Human long intrinsically disordered protein regions are frequent targets of positive selection

Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher-order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here we address this question by investigating the evolutionary pattern of more than 6,600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a-priori knowledge of disordered protein regions and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs 4-fold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts

A Century of Change towards Prevention and Minimal Intervention in Cariology

Publisher Copyright: © International & American Associations for Dental Research 2019. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.Better understanding of dental caries and other oral conditions has guided new strategies to prevent disease and manage its consequences at individual and public health levels. This article discusses advances in prevention and minimal intervention dentistry over the last century by focusing on some milestones within scientific, clinical, and public health arenas, mainly in cariology but also beyond, highlighting current understanding and evidence with future prospects. Dentistry was initially established as a surgical specialty. Dental caries (similar to periodontitis) was considered to be an infectious disease 100 years ago. Its ubiquitous presence and rampant nature—coupled with limited diagnostic tools and therapeutic treatment options—meant that these dental diseases were managed mainly by excising affected tissue. The understanding of the diseases and a change in their prevalence, extent, and severity, with evolutions in operative techniques, technologies, and materials, have enabled a shift from surgical to preventive and minimal intervention dentistry approaches. Future challenges to embrace include continuing the dental profession’s move toward a more patient-centered, evidence-based, less invasive management of these diseases, focused on promoting and maintaining oral health in partnership with patients. In parallel, public health needs to continue to, for example, tackle social inequalities in dental health, develop better preventive and management options for existing disease risk groups (e.g., the growing aging population), and the development of reimbursement and health outcome models that facilitate implementation of these evolving strategies. A century ago, almost every treatment involved injections, a drill or scalpel, or a pair of forceps. Today, dentists have more options than ever before available to them. These are supported by evidence, have a minimal intervention focus, and result in better outcomes for patients. The profession’s greatest challenge is moving this evidence into practice.preprintPeer reviewe

Electronic structure of the muonium center as a shallow donor in ZnO

The electronic structure and the location of muonium centers (Mu) in single-crystalline ZnO were determined for the first time. Two species of Mu centers with extremely small hyperfine parameters have been observed below 40 K. Both Mu centers have an axial-symmetric hyperfine structure along with a [0001] axis, indicating that they are located at the AB_{O,//} and BC_{//} sites. It is inferred from their small ionization energy (~6 meV and 50 meV) and hyperfine parameters (~10^{-4} times the vacuum value) that these centers behave as shallow donors, strongly suggesting that hydrogen is one of the primary origins of n type conductivity in as-grown ZnO.Comment: 4 pages, 4 figures, submitted to PR

Weight-Related Behavior among Adolescents: The Role of Peer Effects

To investigate whether social interactions in friendship networks influence the following weight-related behaviors of adolescents: exercising regularly, playing an active sport, hours of TV/Video viewing, sleeping six or fewer hours, eating breakfast on weekdays, frequency of eating at fast food restaurants, eating five servings of fruits/vegetables daily, and consuming calorie-dense snacks.Data from a nationally representative sample of adolescents are used to examine the association between peer and individual weight-related behaviors. Evidence from multivariate regression analysis controlling for an extensive list of individual- and family-level factors as well as school-level unobserved heterogeneity is obtained.We find a significant positive association between individuals' and friends' behaviors in terms of sports, exercise and fast food consumption. The estimated associations are robust to controls for individual- and family-level factors, unobserved heterogeneity at the school level and our attempts to account for non-random peer selection.The social transmission of weight-related behaviors is a viable explanation for the spread of obesity in friendship networks documented in recent research. Traditional weight reduction interventions may be fruitfully complemented with strategies that focus on harnessing peer support to modify behaviors

Fertility Ideals of Women and Men Across the Life Course

This paper explores the stability of women’s and men’s fertility preferences across the life course. The data come from the first six waves of the German Family Panel (pairfam), which span the period from 2008/2009 until 2013/2014. In our analysis, fertility preferences are measured using the following question: “Under ideal circumstances, how many children would you like to have?” The average number cited by both women and men is 2.2. With rising age, this number declines modestly. Relying on fixed-effects modelling, we find that neither partnership status nor economic circumstances have any causal effect on fertility preferences. However, as the number of children a respondent has increases, his or her ideal number of children is also likely to grow. Thus, fertility ideals appear to undergo changes over time, and are adjusted in line with the size of the respondent’s own family

Welcome to the family: Identification of the nad+ transporter of animal mitochondria as member of the solute carrier family slc25

Subcellular compartmentation is a fundamental property of eukaryotic cells. Communication and metabolic and regulatory interconnectivity between organelles require that solutes can be transported across their surrounding membranes. Indeed, in mammals, there are hundreds of genes encoding solute carriers (SLCs) which mediate the selective transport of molecules such as nucleotides, amino acids, and sugars across biological membranes. Research over many years has identified the localization and preferred substrates of a large variety of SLCs. Of particular interest has been the SLC25 family, which includes carriers embedded in the inner membrane of mitochondria to secure the supply of these organelles with major metabolic intermediates and coen-zymes. The substrate specificity of many of these carriers has been established in the past. However, the route by which animal mitochondria are supplied with NAD+ had long remained obscure. Only just recently, the existence of a human mitochondrial NAD+ carrier was firmly established. With the realization that SLC25A51 (or MCART1) represents the major mitochondrial NAD+ carrier in mammals, a long-standing mystery in NAD+ biology has been resolved. Here, we summarize the functional importance and structural features of this carrier as well as the key observations leading to its discovery

Family-Friendly Management, Organizational Performance and Social Legitimacy

Research on family-friendly practices has concentrated on the predictors of their use, particularly from the perspective of either institutional theory or the high involvement or commitment management vogue. This paper first shows how such perspectives can be used to generate hypotheses about the link between family-friendly management and organizational performance. Second, the paper reports research designed to test these, using data from a national representative sample of workplaces across the British economy, the Workplace Employment Relations Survey of 2004 (WERS2004). The results support the high commitment thesis that family-friendly management will strengthen the relationship between commitment and key economic outcomes, as the relationships between workforce commitment and productivity or quality are stronger in organizations when friendly management is high, which is consistent with social exchange theory. Family-friendly management is not, however, related to the human resource outcomes of labour turnover and absenteeism. Nor does the study find support for the argument that its use in conjunction with high involvement management enhances the performance effects of both. Equally, there is no support for the hypothesis from the institutional thesis that family-friendly management has positive effects on the legitimacy of the organization