Medical journals and Wikipedia: a global health matter

Approximately 7000 stillbirths occur daily worldwide, and the vast majority of them (98%) Approximately 7000 stillbirths occur daily worldwide, and the vast majority of them (98%) take place in low-income and middle-income countries (LMICs). Despite this enormous burden, progress to reduce the death toll is slow and insufficient. WHO released its Making every baby count guide in 2016, which includes strategies aimed at addressing the challenge of stillbirths. Given the flurry of activity and attention on stillbirths from the Lancet Stillbirth Epidemiology investigator group and WHO, we expect that the wealth of information about stillbirths that is generated will filter down in a timely manner to where it is needed most: the general public

Sex hormone-binding globulin regulation of androgen bioactivity in vivo : validation of the free hormone hypothesis

Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a liganddependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology

Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study

Objective: Long-term androgen deprivation therapy (ADT) negatively influences bone. The short term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Design: Prospective cohort study Methods: Eugonadal adult male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. Results: Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P<0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P<0.0001). Median total estradiol decreased 71% (to 17.6 pmol/L (4.7-35.6); P<0.0001). Increased serum calcium (P<0.0001) and phosphate (P=0.0016) was observed, paralleled by decreased PTH (P=0.0156) and 1,25 dihydroxyvitamin D3 (P=0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P=0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P<0.0001 and P=0.0056, respectively), periostin tended to decrease (P=0.0500) whereas sclerostin increased (P<0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAcP5b, CTX) were unaltered. Conclusions: In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase

Seismic constraints on rotation of Sun-like star and mass of exoplanet

Rotation is thought to drive cyclic magnetic activity in the Sun and Sun-like stars. Stellar dynamos, however, are poorly understood owing to the scarcity of observations of rotation and magnetic fields in stars. Here, inferences are drawn on the internal rotation of a distant Sun-like star by studying its global modes of oscillation. We report asteroseismic constraints imposed on the rotation rate and the inclination of the spin axis of the Sun-like star HD 52265, a principal target observed by the CoRoT satellite that is known to host a planetary companion. These seismic inferences are remarkably consistent with an independent spectroscopic observation (rotational line broadening) and with the observed rotation period of star spots. Furthermore, asteroseismology constrains the mass of exoplanet HD 52265b. Under the standard assumption that the stellar spin axis and the axis of the planetary orbit coincide, the minimum spectroscopic mass of the planet can be converted into a true mass of 1.85 (+0.52,-0.42) M_Jupiter, which implies that it is a planet, not a brown dwarf.Comment: Published in Proceedings of the National Academy of Sciences (5 pages, 5 figures, 3 tables). Available at http://www.pnas.org/cgi/doi/10.1073/pnas.130329111

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

&lt;p&gt;Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.&lt;/p&gt; &lt;p&gt;Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.&lt;/p&gt; &lt;p&gt;Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.&lt;/p&gt; &lt;p&gt;Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.&lt;/p&gt; &lt;p&gt;Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.&lt;/p&gt; &lt;p&gt;Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.&lt;/p&gt

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

&lt;p&gt;Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.&lt;/p&gt; &lt;p&gt;Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.&lt;/p&gt; &lt;p&gt;Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.&lt;/p&gt; &lt;p&gt;Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.&lt;/p&gt; &lt;p&gt;Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.&lt;/p&gt; &lt;p&gt;Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.&lt;/p&gt

A basin-free spherical shape as an outcome of a giant impact on asteroid Hygiea

(10) Hygiea is the fourth largest main belt asteroid and the only known asteroid whose surface composition appears similar to that of the dwarf planet (1) Ceres1,2, suggesting a similar origin for these two objects. Hygiea suffered a giant impact more than 2 Gyr ago3 that is at the origin of one of the largest asteroid families. However, Hygeia has never been observed with sufficiently high resolution to resolve the details of its surface or to constrain its size and shape. Here, we report high-angular-resolution imaging observations of Hygiea with the VLT/SPHERE instrument (~20 mas at 600 nm) that reveal a basin-free nearly spherical shape with a volume-equivalent radius of 217 ± 7 km, implying a density of 1,944 ± 250 kg m−3 to 1σ. In addition, we have determined a new rotation period for Hygiea of ~13.8 h, which is half the currently accepted value. Numerical simulations of the family-forming event show that Hygiea’s spherical shape and family can be explained by a collision with a large projectile (diameter ~75–150 km). By comparing Hygiea’s sphericity with that of other Solar System objects, it appears that Hygiea is nearly as spherical as Ceres, opening up the possibility for this object to be reclassified as a dwarf planet.P.V., A.D. and B.C. were supported by CNRS/INSU/PNP. M.Brož was supported by grant 18-04514J of the Czech Science Foundation. J.H. and J.D. were supported by grant 18-09470S of the Czech Science Foundation and by the Charles University Research Programme no. UNCE/SCI/023. This project has received funding from the European Union’s Horizon 2020 research and innovation programmes under grant agreement nos 730890 and 687378. This material reflects only the authors’ views, and the European Commission is not liable for any use that may be made of the information contained herein. TRAPPIST-North is a project funded by the University of Liège, in collaboration with Cadi Ayyad University of Marrakech (Morocco). TRAPPIST-South is a project funded by the Belgian Fonds (National) de la Recherche Scientifique (F.R.S.-FNRS) under grant FRFC 2.5.594.09.F. E.J. and M.G. are F.R.S.-FNRS Senior Research Associates

Spindle Assembly Checkpoint Protein Dynamics Reveal Conserved and Unsuspected Roles in Plant Cell Division

