The Role of Extramembranous Cytoplasmic Termini in Assembly and Stability of the Tetrameric K+-Channel KcsA

Membrane-active alcohol 2,2,2-trifluoroethanol has been proven to be an attractive tool in the investigation of the intrinsic stability of integral membrane protein complexes by taking K+-channel KcsA as a suitable and representative ion channel. In the present study, the roles of both cytoplasmic N and C termini in channel assembly and stability of KcsA were determined. The N terminus (1–18 residues) slightly increased tetramer stability via electrostatic interactions in the presence of 30 mol.% acidic phosphatidylglycerol (PG) in phosphatidylcholine lipid bilayer. Furthermore, the N terminus was found to be potentially required for efficient channel (re)assembly. In contrast, truncation of the C terminus (125–160 residues) greatly facilitated channel reversibility from either a partially or a completely unfolded state, and this domain was substantially involved in stabilizing the tetramer in either the presence or absence of PG in lipid bilayer. These studies provide new insights into how extramembranous parts play their crucial roles in the assembly and stability of integral membrane protein complexes

Retroviral matrix and lipids, the intimate interaction

Retroviruses are enveloped viruses that assemble on the inner leaflet of cellular membranes. Improving biophysical techniques has recently unveiled many molecular aspects of the interaction between the retroviral structural protein Gag and the cellular membrane lipids. This interaction is driven by the N-terminal matrix domain of the protein, which probably undergoes important structural modifications during this process, and could induce membrane lipid distribution changes as well. This review aims at describing the molecular events occurring during MA-membrane interaction, and pointing out their consequences in terms of viral assembly. The striking conservation of the matrix membrane binding mode among retroviruses indicates that this particular step is most probably a relevant target for antiviral research

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

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

Growth and length-weight relationship of the striped marlin, Tetrapturus audax (Pisces: Istiophoridae), in Cabo San Lucas, Baja California Sur, Mexico

 To determine the age, backcalculate the length, and describe the individual growth and length-weight relationship of the striped marlin Tetrapturus audax, the catch of the sport-fishing fleet from Cabo San Lucas, Mexico, was sampled from 1988 to 1993. The length and weight of 1044 fishes were measured, and the fourth spine of the dorsal fin was collected from 399 of them. The mandibular length (ML) ranged from 156 to 263 cm, and the total weight (TW) ranged from 26 to 100 kg. No significant differences were detected (P > 0.05) in the ML-TW relationship either between sexes or between years. The general relationship was TW = 0.00008*ML(2.523), showing a negative allometric growth (b < 3, P < 0.05). Ten age groups were determined (2 to 11). The relationship between ML and the dorsal fin radius was highly significant (P < 0.001), justifying the use of the dorsal fin for the age determination and to describe the growth of the striped marlin. The von Bertalanffy growth model was fitted appropriately to backcalculated ML-age data (r2 = 0.99) and the values of the parameters were: L∞ = 221 cm, K = 0.23 per year, and t0 = –1.6. The striped marlin reaches 45% of the asymptotic length in its first year of life; in the second year the growth rate decreases to 10%, and during the next eight years the growth rate is 4% on average. The present study is the first to report on the individual growth of the striped marlin based on age determination in hard structures

Age and growth of Pacific golden-eye tilefish (Caulolatilus affinis) in the central region of the Gulf of California

Age, growth, and the length-weight relationship were estimated for the Pacific golden-eye tilefish Caulolatilus affinis captured by the artisanal fishery in the central region of the Gulf of California. The size and weight structure differed between sexes, males being larger and heavier than females; however, differences in the length-weight relationship were not detected and the slope value (b = 2.66) showed that it was a negative allometric relationship. The youngest and oldest organisms were 3 and 21 years old, respectively. The age structure showed differences between sexes, males being more abundant at older ages and females at younger ones. The dominant age group for females was 11 years old and for males, 16 years old. The von Bertalanffy growth model fitted adequately the mean size and age data; the model parameters were L∞ = 432.32 mm total length, k = 0.232 mm yr–1, and t0 = 0.164 yr for males, and L∞ = 422.99 mm total length, k = 0.245 mm yr–1, and t0 = –0.095 yr for females. Differences in individual growth and growth rate between males and females were not detected. According to the age structure and growth pattern, C. affinis is a slow-growing, medium-lived species. Our results suggest that C. affinis is underexploited in the central Gulf of California because it is a non-target species.

Differences in the length-age relationship of the snail Astraea undosa (Wood, 1828) between two localities of Tortugas Bay, Baja California Sur, Mexico

The differences in basal diameter (DB), age and DB-age of the snail Astraea undosa in two zones of Tortugas Bay (Mexico) were studied from November 1996 to November 1997. Age was determined by counting the opercular growth marks. The age groups were annual. The interval size was of 49 to 118 mm DB in snails of 2 to 12 years of age. Monthly frequency distributions of the DB and of age between zones were significantly different, except for the age distributions of November 1996, and June and November 1997. The legal minimum catch size (90 mm DB) is reached in one zone at 5 years and in the other at 9 years, on average, indicating a different growth pattern between zones. The differences in DB-age between zones were significant at 4 years of age. To promote a rapid growth of the snails from the slowgrowth zone, we suggest moving individuals of ≥63 mm DB to better growth zones

Iodine and Iron deficiency and Parasites in children of Arandas, Mexico during the nutrition transition

Tordeur Pol. Louis Callebat et Jean Soubiran, Priapées. Texte établi, traduit et commenté par L. C. Étude métrique par J. S. Paris, Les Belles Lettres, 2012 (Collection des Universités de France). In: L'antiquité classique, Tome 83, 2014. p. 295