Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders.

Genes for autism spectrum disorders (ASDs) are also implicated in fragile X syndrome (FXS), intellectual disabilities (ID) or schizophrenia (SCZ), and converge on neuronal function and differentiation. The SH-SY5Y neuroblastoma cell line, the most widely used system to study neurodevelopment, is currently discussed for its applicability to model cortical development. We implemented an optimal neuronal differentiation protocol of this system and evaluated neurodevelopment at the transcriptomic level using the CoNTeXT framework, a machine-learning algorithm based on human post-mortem brain data estimating developmental stage and regional identity of transcriptomic signatures. Our improved model in contrast to currently used SH-SY5Y models does capture early neurodevelopmental processes with high fidelity. We applied regression modelling, dynamic time warping analysis, parallel independent component analysis and weighted gene co-expression network analysis to identify activated gene sets and networks. Finally, we tested and compared these sets for enrichment of risk genes for neuropsychiatric disorders. We confirm a significant overlap of genes implicated in ASD with FXS, ID and SCZ. However, counterintuitive to this observation, we report that risk genes affect pathways specific for each disorder during early neurodevelopment. Genes implicated in ASD, ID, FXS and SCZ were enriched among the positive regulators, but only ID-implicated genes were also negative regulators of neuronal differentiation. ASD and ID genes were involved in dendritic branching modules, but only ASD risk genes were implicated in histone modification or axonal guidance. Only ID genes were over-represented among cell cycle modules. We conclude that the underlying signatures are disorder-specific and that the shared genetic architecture results in overlaps across disorders such as ID in ASD. Thus, adding developmental network context to genetic analyses will aid differentiating the pathophysiology of neuropsychiatric disorders

Sex chromosome and autosome divergence in Podisma (Orthoptera) in western Europe

International audienc

Hydrodynamic modelling of protein conformation in solution: ELLIPS and HYDRO

The last three decades has seen some important advances in our ability to represent the conformation of proteins in solution on the basis of hydrodynamic measurements. Advances in theoretical modeling capabilities have been matched by commensurate advances in the precision of hydrodynamic measurements. We consider the advances in whole-body (simple ellipsoid-based) modeling—still useful for providing an overall idea of molecular shape, particularly for those systems where only a limited amount of data is available—and outline the ELLIPS suite of algorithms which facilitates the use of this approach. We then focus on bead modeling strategies, particularly the surface or shell–bead approaches and the HYDRO suite of algorithms. We demonstrate how these are providing great insights into complex issues such as the conformation of immunoglobulins and other multi-domain complexes

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com

Education and wealth inequalities in healthy ageing in eight harmonised cohorts in the ATHLOS consortium: a population-based study

Background: The rapid growth of the size of the older population is having a substantial effect on health and social care services in many societies across the world. Maintaining health and functioning in older age is a key public health issue but few studies have examined factors associated with inequalities in trajectories of health and functioning across countries. The aim of this study was to investigate trajectories of healthy ageing in older men and women (aged ≥45 years) and the effect of education and wealth on these trajectories. Methods: This population-based study is based on eight longitudinal cohorts from Australia, the USA, Japan, South Korea, Mexico, and Europe harmonised by the EU Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. We selected these studies from the repository of 17 ageing studies in the ATHLOS consortium because they reported at least three waves of collected data. We used multilevel modelling to investigate the effect of education and wealth on trajectories of healthy ageing scores, which incorporated 41 items of physical and cognitive functioning with a range between 0 (poor) and 100 (good), after adjustment for age, sex, and cohort study. Findings: We used data from 141 214 participants, with a mean age of 62·9 years (SD 10·1) and an age range of 45–106 years, of whom 76 484 (54·2%) were women. The earliest year of baseline data was 1992 and the most recent last follow-up year was 2015. Education and wealth affected baseline scores of healthy ageing but had little effect on the rate of decrease in healthy ageing score thereafter. Compared with those with primary education or less, participants with tertiary education had higher baseline scores (adjusted difference in score of 10·54 points, 95% CI 10·31–10·77). The adjusted difference in healthy ageing score between lowest and highest quintiles of wealth was 8·98 points (95% CI 8·74–9·22). Among the eight cohorts, the strongest inequality gradient for both education and wealth was found in the Health Retirement Study from the USA. Interpretation: The apparent difference in baseline healthy ageing scores between those with high versus low education levels and wealth suggests that cumulative disadvantage due to low education and wealth might have largely deteriorated health conditions in early life stages, leading to persistent differences throughout older age, but no further increase in ageing disparity after age 70 years. Future research should adopt a lifecourse approach to investigate mechanisms of health inequalities across education and wealth in different societies. Funding: European Union Horizon 2020 Research and Innovation Programme.The ATHLOS project was funded by the European Union Horizon 2020 Research and Innovation Programme (grant number 635316). This study was supported by the 5-year ATHLOS projec

