γ-Glutamyltransferase, but not markers of hepatic fibrosis, is associated with cardiovascular disease in older people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study

AIMS/HYPOTHESIS: We examined the association of prevalent and incident cardiovascular disease (CVD) with chronic liver disease in a cohort of community-based people with type 2 diabetes, in order to clarify the relationship between these two important conditions. METHODS: 1,066 participants with type 2 diabetes aged 60–75 years underwent assessment of a range of liver injury markers (non-specific injury, steatosis, steatohepatitis, fibrosis, portal hypertension). Individuals were followed up for incident cardiovascular events. RESULTS: At baseline there were 370/1,033 patients with prevalent CVD, including 317/1,033 with coronary artery disease (CAD). After a mean follow-up of 4.4 years there were 44/663 incident CVD events, including 27/663 CAD events. There were 30/82 CVD-related deaths. Risk of dying from or developing CVD was no higher in participants with steatosis than in those without (HR 0.90; 95% CI 0.40, 2.00; p > 0.05). The only notable relationship was with γ-glutamyltransferase (GGT) (incident CVD: adjusted HR for doubling GGT 1.24 [95% CI 0.97, 1.59] p = 0.086; incident CAD: adjusted HR 1.33 [95% CI 1.00, 1.78] p = 0.053), suggesting that in our study population, chronic liver disease may have little effect on the development of, or mortality from, CVD. CONCLUSIONS/INTERPRETATION: An independent association between GGT and CVD warrants further exploration as a potentially useful addition to current cardiovascular risk prediction models in diabetes. However, overall findings failed to suggest that there is a clinical or pathophysiological association between chronic liver disease and CVD in elderly people with type 2 diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3575-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users

A genetically anchored physical framework for Theobroma cacao cv. Matina 1-6

<p>Abstract</p> <p>Background</p> <p>The fermented dried seeds of <it>Theobroma cacao </it>(cacao tree) are the main ingredient in chocolate. World cocoa production was estimated to be 3 million tons in 2010 with an annual estimated average growth rate of 2.2%. The cacao bean production industry is currently under threat from a rise in fungal diseases including black pod, frosty pod, and witches' broom. In order to address these issues, genome-sequencing efforts have been initiated recently to facilitate identification of genetic markers and genes that could be utilized to accelerate the release of robust <it>T. cacao </it>cultivars. However, problems inherent with assembly and resolution of distal regions of complex eukaryotic genomes, such as gaps, chimeric joins, and unresolvable repeat-induced compressions, have been unavoidably encountered with the sequencing strategies selected.</p> <p>Results</p> <p>Here, we describe the construction of a BAC-based integrated genetic-physical map of the <it>T. cacao </it>cultivar Matina 1-6 which is designed to augment and enhance these sequencing efforts. Three BAC libraries, each comprised of 10× coverage, were constructed and fingerprinted. 230 genetic markers from a high-resolution genetic recombination map and 96 Arabidopsis-derived conserved ortholog set (COS) II markers were anchored using pooled overgo hybridization. A dense tile path consisting of 29,383 BACs was selected and end-sequenced. The physical map consists of 154 contigs and 4,268 singletons. Forty-nine contigs are genetically anchored and ordered to chromosomes for a total span of 307.2 Mbp. The unanchored contigs (105) span 67.4 Mbp and therefore the estimated genome size of <it>T. cacao </it>is 374.6 Mbp. A comparative analysis with <it>A. thaliana, V. vinifera</it>, and <it>P. trichocarpa </it>suggests that comparisons of the genome assemblies of these distantly related species could provide insights into genome structure, evolutionary history, conservation of functional sites, and improvements in physical map assembly. A comparison between the two <it>T. cacao </it>cultivars Matina 1-6 and Criollo indicates a high degree of collinearity in their genomes, yet rearrangements were also observed.</p> <p>Conclusions</p> <p>The results presented in this study are a stand-alone resource for functional exploitation and enhancement of <it>Theobroma cacao </it>but are also expected to complement and augment ongoing genome-sequencing efforts. This resource will serve as a template for refinement of the <it>T. cacao </it>genome through gap-filling, targeted re-sequencing, and resolution of repetitive DNA arrays.</p

Dimer Formation Enhances Structural Differences between Amyloid β-Protein (1–40) and (1–42): An Explicit-Solvent Molecular Dynamics Study

