide content with polar (Q,S,T,N) amino acid content and a strong negative correlation with charged (E,D,K,R) content. These findings provide insights into factors that determine protein stability and principles of protein design as well as possible relations of disulfide bonds and protein function.