Repeat-sequence turnover shifts fundamentally in species with large genomes

Given the 2,400-fold range of genome sizes (0.06–148.9 Gbp (gigabase pair)) of seed plants (angiosperms and gymnosperms) with a broadly similar gene content (amounting to approximately 0.03 Gbp), the repeat-sequence content of the genome might be expected to increase with genome size, resulting in the largest genomes consisting almost entirely of repetitive sequences. Here we test this prediction, using the same bioinformatic approach for 101 species to ensure consistency in what constitutes a repeat. We reveal a fundamental change in repeat turnover in genomes above around 10 Gbp, such that species with the largest genomes are only about 55% repetitive. Given that genome size influences many plant traits, habits and life strategies, this fundamental shift in repeat dynamics is likely to affect the evolutionary trajectory of species lineages.We thank Natural Environment Research Council (NE/G020256/1), the Czech Academy of Sciences (RVO:60077344) and Ramón y Cajal Fellowship (RYC-2017-2274) funded by the Ministerio de Ciencia y Tecnología (Gobierno de España) for support. We also thank Natural Environment Research Council for funding a studentship to S.D. and the China Scholarship Council for funding W.W.Abstract Main Methods Data availability Code availability References Acknowledgements Author information Ethics declarations Additional information Extended data Supplementary information Rights and permissions About this article Further readin

The Completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: Measurement of the BAO and growth rate of structure of the luminous red galaxy sample from the anisotropic power spectrum between redshifts 0.6 and 1.0

We analyse the clustering of the Sloan Digital Sky Survey IV extended Baryon Oscillation Spectroscopic Survey Data Release 16 luminous red galaxy sample (DR16 eBOSS LRG) in combination with the high redshift tail of the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey Data Release 12 (DR12 BOSS CMASS).We measure the redshift space distortions (RSD) and also extract the longitudinal and transverse baryonic acoustic oscillation (BAO) scale from the anisotropic power spectrum signal inferred from 377 458 galaxies between redshifts 0.6 and 1.0, with the effective redshift of zeff = 0.698 and effective comoving volume of 2.72 Gpc3. After applying reconstruction, we measure the BAO scale and infer DH(zeff)/rdrag = 19.30 ± 0.56 and DM(zeff)/rdrag = 17.86 ± 0.37. When we perform an RSD analysis on the pre-reconstructed catalogue on the monopole, quadrupole, and hexadecapole we find, DH(zeff)/rdrag = 20.18 ± 0.78, DM(zeff)/rdrag = 17.49 ± 0.52 and fσ8(zeff) = 0.454 ± 0.046. We combine both sets of results along with the measurements in configuration space and report the following consensus values: DH(zeff)/rdrag = 19.77 ± 0.47, DM(zeff)/rdrag = 17.65 ± 0.30 and fσ8(zeff) = 0.473 ± 0.044, which are in full agreement with the standard CDM and GR predictions. These results represent the most precise measurements within the redshift range 0.6 ≤ z ≤ 1.0 and are the culmination of more than 8 yr of SDSS observations

Does Day Length Affect Winter Bird Distribution? Testing the Role of an Elusive Variable

Differences in day length may act as a critical factor in bird biology by introducing time constraints in energy acquisition during winter. Thus, differences in day length might operate as a main determinant of bird abundance along latitudinal gradients. This work examines the influence of day length on the abundance of wintering crested tits (Lophophanes cristatus) in 26 localities of Spanish juniper (Juniperus thurifera) dwarf woodlands (average height of 5 m) located along a latitudinal gradient in the Spanish highlands, while controlling for the influence of food availability, minimum night temperature, habitat structure and landscape characteristics. Top regression models in the AIC framework explained 56% of variance in bird numbers. All models incorporated day length as the variable with the highest magnitude effect. Food availability also played an important role, although only the crop of ripe juniper fruits, but not arthropods, positively affected crested tit abundance. Differences in vegetation structure across localities had also a strong positive effect (average tree height and juniper tree density). Geographical variation in night temperature had no influence on crested tit distribution, despite the low winter temperatures reached in these dwarf forests. This paper demonstrates for the first time that winter bird abundance increases with day length after controlling for the effect of other environmental variables. Winter average difference in day length was only 10.5 minutes per day along the 1°47′ latitudinal interval (190 km) included in this study. This amount of time, which reaches 13.5 h accumulated throughout the winter season, appears to be large enough to affect the long-term energy budget of small passerines during winter and to shape the distribution of winter bird abundance under restrictive environmental conditions