Primate iPS cells as tools for evolutionary analyses

Induced pluripotent stem cells (iPSCs) are regarded as a central tool to understand human biology in health and disease. Similarly, iPSCs from non-human primates should be a central tool to understand human evolution, in particular for assessing the conservation of regulatory networks in iPSC models. Here, we have generated human, gorilla, bonobo and cynomolgus monkey iPSCs and assess their usefulness in such a framework. We show that these cells are well comparable in their differentiation potential and are generally similar to human, cynomolgus and rhesus monkey embryonic stem cells (ESCs). RNA sequencing reveals that expression differences among clones, individuals and stem cell type are all of very similar magnitude within a species. In contrast, expression differences between closely related primate species are three times larger and most genes show significant expression differences among the analyzed species. However, pseudogenes differ more than twice as much, suggesting that evolution of expression levels in primate stem cells is rapid, but constrained. These patterns in pluripotent stem cells are comparable to those found in other tissues except testis. Hence, primate iPSCs reveal insights into general primate gene expression evolution and should provide a rich source to identify conserved and species-specific gene expression patterns for cellular phenotypes

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A Comprehensive Microarray-Based DNA Methylation Study of 367 Hematological Neoplasms

Background: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings: Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance: We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1 that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs

EarthFinder Probe Mission Concept Study: Characterizing nearby stellar exoplanet systems with Earth-mass analogs for future direct imaging

EarthFinder is a NASA Astrophysics Probe mission concept selected for study as input to the 2020 Astrophysics National Academies Decadal Survey. The EarthFinder concept is based on a dramatic shift in our understanding of how PRV measurements should be made. We propose a new paradigm which brings the high precision, high cadence domain of transit photometry as demonstrated by Kepler and TESS to the challenges of PRV measurements at the cm/s level. This new paradigm takes advantage of: 1) broad wavelength coverage from the UV to NIR which is only possible from space to minimize the effects of stellar activity; 2) extremely compact, highly stable, highly efficient spectrometers (R>150,000) which require the diffraction-limited imaging possible only from space over a broad wavelength range; 3) the revolution in laser-based wavelength standards to ensure cm/s precision over many years; 4) a high cadence observing program which minimizes sampling-induced period aliases; 5) exploiting the absolute flux stability from space for continuum normalization for unprecedented line-by-line analysis not possible from the ground; and 6) focusing on the bright stars which will be the targets of future imaging missions so that EarthFinder can use a ~1.5 m telescope

Methodology and implementation of the WHO European Childhood Obesity Surveillance Initiative (COSI)

