ACAP-A/B Are ArfGAP Homologs in Dictyostelium Involved in Sporulation but Not in Chemotaxis

Arfs and Arf GTPase-activating proteins (ArfGAPs) are regulators of membrane trafficking and actin dynamics in mammalian cells. In this study, we identified a primordial Arf, ArfA, and two ArfGAPs (ACAP-A/B) containing BAR, PH, ArfGAP and Ankyrin repeat domains in the eukaryote Dictyostelium discoideum. In vitro, ArfA has similar nucleotide binding properties as mammalian Arfs and, with GTP bound, is a substrate for ACAP-A and B. We also investigated the physiological functions of ACAP-A/B by characterizing cells lacking both ACAP-A and B. Although ACAP-A/B knockout cells showed no defects in cell growth, migration or chemotaxis, they exhibited abnormal actin protrusions and ∼50% reduction in spore yield. We conclude that while ACAP-A/B have a conserved biochemical mechanism and effect on actin organization, their role in migration is not conserved. The absence of an effect on Dictyostelium migration may be due to a specific requirement for ACAPs in mesenchymal migration, which is observed in epithelial cancer cells where most studies of mammalian ArfGAPs were performed

First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ

Functional analysis of multiple genomic signatures demonstrates that classification algorithms choose phenotype-related genes

Gene expression signatures of toxicity and clinical response benefit both safety assessment and clinical practice; however, difficulties in connecting signature genes with the predicted end points have limited their application. The Microarray Quality Control Consortium II (MAQCII) project generated 262 signatures for ten clinical and three toxicological end points from six gene expression data sets, an unprecedented collection of diverse signatures that has permitted a wide-ranging analysis on the nature of such predictive models. A comprehensive analysis of the genes of these signatures and their nonredundant unions using ontology enrichment, biological network building and interactome connectivity analyses demonstrated the link between gene signatures and the biological basis of their predictive power. Different signatures for a given end point were more similar at the level of biological properties and transcriptional control than at the gene level. Signatures tended to be enriched in function and pathway in an end point and model-specific manner, and showed a topological bias for incoming interactions. Importantly, the level of biological similarity between different signatures for a given end point correlated positively with the accuracy of the signature predictions. These findings will aid the understanding, and application of predictive genomic signatures, and support their broader application in predictive medicine

Universal Artifacts Affect the Branching of Phylogenetic Trees, Not Universal Scaling Laws

The superficial resemblance of phylogenetic trees to other branching structures allows searching for macroevolutionary patterns. However, such trees are just statistical inferences of particular historical events. Recent meta-analyses report finding regularities in the branching pattern of phylogenetic trees. But is this supported by evidence, or are such regularities just methodological artifacts? If so, is there any signal in a phylogeny?In order to evaluate the impact of polytomies and imbalance on tree shape, the distribution of all binary and polytomic trees of up to 7 taxa was assessed in tree-shape space. The relationship between the proportion of outgroups and the amount of imbalance introduced with them was assessed applying four different tree-building methods to 100 combinations from a set of 10 ingroup and 9 outgroup species, and performing covariance analyses. The relevance of this analysis was explored taking 61 published phylogenies, based on nucleic acid sequences and involving various taxa, taxonomic levels, and tree-building methods.All methods of phylogenetic inference are quite sensitive to the artifacts introduced by outgroups. However, published phylogenies appear to be subject to a rather effective, albeit rather intuitive control against such artifacts. The data and methods used to build phylogenetic trees are varied, so any meta-analysis is subject to pitfalls due to their uneven intrinsic merits, which translate into artifacts in tree shape. The binary branching pattern is an imposition of methods, and seldom reflects true relationships in intraspecific analyses, yielding artifactual polytomies in short trees. Above the species level, the departure of real trees from simplistic random models is caused at least by two natural factors--uneven speciation and extinction rates; and artifacts such as choice of taxa included in the analysis, and imbalance introduced by outgroups and basal paraphyletic taxa. This artifactual imbalance accounts for tree shape convergence of large trees.There is no evidence for any universal scaling in the tree of life. Instead, there is a need for improved methods of tree analysis that can be used to discriminate the noise due to outgroups from the phylogenetic signal within the taxon of interest, and to evaluate realistic models of evolution, correcting the retrospective perspective and explicitly recognizing extinction as a driving force. Artifacts are pervasive, and can only be overcome through understanding the structure and biological meaning of phylogenetic trees. Catalan Abstract in Translation S1

Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults.

BACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults. METHODS: We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5-19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity). FINDINGS: Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (-0·01 kg/m2 per decade; 95% credible interval -0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade (0·69-1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per decade (0·64-1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m2 per decade (-0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50-1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4-1·2) in 1975 to 5·6% (4·8-6·5) in 2016 in girls, and from 0·9% (0·5-1·3) in 1975 to 7·8% (6·7-9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0-12·9) in 1975 to 8·4% (6·8-10·1) in 2016 in girls and from 14·8% (10·4-19·5) in 1975 to 12·4% (10·3-14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7-29·6) among girls and 30·7% (23·5-38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide were obese. INTERPRETATION: The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults. FUNDING: Wellcome Trust, AstraZeneca Young Health Programme

Observation of Muon Neutrino Disappearance with the MINOS Detectors in the NuMI Neutrino Beam

This Letter reports results from the MINOS experiment based on its initial exposure to neutrinos from the Fermilab NuMI beam. The rates and energy spectra of charged current νμ interactions are compared in two detectors located along the beam axis at distances of 1 and 735 km. With 1.27×1020 120 GeV protons incident on the NuMI target, 215 events with energies below 30 GeV are observed at the Far Detector, compared to an expectation of 336±14 events. The data are consistent with νμ disappearance via oscillations with |Δm322|=2.74-0.26+0.44×10-3  eV2 and sin⁡2(2θ23)>0.87 (68% C.L.)

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories

Diminishing benefits of urban living for children and adolescents’ growth and development

AbstractOptimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.</jats:p

Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants

Background Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries. Methods We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18·5 kg/m2 [underweight], 18·5 kg/m2 to <20 kg/m2, 20 kg/m2 to <25 kg/m2, 25 kg/m2 to <30 kg/m2, 30 kg/m2 to <35 kg/m2, 35 kg/m2 to <40 kg/m2, ≥40 kg/m2 [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue. Findings We used 1698 population-based data sources, with more than 19·2 million adult participants (9·9 million men and 9·3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21·7 kg/m2 (95% credible interval 21·3–22·1) in 1975 to 24·2 kg/m2 (24·0–24·4) in 2014 in men, and from 22·1 kg/m2 (21·7–22·5) in 1975 to 24·4 kg/m2 (24·2–24·6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21·4 kg/m2 in central Africa and south Asia to 29·2 kg/m2 (28·6–29·8) in Polynesia and Micronesia; for women the range was from 21·8 kg/m2 (21·4–22·3) in south Asia to 32·2 kg/m2 (31·5–32·8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13·8% (10·5–17·4) to 8·8% (7·4–10·3) in men and from 14·6% (11·6–17·9) to 9·7% (8·3–11·1) in women. South Asia had the highest prevalence of underweight in 2014, 23·4% (17·8–29·2) in men and 24·0% (18·9–29·3) in women. Age-standardised prevalence of obesity increased from 3·2% (2·4–4·1) in 1975 to 10·8% (9·7–12·0) in 2014 in men, and from 6·4% (5·1–7·8) to 14·9% (13·6–16·1) in women. 2·3% (2·0–2·7) of the world's men and 5·0% (4·4–5·6) of women were severely obese (ie, have BMI ≥35 kg/m2). Globally, prevalence of morbid obesity was 0·64% (0·46–0·86) in men and 1·6% (1·3–1·9) in women. Interpretation If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world's poorest regions, especially in south Asia