Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair

Heart disease is a leading cause of death in newborn children and in adults. Efforts to promote cardiac repair through the use of stem cells hold promise but typically involve isolation and introduction of progenitor cells. Here, we show that the G-actin sequestering peptide thymosin beta4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in postnatal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in culture was also enhanced by thymosin beta4. We found that thymosin beta4 formed a functional complex with PINCH and integrin-linked kinase (ILK), resulting in activation of the survival kinase Akt (also known as protein kinase B). After coronary artery ligation in mice, thymosin beta4 treatment resulted in upregulation of ILK and Akt activity in the heart, enhanced early myocyte survival and improved cardiac function. These findings suggest that thymosin beta4 promotes cardiomyocyte migration, survival and repair and the pathway it regulates may be a new therapeutic target in the setting of acute myocardial damage.     

Evolution: how do characters evolve?

Ricklefs claims to show that morphological evolution in birds is associated with speciation events--that is, it is punctuational--by inference from data on only species number, clade age and character variance from a range of passerine clades. He suggests that variance increases in proportion with clade age under gradual change, but in proportion to the logarithm of species number if change is punctuational. Here I show that both clade age and the logarithm of species number independently predict variance under both gradual and punctuational change, rendering Ricklefs' results uninformative about his central hypothesis.     

Small area population estimates project: data quality of administrative datasets

The Office for National Statistics (ONS) has set up a project to investigate the feasibility of producing postcensal small area population estimates on a nationally consistent basis for England and Wales. Research has taken place to identify datasets that could potentially be used within a method to produce small area population estimates. Following an evaluation of a number of different administrative datasets, the most suitable have been short-listed for further consideration. This article presents the findings of the evaluation, based on 2001 data, and summarises the characteristics of these short-listed data sources. This article does not cover the methods that are being evaluated as part of the feasibility assessment.     

Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis

Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are disorders characterized by increased bone density. The occurrence of one or more of these phenotypes in the same individual or family suggests that these entities might be allelic. We collected data from three families in which affected individuals had osteopoikilosis with or without manifestations of BOS or melorheostosis. A genome-wide linkage analysis in these families, followed by the identification of a microdeletion in an unrelated individual with these diseases, allowed us to map the gene that is mutated in osteopoikilosis. All the affected individuals that we investigated were heterozygous with respect to a loss-of-function mutation in LEMD3 (also called MAN1), which encodes an inner nuclear membrane protein. A somatic mutation in the second allele of LEMD3 could not be identified in fibroblasts from affected skin of an individual with BOS and an individual with melorheostosis. XMAN1, the Xenopus laevis ortholog, antagonizes BMP signaling during embryogenesis. In this study, LEMD3 interacted with BMP and activin-TGFbeta receptor-activated Smads and antagonized both signaling pathways in human cells.     

Duplicate genes increase gene expression diversity within and between species

Using microarray gene expression data from several Drosophila species and strains, we show that duplicated genes, compared with single-copy genes, significantly increase gene expression diversity during development. We show further that duplicate genes tend to cause expression divergences between Drosophila species (or strains) to evolve faster than do single-copy genes. This conclusion is also supported by data from different yeast strains.     

Identification of genes involved in Drosophila melanogaster geotaxis,a complex behavioral trait

Identifying the genes involved in polygenic traits has been difficult. In the 1950s and 1960s, laboratory selection experiments for extreme geotaxic behavior in fruit flies established for the first time that a complex behavioral trait has a genetic basis. But the specific genes responsible for the behavior have never been identified using this classical model. To identify the individual genes involved in geotaxic response, we used cDNA microarrays to identify candidate genes and assessed fly lines mutant in these genes for behavioral confirmation. We have thus determined the identities of several genes that contribute to the complex, polygenic behavior of geotaxis.     

Chromatic sensitivity of ganglion cells in the peripheral primate retina

Visual abilities change over the visual field. For example, our ability to detect movement is better in peripheral vision than in foveal vision, but colour discrimination is markedly worse. The deterioration of colour vision has been attributed to reduced colour specificity in cells of the midget, parvocellular (PC) visual pathway in the peripheral retina. We have measured the colour specificity (red-green chromatic modulation sensitivity) of PC cells at eccentricities between 20 and 50 degrees in the macaque retina. Here we show that most peripheral PC cells have red-green modulation sensitivity close to that of foveal PC cells. This result is incompatible with the view that PC pathway cells in peripheral retina make indiscriminate connections ('random wiring') with retinal circuits devoted to different spectral types of cone photoreceptors. We show that selective cone connections can be maintained by dendritic field anisotropy, consistent with the morphology of PC cell dendritic fields in peripheral retina. Our results also imply that postretinal mechanisms contribute to the psychophysically demonstrated deterioration of colour discrimination in the peripheral visual field.     

Understanding the thermal evolution of deep-water continental margins

Areas of exploration for new hydrocarbons are changing as the hydrocarbon industry seeks new resources for economic and political reasons. Attention has turned from easily accessible onshore regions such as the Middle East to offshore continental shelves. Over the past ten years, there has been a marked shift towards deep-water continental margins (500-2,500 m below sea level). In these more hostile regions, the risk and cost of exploration is higher, but the prize is potentially enormous. The key to these endeavours is a quantitative understanding of the structure and evolution of the thinned crust and lithosphere that underlie these margins.