Establishment of the WHO European Childhood Obesity Surveillance Initiative (COSI)has resulted in a surveillance system which provides regular, reliable, timely, andaccurate data on children's weight status—through standardized measurement ofbodyweight and height—in the WHO European Region. Additional data on dietaryintake, physical activity, sedentary behavior, family background, and schoolenvironments are collected in several countries. In total, 45 countries in the EuropeanRegion have participated in COSI. The first five data collection rounds, between 2007and 2021, yielded measured anthropometric data on over 1.3 million children. In COSI,data are collected according to a common protocol, using standardized instrumentsand procedures. The systematic collection and analysis of these data enables inter-country comparisons and reveals differences in the prevalence of childhood thinness,overweight, normal weight, and obesity between and within populations. Furthermore,it facilitates investigation of the relationship between overweight, obesity, and poten-tial risk or protective factors and improves the understanding of the development ofoverweight and obesity in European primary-school children in order to supportappropriate and effective policy responses.The authors gratefully acknowledge support through a grant from the Russian Government in the context of the WHO European Office for the Prevention and Control of NCDs. The ministries of health of Austria, Croatia, Greece, Italy, Malta, Norway, and the Russian Federation provided financial support for the meetings at which the protocol, data collection procedures, and analyses were discussed. Data collection in countries was made possible through funding from the following: Albania: WHO through the Joint Programme on Children, Food Security and Nutrition “Reducing Malnutrition in Children,” funded by the Millennium Development Goals Achievement Fund, and the Institute of Public Health. Austria: Federal Ministry of Labor, Social Affairs, Health and Consumer Protection of Austria. Bulgaria: Ministry of Health, National Center of Public Health and Analyses, and WHO Regional Office for Europe. Bosnia and Herzegovina: WHO country office support for training and data management. Croatia: Ministry of Health, Croatian Institute of Public Health, and WHO Regional Office for Europe. Czechia: Ministry of Health of the Czech Republic, grant number 17-31670A and MZCR—RVO EU 00023761. Denmark: Danish Ministry of Health. Estonia: Ministry of Social Affairs, Ministry of Education and Research (IUT 42-2), WHO Country Office, and National Institute for Health Development. Finland: Finnish Institute for Health and Welfare. France: Santé publique France (the French Agency for Public Health). Georgia: WHO. Greece: International Hellenic University and Hellenic Medical Association for Obesity. Hungary: WHO Country Office for Hungary. Ireland: Health Service Executive. Italy: Ministry of Health. Kazakhstan: Ministry of Health of the Republic of Kazakhstan, WHO, and UNICEF. Kyrgyzstan: World Health Organization. Latvia: Ministry of Health and Centre for Disease Prevention and Control. Lithuania: Science Foundation of Lithuanian University of Health Sciences and Lithuanian Science Council and WHO. Malta: Ministry of Health. Montenegro: WHO and Institute of Public Health of Montenegro. North Macedonia: Government of North Macedonia through National Annual Program of Public Health and implemented by the Institute of Public Health and Centers of Public Health; WHO country office provides support for training and data management. Norway: the Norwegian Ministry of Health and Care Services, the Norwegian Directorate of Health, and the Norwegian Institute of Public Health. Poland: National Health Programme, Ministry of Health. Portugal: Ministry of Health Institutions, the National Institute of Health, Directorate General of Health, Regional Health Directorates, and the kind technical support from the Center for Studies and Research on Social Dynamics and Health (CEIDSS). Romania: Ministry of Health. Russian Federation: WHO. San Marino: Health Ministry, Educational Ministry, and Social Security Institute and Health Authority. Serbia: WHO and the WHO Country Office (2015-540940 and 2018/873491-0). Slovakia: Biennial Collaborative Agreement between WHO Regional Office for Europe and Ministry of Health SR. Slovenia: Ministry of Education, Science and Sport of the Republic of Slovenia within the SLOfit surveillance system. Spain: Spanish Agency for Food Safety and Nutrition. Sweden: Public Health Agency of Sweden. Tajikistan: WHO Country Office in Tajikistan and Ministry of Health and Social Protection. Turkmenistan: WHO Country Office in Turkmenistan and Ministry of Health. Turkey: Turkish Ministry of Health and World Bank.info:eu-repo/semantics/publishedVersio

The pipeline project:Pre-publication independent replications of a single laboratory's research pipeline

This crowdsourced project introduces a collaborative approach to improving the reproducibility of scientific research, in which findings are replicated in qualified independent laboratories before (rather than after) they are published. Our goal is to establish a non-adversarial replication process with highly informative final results. To illustrate the Pre-Publication Independent Replication (PPIR) approach, 25 research groups conducted replications of all ten moral judgment effects which the last author and his collaborators had "in the pipeline" as of August 2014. Six findings replicated according to all replication criteria, one finding replicated but with a significantly smaller effect size than the original, one finding replicated consistently in the original culture but not outside of it, and two findings failed to find support. In total, 40% of the original findings failed at least one major replication criterion. Potential ways to implement and incentivize pre-publication independent replication on a large scale are discussed. (C) 2015 The Authors. Published by Elsevier Inc.</p

Thinness, overweight, and obesity in 6‐ to 9‐year‐old children from 36 countries: The World Health Organization European Childhood Obesity Surveillance Initiative - COSI 2015-2017