Background: In eukaryotes, the spindle assembly checkpoint (SAC) ensures that chromosomes undergoing mitosis do not segregate until they are properly attached to the microtubules of the spindle. Methodology/Principal Findings: We investigated the mechanism underlying this surveillance mechanism in plants, by characterising the orthogolous SAC proteins BUBR1, BUB3 and MAD2 from Arabidopsis. We showed that the cell cycle-regulated BUBR1, BUB3.1 and MAD2 proteins interacted physically with each other. Furthermore, BUBR1 and MAD2 interacted specifically at chromocenters. Following SAC activation by global defects in spindle assembly, these three interacting partners localised to unattached kinetochores. In addition, in cases of 'wait anaphase', plant SAC proteins were associated with both kinetochores and kinetochore microtubules. Unexpectedly, BUB3.1 was also found in the phragmoplast midline during the final step of cell division in plants. Conclusions/Significance: We conclude that plant BUBR1, BUB3.1 and MAD2 proteins may have the SAC protein functions conserved from yeast to humans. The association of BUB3.1 with both unattached kinetochore and phragmoplast suggests that in plant, BUB3.1 may have other roles beyond the spindle assembly checkpoint itself. Finally, this study of the SAC dynamics pinpoints uncharacterised roles of this surveillance mechanism in plant cell division

Towards comprehensive observing and modeling systems for monitoring and predicting regional to coastal sea level

A major challenge for managing impacts and implementing effective mitigation measures and adaptation strategies for coastal zones affected by future sea level (SL) rise is our limited capacity to predict SL change at the coast on relevant spatial and temporal scales. Predicting coastal SL requires the ability to monitor and simulate a multitude of physical processes affecting SL, from local effects of wind waves and river runoff to remote influences of the large-scale ocean circulation on the coast. Here we assess our current understanding of the causes of coastal SL variability on monthly to multi-decadal timescales, including geodetic, oceanographic and atmospheric aspects of the problem, and review available observing systems informing on coastal SL. We also review the ability of existing models and data assimilation systems to estimate coastal SL variations and of atmosphere-ocean global coupled models and related regional downscaling efforts to project future SL changes. We discuss (1) observational gaps and uncertainties, and priorities for the development of an optimal and integrated coastal SL observing system, (2) strategies for advancing model capabilities in forecasting short-term processes and projecting long-term changes affecting coastal SL, and (3) possible future developments of sea level services enabling better connection of scientists and user communities and facilitating assessment and decision making for adaptation to future coastal SL change.RP was funded by NASA grant NNH16CT00C. CD was supported by the Australian Research Council (FT130101532 and DP 160103130), the Scientific Committee on Oceanic Research (SCOR) Working Group 148, funded by national SCOR committees and a grant to SCOR from the U.S. National Science Foundation (Grant OCE-1546580), and the Intergovernmental Oceanographic Commission of UNESCO/International Oceanographic Data and Information Exchange (IOC/IODE) IQuOD Steering Group. SJ was supported by the Natural Environmental Research Council under Grant Agreement No. NE/P01517/1 and by the EPSRC NEWTON Fund Sustainable Deltas Programme, Grant Number EP/R024537/1. RvdW received funding from NWO, Grant 866.13.001. WH was supported by NASA (NNX17AI63G and NNX17AH25G). CL was supported by NASA Grant NNH16CT01C. This work is a contribution to the PIRATE project funded by CNES (to TP). PT was supported by the NOAA Research Global Ocean Monitoring and Observing Program through its sponsorship of UHSLC (NA16NMF4320058). JS was supported by EU contract 730030 (call H2020-EO-2016, “CEASELESS”). JW was supported by EU Horizon 2020 Grant 633211, Atlantos

A multi-scale analysis of bull sperm methylome revealed both species peculiarities and conserved tissue-specific

peer-reviewedBackground: Spermatozoa have a remarkable epigenome in line with their degree of specialization, their unique nature and different requirements for successful fertilization. Accordingly, perturbations in the establishment of DNA methylation patterns during male germ cell differentiation have been associated with infertility in several species.Background: Spermatozoa have a remarkable epigenResults: The quantification of DNA methylation at CCGG sites using luminometric methylation assay (LUMA) highlighted the undermethylation of bull sperm compared to the sperm of rams, stallions, mice, goats and men. Total blood cells displayed a similarly high level of methylation in bulls and rams, suggesting that undermethylation of the bovine genome was specific to sperm. Annotation of CCGG sites in different species revealed no striking bias in the distribution of genome features targeted by LUMA that could explain undermethylation of bull sperm. To map DNA methylation at a genome-wide scale, bull sperm was compared with bovine liver, fibroblasts and monocytes using reduced representation bisulfite sequencing (RRBS) and immunoprecipitation of methylated DNA followed by microarray hybridization (MeDIP-chip). These two methods exhibited differences in terms of genome coverage, and consistently, two independent sets of sequences differentially methylated in sperm and somatic cells were identified for RRBS and MeDIP-chip. Remarkably, in the two sets most of the differentially methylated sequences were hypomethylated in sperm. In agreement with previous studies in other species, the sequences that were specifically hypomethylated in bull sperm targeted processes relevant to the germline differentiation program (piRNA metabolism, meiosis, spermatogenesis) and sperm functions (cell adhesion, fertilization), as well as satellites and rDNA repeats. Conclusions: These results highlight the undermethylation of bull spermatozoa when compared with both bovine somatic cells and the sperm of other mammals, and raise questions regarding the dynamics of DNA methylation in bovine male germline. Whether sperm undermethylation has potential interactions with structural variation in the cattle genome may deserve further attention. While bull semen is widely used in artificial insemination, the literature describing DNA methylation in bull spermatozoa is still scarce. The purpose of this study was therefore to characterize the bull sperm methylome relative to both bovine somatic cells and the sperm of other mammals through a multiscale analysis