Innovation: Metabolomics: the apogee of the omics trilogy

Metabolites, the chemical entities that are transformed during metabolism, provide a functional readout of cellular biochemistry. With emerging technologies in mass spectrometry, thousands of metabolites can now be quantitatively measured from minimal amounts of biological material, which has thereby enabled systems-level analyses. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanism are being revealed and are shaping our understanding of cell biology, physiology and medicine.     

Focus: Microbiome: Unraveling the Dynamics of the Human Vaginal Microbiome

Four Lactobacillus species, namely L. crispatus, L. iners, L. gasseri, and L. jensenii, commonly dominate the vaginal communities of most reproductive-age women. It is unclear why these particular species, and not others, are so prevalent. Historically, estrogen-induced glycogen production by the vaginal epithelium has been proffered as being key to supporting the proliferation of vaginal lactobacilli. However, the ‘fly in the ointment’ (that has been largely ignored) is that the species of Lactobacillus commonly found in the human vagina cannot directly metabolize glycogen. It would appear that this riddle has been solved as studies have demonstrated that vaginal lactobacilli can metabolize the products of glycogen depolymerization by α-amylase, and fortunately, amylase activity is found in vaginal secretions. These amylases are presumed to be host-derived, but we suggest that other bacterial populations in vaginal communities could also be sources of amylase in addition to (or instead of) the host. Here we briefly review what is known about human vaginal bacterial communities and discuss how glycogen-derived resources and resource competition might shape the composition and structure of these communities.     

Diabetes: the importance of the liver

Insulin resistance, the hallmark of non-insulin dependent diabetes mellitus, is characterized by the failure of tissues to take up and store glucose in response to insulin. Two recent studies shed new light on the importance of insulin signalling in the liver and how this may become defective in diabetes.     

Neuroeconomics: the shadow of the future

Humans and other animals tend to disregard future benefits and costs when choosing between immediate and delayed gratification. This tendency can lead to the choice of options that are not in one's own long-term interest. A new study looks at the neurophysiological basis of this self-defeating behavior.     

Coronins: the return of the crown

Coronins are highly conserved regulators of the actin cytoskeleton whose structure and biological function have remained mysterious until recently. They were originally identified in Dictyostelium, where they localize to actin-rich crown-like structures on the dorsal surface of cells. Coronins bind filamentous actin and the Arp2/3 complex and are involved in modulating actin dynamics. Unlike other known Arp2/3-binding proteins, coronins inhibit Arp2/3 nucleating activity. Genetic data from Dictyostelium, yeast and Drosophila indicate that coronins are important regulators of several actin-dependent physiological processes. Here, we review recent insights into mammalian coronin structure, function and regulation and identify key questions that remain unanswered in this field.     

Water: the bloodstream of the biosphere

Water, the bloodstream of the biosphere, determines the sustainability of living systems. The essential role of water is expanded in a conceptual model of energy dissipation, based on the water balance of whole landscapes. In this model, the underlying role of water phase changes--and their energy-dissipative properties--in the function and the self-organized development of natural systems is explicitly recognized. The energy-dissipating processes regulate the ecological dynamics within the Earth's biosphere, in such a way that the development of natural systems is never allowed to proceed in an undirected or random way. A fundamental characteristic of self-organized development in natural systems is the increasing role of cyclic processes while loss processes are correspondingly reduced. This gives a coincidental increase in system efficiency, which is the basis of growing stability and sustainability. Growing sustainability can be seen as an increase of ecological efficiency, which is applicable at all levels up to whole landscapes. Criteria for necessary changes in society and for the design of the measures that are necessary to restore sustainable landscapes and waters are derived.     

Aging: the sins of the parents

Yeast cells have an asymmetric, stem-cell-like division. As the mother cell ages it becomes 100 times more genetically unstable, but it is only the daughter cells that exhibit loss of heterozygosity; the latter effect is not connected to SIR2-dependent aging, but seems to be accompanied by a loss of the DNA damage checkpoint.     

Mimicry: the hunting of the supergene

Mimicry is an example of an adaptation that requires the integration of several components. Genetic characterisation of a mimicry polymorphism in a butterfly reveals the expected suppression of recombination among its components, preventing the production of unfit character combinations.     

Lizards from the end of the world: phylogenetic relationships of the Liolaemus lineomaculatus section (Squamata: Iguania: Liolaemini)

The Liolaemus lineomaculatus section is a geographically widely distributed group of lizards from the Patagonian region of southern South America, and includes 18 described species representing the most southerly distributed Liolaemus taxa (the genus includes 228 species and extends from Tierra del Fuego north to south-central Peru). Despite high species diversity, the phylogenetic relationships of this section are unknown. In the present work we sampled all described species in the L. lineomaculatus section as well as currently undescribed candidate species to reconstruct the first complete phylogenetic hypothesis for the clade. Our data set included four anonymous nuclear loci, three nuclear protein-coding loci, and two mitochondrial genes. We compared results obtained with three different phylogenetic methods for the concatenated data set (Maximum Parsimony, Maximum Likelihood and Bayesian Inference) with a coalescent-based species tree approach (BEST), and recovered congruent, strongly-supported topological arrangements across all methods. We identified four main clades within the L. lineomaculatus section: the lineomaculatus, magellanicus, somuncurae, and kingii+archeforus groups, for which we estimated divergence times. We discuss the taxonomic implications of these results and how the future integration of phylogeographic, niche modeling and morphological approaches will allow testing biogeographical hypotheses in this clade.     

Focus: The Aging Brain: Palliative Care and the Humanities: Centralizing the Patient at the End of Life

Palliative care is a quickly growing facet of modern medicine. While scientific advancements have broken new ground for the possibilities of end-of-life care, sensitive treatment of the patient as an individual has lagged behind and has frequently led to an unsatisfactory experience for patients, families, and the medical community at large. This essay argues that centralizing patients during the terminal phases of treatment by using humanistic perspectives has the potential to bring new meaning and improved effectiveness to patients and physicians alike.     

Perspective: purging the genetic load: a review of the experimental evidence

Inbreeding depression, the reduction in fitness that accompanies inbreeding, is one of the most important topics of research in evolutionary and conservation genetics. In the recent literature, much attention has been paid to the possibility of purging the genetic load. If inbreeding depression is due to deleterious alleles, whose effect on fitness are negative when in a homozygous state, then successive generations of inbreeding may result in a rebound in fitness due to the selective decrease in frequency of deleterious alleles. Here we examine the experimental evidence for purging of the genetic load by collating empirical tests of rebounds in fitness-related traits with inbreeding in animals and plants. We gathered data from 28 studies including five mammal, three insect, one mollusc, and 13 plant species. We tested for purging by examining three measures of fitness-component variation with serial generations of inbreeding: (1) changes in inbreeding depression, (2) changes in fitness components of inbred lines relative to the original outbred line, and (3) purged population (outcrossed inbred lines) trait means as a function of ancestral outbred trait means. Frequent and substantial purging was found using all three measures, but was particularly pronounced when tracking changes in inbreeding depression. Despite this, we found little correspondence between the three measures of purging within individual studies, indicating that the manner in which a researcher chooses to estimate purging will affect interpretation of the results obtained. The discrepancy suggests an alternative hypothesis: rebounds in fitness with inbreeding may have resulted from adaptation to laboratory conditions and not to purging when using outcrossed inbred lines. However, the pronounced reduction in inbreeding depression for a number of studies provides evidence for purging, as the measure is likely less affected by selection for laboratory conditions. Unlike other taxon-specific reviews on this topic, our results provide support for the purging hypothesis, but firm predictions about the situations in which purging is likely or the magnitude of fitness rebound possible when populations are inbred remain difficult. Further research is required to resolve the discrepancy between the results obtained using different experimental approaches.