In 2015-2017, the fourth round of the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative (COSI) was conducted in 36 countries. National representative samples of children aged 6–9 (203,323) were measured by trained staff, with similar equipment and using a standardized protocol. This paper assesses the children's body weight status and compares the burden of childhood overweight, obesity, and thinness in Northern, Eastern, and Southern Europe and Central Asia. The results show great geographic variability in height, weight, and body mass index. On average, the children of Northern Europe were the tallest, those of Southern Europe the heaviest, and the children living in Central Asia the lightest and the shortest. Overall, 28.7% of boys and 26.5% of girls were overweight (including obesity) and 2.5% and 1.9%, respectively, were thin according to the WHO definitions. The prevalence of obesity varied from 1.8% of boys and 1.1% of girls in Tajikistan to 21.5% and 19.2%, respectively, in Cyprus, and tended to be higher for boys than for girls. Levels of thinness, stunting, and underweight were relatively low, except in Eastern Europe (for thinness) and in Central Asia. Despite the efforts to halt it, unhealthy weight status is still an important problem in the WHO European Region.The authors gratefully acknowledge support from a grant from the Russian Government in the context of the WHO European Office for the Prevention and Control of NCDs. Data collection in the countries was made possible through funding from the following: Albania: WHO through the Joint Programme on Children, Food Security and Nutrition “Reducing Malnutrition in Children,” funded by the Millennium Development Goals Achievement Fund, and the Institute of Public Health; Austria: Federal Ministry of Social Affairs, Health, Care and Consumer Protection, Republic of Austria; Bulgaria: Ministry of Health, National Center of Public Health and Analyses, WHO Regional Office for Europe; Croatia: Ministry of Health, Croatian Institute of Public Health and WHO Regional Office for Europe; Czechia: Ministry of Health of the Czech Republic, grants AZV MZČR 17-31670 A and MZČR – RVO EÚ 00023761; Cyprus: not available; Denmark: Danish Ministry of Health; Estonia: Ministry of Social Affairs, Ministry of Education and Research (IUT 42-2), WHO Country Office, and National Institute for Health Development; Finland: Finnish Institute for Health and Welfare; France: Santé publique France, the French Agency for Public Health; Georgia: WHO; Greece: International Hellenic University and Hellenic Medical Association for Obesity; Hungary: WHO Country Office for Hungary; Ireland: Health Service Executive; Italy: Ministry of Health and Italian National Institute of Health; Kazakhstan: Ministry of Health of the Republic of Kazakhstan and WHO Country Office; Kyrgyzstan: World Health Organization; Latvia: Ministry of Health, Centre for Disease Prevention and Control; Lithuania: Science Foundation of Lithuanian University of Health Sciences and Lithuanian Science Council and WHO; Malta: Ministry of Health; Montenegro: WHO and Institute of Public Health of Montenegro; North Macedonia: funded by the Government of North Macedonia through National Annual Program of Public Health and implemented by the Institute of Public Health and Centers of Public Health in the country. WHO country office provided support for training and data management; Norway: Ministry of Health and Norwegian Institute of Public Health; Poland: National Health Programme, Ministry of Health; Portugal: Ministry of Health Institutions, the National Institute of Health, Directorate General of Health, Regional Health Directorates and the kind technical support from the Center for Studies and Research on Social Dynamics and Health (CEIDSS); Romania: Ministry of Health; Russian Federation: WHO; San Marino: Health Ministry, Educational Ministry, Social Security Institute and Health Authority; Serbia: World Health Organization (Ref. File 2015-540940); Slovakia: Biennial Collaborative Agreement between WHO Regional Office for Europe and Ministry of Health SR; Slovenia: Ministry of Education, Science and Sport of the Republic of Slovenia within the SLOfit surveillance system; Spain: Spanish Agency for Food Safety and Nutrition (AESAN); Sweden: Public Health Agency of Sweden; Tajikistan: WHO Country Office in Tajikistan and Ministry of Health and Social Protection; Turkmenistan: WHO Country Office in Turkmenistan and Ministry of Health; Turkey: Turkish Ministry of Health and World Bank.info:eu-repo/semantics/publishedVersio

A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants.

Background The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. Trial registration The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011

Data from a pre-publication independent replication initiative examining ten moral judgement effects

We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that researchers can use to better understand reproducibility and irreproducibility in science