Origami: Single-cell 3D shape dynamics oriented along the apico-basal axis of folding epithelia from fluorescence microscopy data

A common feature of morphogenesis is the formation of three-dimensional structures from the folding of two-dimensional epithelial sheets, aided by cell shape changes at the cellular-level. Changes in cell shape must be studied in the context of cell-polarised biomechanical processes within the epithelial sheet. In epithelia with highly curved surfaces, finding single-cell alignment along a biological axis can be difficult to automate in silico. We present ‘Origami’, a MATLAB-based image analysis pipeline to compute direction-variant cell shape features along the epithelial apico-basal axis. Our automated method accurately computed direction vectors denoting the apico-basal axis in regions with opposing curvature in synthetic epithelia and fluorescence images of zebrafish embryos. As proof of concept, we identified different cell shape signatures in the developing zebrafish inner ear, where the epithelium deforms in opposite orientations to form different structures. Origami is designed to be user-friendly and is generally applicable to fluorescence images of curved epithelia

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Both habitat change and local lek structure influence patterns of spatial loss and recovery in a black grouse population

The final publication is available at Springer via http://dx.doi.org/10.1007/s10144-015-0484-3Land use change is a major driver of declines in wildlife populations. Where human economic or recreational interests and wildlife share landscapes this problem is exacerbated. Changes in UK black grouse Tetrao tetrix populations are thought to have been strongly influenced by upland land use change. In a long-studied population within Perthshire, lek persistence is positively correlated with lek size, and remaining leks clustered most strongly within the landscape when the population is lowest, suggesting that there may be a demographic and/or spatial context to the reaction of the population to habitat changes. Hierarchical cluster analysis of lek locations revealed that patterns of lek occupancy when the population was declining were different to those during the later recovery period. Response curves from lek-habitat models developed using MaxEnt for periods with a declining population, low population, and recovering population were consistent across years for most habitat measures. We found evidence linking lek persistence with habitat quality changes and more leks which appeared between 1994 and 2008 were in improving habitat than those which disappeared during the same period. Generalised additive models (GAMs) identified changes in woodland and starting lek size as being important indicators of lek survival between declining and low/recovery periods. There may also have been a role for local densities in explaining recovery since the population low point. Persistence of black grouse leks was influenced by habitat, but changes in this alone did not fully account for black grouse declines. Even when surrounded by good quality habitat, leks can be susceptible to extirpation due to isolation

Diffusion and perfusion weighted magnetic resonance imaging for tumor volume definition in radiotherapy of brain tumors

Abstract Accurate target volume delineation is crucial for the radiotherapy of tumors. Diffusion and perfusion magnetic resonance imaging (MRI) can provide functional information about brain tumors, and they are able to detect tumor volume and physiological changes beyond the lesions shown on conventional MRI. This review examines recent studies that utilized diffusion and perfusion MRI for tumor volume definition in radiotherapy of brain tumors, and it presents the opportunities and challenges in the integration of multimodal functional MRI into clinical practice. The results indicate that specialized and robust post-processing algorithms and tools are needed for the precise alignment of targets on the images, and comprehensive validations with more clinical data are important for the improvement of the correlation between histopathologic results and MRI parameter images

Sex Promotes Spatial and Dietary Segregation in a Migratory Shorebird during the Non-Breeding Season

Several expressions of sexual segregation have been described in animals, especially in those exhibiting conspicuous dimorphism. Outside the breeding season, segregation has been mostly attributed to size or age-mediated dominance or to trophic niche divergence. Regardless of the recognized implications for population dynamics, the ecological causes and consequences of sexual segregation are still poorly understood. We investigate the foraging habits of a shorebird showing reversed sexual dimorphism, the black-tailed godwit Limosa limosa, during the winter season, and found extensive segregation between sexes in spatial distribution, microhabitat use and dietary composition. Males and females exhibited high site-fidelity but differed in their distributions at estuary-scale. Male godwits (shorter-billed) foraged more frequently in exposed mudflats than in patches with higher water levels, and consumed more bivalves and gastropods and fewer polychaetes than females. Females tended to be more frequently involved and to win more aggressive interactions than males. However, the number of aggressions recorded was low, suggesting that sexual dominance plays a lesser role in segregation, although its importance cannot be ruled out. Dimorphism in the feeding apparatus has been used to explain sex differences in foraging ecology and behaviour of many avian species, but few studies confirmed that morphologic characteristics drive individual differences within each sex. We found a relationship between resource use and bill size when pooling data from males and females. However, this relationship did not hold for either sex separately, suggesting that differences in foraging habits of godwits are primarily a function of sex, rather than bill size. Hence, the exact mechanisms through which this segregation operates are still unknown. The recorded differences in spatial distribution and resource use might expose male and female to distinct threats, thus affecting population dynamics through differential mortality. Therefore, population models and effective conservation strategies should increasingly take sex-specific requirements into consideration

Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.Peer reviewe

From staff-mix to skill-mix and beyond: towards a systemic approach to health workforce management

Throughout the world, countries are experiencing shortages of health care workers. Policy-makers and system managers have developed a range of methods and initiatives to optimise the available workforce and achieve the right number and mix of personnel needed to provide high-quality care. Our literature review found that such initiatives often focus more on staff types than on staff members' skills and the effective use of those skills. Our review describes evidence about the benefits and pitfalls of current approaches to human resources optimisation in health care. We conclude that in order to use human resources most effectively, health care organisations must consider a more systemic approach - one that accounts for factors beyond narrowly defined human resources management practices and includes organisational and institutional conditions

Downregulation of histone H2A and H2B pathways is associated with anthracycline sensitivity in breast cancer

Abstract Background Drug resistance in breast cancer is the major obstacle to effective treatment with chemotherapy. While upregulation of multidrug resistance genes is an important component of drug resistance mechanisms in vitro, their clinical relevance remains to be determined. Therefore, identifying pathways that could be targeted in the clinic to eliminate anthracycline-resistant breast cancer remains a major challenge. Methods We generated paired native and epirubicin-resistant MDA-MB-231, MCF7, SKBR3 and ZR-75-1 epirubicin-resistant breast cancer cell lines to identify pathways contributing to anthracycline resistance. Native cell lines were exposed to increasing concentrations of epirubicin until resistant cells were generated. To identify mechanisms driving epirubicin resistance, we used a complementary approach including gene expression analyses to identify molecular pathways involved in resistance, and small-molecule inhibitors to reverse resistance. In addition, we tested its clinical relevance in a BR9601 adjuvant clinical trial. Results Characterisation of epirubicin-resistant cells revealed that they were cross-resistant to doxorubicin and SN-38 and had alterations in apoptosis and cell-cycle profiles. Gene expression analysis identified deregulation of histone H2A and H2B genes in all four cell lines. Histone deacetylase small-molecule inhibitors reversed resistance and were cytotoxic for epirubicin-resistant cell lines, confirming that histone pathways are associated with epirubicin resistance. Gene expression of a novel 18-gene histone pathway module analysis of the BR9601 adjuvant clinical trial revealed that patients with low expression of the 18-gene histone module benefited from anthracycline treatment more than those with high expression (hazard ratio 0.35, 95 % confidence interval 0.13–0.96, p = 0.042). Conclusions This study revealed a key pathway that contributes to anthracycline resistance and established model systems for investigating drug resistance in all four major breast cancer subtypes. As the histone modification can be targeted with small-molecule inhibitors, it represents a possible means of reversing clinical anthracycline resistance. Trial registration ClinicalTrials.gov identifier NCT00003012 . Registered on 1 November 1999