Amyloid -protein (A) is central to the pathology of Alzheimer's disease. A 5% difference in the primary structure of the two predominant alloforms, A and A, results in distinct assembly pathways and toxicity properties. Discrete molecular dynamics (DMD) studies of A and A assembly resulted in alloform-specific oligomer size distributions consistent with experimental findings. Here, a large ensemble of DMD–derived A and A monomers and dimers was subjected to fully atomistic molecular dynamics (MD) simulations using the OPLS-AA force field combined with two water models, SPCE and TIP3P. The resulting all-atom conformations were slightly larger, less compact, had similar turn and lower -strand propensities than those predicted by DMD. Fully atomistic A and A monomers populated qualitatively similar free energy landscapes. In contrast, the free energy landscape of A dimers indicated a larger conformational variability in comparison to that of A dimers. A dimers were characterized by an increased flexibility in the N-terminal region D1-R5 and a larger solvent exposure of charged amino acids relative to A dimers. Of the three positively charged amino acids, R5 was the most and K16 the least involved in salt bridge formation. This result was independent of the water model, alloform, and assembly state. Overall, salt bridge propensities increased upon dimer formation. An exception was the salt bridge propensity of K28, which decreased upon formation of A dimers and was significantly lower than in A dimers. The potential relevance of the three positively charged amino acids in mediating the A oligomer toxicity is discussed in the light of available experimental data

Measurement of the top-quark mass in tt¯ events with dilepton final states in pp collisions at √s = 7 TeV

Open Access: This article is distributed under the terms of the Creative Commons Attribution License.-- Chatrchyan, S. et al.The top-quark mass is measured in proton-proton collisions at s√=7 TeV using a data sample corresponding to an integrated luminosity of 5.0 fb−1 collected by the CMS experiment at the LHC. The measurement is performed in the dilepton decay channel tt¯→(ℓ+νℓb)(ℓ−ν¯¯ℓb¯), where ℓ=e,μ. Candidate top-quark decays are selected by requiring two leptons, at least two jets, and imbalance in transverse momentum. The mass is reconstructed with an analytical matrix weighting technique using distributions derived from simulated samples. Using a maximum-likelihood fit, the top-quark mass is determined to be 172.5±0.4 (stat.)±1.5 (syst.) GeV.Acknowledge support from BMWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); MoER, SF0690030s09 and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France);BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); MSI (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MON, RosAtom, RAS and RFBR (Russia); MSTD (Serbia); SEIDI and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); ThEP, IPST and NECTEC (Thailand); TUBITAK and TAEK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie program and the European Research Council (European Union); the Leventis Foundation; the A. P. Sloan Foundation; the Alexander von Humboldt Foundation; the Austrian Science Fund (FWF); the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWTBelgium); the Ministry of Education, Youth and Sports (MEYS) of Czech Republic; the Council of Science and Industrial Research, India; the Compagnia di San Paolo (Torino); and the HOMING PLUS program of Foundation for Polish Science, cofinanced from European Union, Regional Development Fund.Peer Reviewe

Copper Induced Lysosomal Membrane Destabilisation in Haemolymph Cells of Mediterranean Green Crab (Carcinus aestuarii, Nardo, 1847) from the Narta Lagoon (Albania)

ABSTRACTDestabilisation of blood cell lysosomes in Mediterranean green crabCarcinus aestuarii was investigated using Neutral Red Retention Assay (NRRA). Crabs collected in Narta Lagoon, Vlora (Albania) during May 2014 were exposed in the laboratory to sub-lethal, environmentally realistic concentrations of copper. Neutral Red Retention Time (NRRT) and glucose concentration in haemolymph of animals were measured. The mean NRRT showed a significant reduction for the animals of the treatment group compared to the control one (from 118.6 ± 28.4 to 36.4 ± 10.48 min, p<0.05), indicating damage of lysosomal membrane. Haemolymph glucose concentration was significantly higher in the treatment group (from 37.8 ± 2.7 to 137.8.4 ± 16.2 mg/dL, p<0.05) than in control group, demonstrating the presence of stress on the animals. These results showed thatC. aestuarii could be used as a successful and reliable bioindicator for evaluating the exposure to contaminants in laboratory conditions. NRRA provides a successful tool for rapid assessment of heavy metal pollution effects on marine biota

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity. Funding UK Medical Research Council, UK Research and Innovation (Research England), UK Research and Innovation (Innovate UK), and European Union

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

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity