Stretching the Rules: Monocentric Chromosomes with Multiple Centromere Domains

The centromere is a functional chromosome domain that is essential for faithful chromosome segregation during cell division and that can be reliably identified by the presence of the centromere-specific histone H3 variant CenH3. In monocentric chromosomes, the centromere is characterized by a single CenH3-containing region within a morphologically distinct primary constriction. This region usually spans up to a few Mbp composed mainly of centromere-specific satellite DNA common to all chromosomes of a given species. In holocentric chromosomes, there is no primary constriction; the centromere is composed of many CenH3 loci distributed along the entire length of a chromosome. Using correlative fluorescence light microscopy and high-resolution electron microscopy, we show that pea (Pisum sativum) chromosomes exhibit remarkably long primary constrictions that contain 3-5 explicit CenH3-containing regions, a novelty in centromere organization. In addition, we estimate that the size of the chromosome segment delimited by two outermost domains varies between 69 Mbp and 107 Mbp, several factors larger than any known centromere length. These domains are almost entirely composed of repetitive DNA sequences belonging to 13 distinct families of satellite DNA and one family of centromeric retrotransposons, all of which are unevenly distributed among pea chromosomes. We present the centromeres of Pisum as novel ``meta-polycentric'' functional domains. Our results demonstrate that the organization and DNA composition of functional centromere domains can be far more complex than previously thought, do not require single repetitive elements, and do not require single centromere domains in order to segregate properly. Based on these findings, we propose Pisum as a useful model for investigation of centromere architecture and the still poorly understood role of repetitive DNA in centromere evolution, determination, and function

School-based HPV vaccination positively impacts parents’ attitudes toward adolescent vaccination

Introduction This qualitative study aimed to explore parental attitudes, knowledge and decision-making about HPV vaccination for adolescents in the context of a gender-neutral school-based Australian National Immunisation Program (NIP). Methods Semi-structured interviews with parents of adolescents eligible for HPV vaccination were undertaken as part of an evaluation of a cluster-randomised controlled trial of a complex intervention in 40 schools (2013–2015). In this qualitative study, we purposively recruited a nested sample of parents from 11 schools across two Australian jurisdictions. Interviews explored parent knowledge and understanding of the HPV vaccine program; HPV vaccination decision-making; their adolescent’s knowledge about HPV vaccination; and their adolescent’s understanding about HPV vaccination, sexual awareness and behaviour. Transcripts were analysed using inductive and deductive thematic analysis. Results Parents’ of 22 adolescents had positive attitudes towards the program; the school-based delivery platform was the key driver shaping acceptance of and decision-making about HPV vaccination. They had difficulty recalling, or did not read, HPV vaccination information sent home. Some adolescents were involved in discussions about vaccination, with parents’ responsible for ultimate vaccine decision-making. All parents supported in-school education for adolescents about HPV and HPV vaccination. Parents’ knowledge about HPV vaccination was limited to cervical cancer and was largely absent regarding vaccination in males. Conclusions Parents’ positive attitudes towards the NIP and inclusion of the HPV vaccine is central to their vaccine decision-making and acceptance. More intensive communication strategies including school education opportunities are required to improve parents’ knowledge of HPV-related disease and to promote vaccine decision-making with adolescents

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Change and Aging Senescence as an adaptation

Understanding why we age is a long-lived open problem in evolutionary biology. Aging is prejudicial to the individual and evolutionary forces should prevent it, but many species show signs of senescence as individuals age. Here, I will propose a model for aging based on assumptions that are compatible with evolutionary theory: i) competition is between individuals; ii) there is some degree of locality, so quite often competition will between parents and their progeny; iii) optimal conditions are not stationary, mutation helps each species to keep competitive. When conditions change, a senescent species can drive immortal competitors to extinction. This counter-intuitive result arises from the pruning caused by the death of elder individuals. When there is change and mutation, each generation is slightly better adapted to the new conditions, but some older individuals survive by random chance. Senescence can eliminate those from the genetic pool. Even though individual selection forces always win over group selection ones, it is not exactly the individual that is selected, but its lineage. While senescence damages the individuals and has an evolutionary cost, it has a benefit of its own. It allows each lineage to adapt faster to changing conditions. We age because the world changes.Comment: 19 pages, 4 figure

Resolving the extragalactic hard X-ray background

The origin of the hard (2-10 keV) X-ray background has remained mysterious for over 35 years. Most of the soft (0.5-2 keV) X-ray background has been resolved into discrete sources, which are primarily quasars; however, these sources do not have the flat spectral shape required to match the X-ray background spectrum. Here we report the results of an X-ray survey 30 times more sensitive than previous studies in the hard band and four times more sensitive in the soft band. The sources detected in our survey account for at least 75 per cent of the hard X-ray background. The mean X-ray spectrum of these sources is in good agreement with that of the background. The X-ray emission from the majority of the detected sources is unambiguously associated with either the nuclei of otherwise normal bright galaxies or optically faint sources, which could either be active nuclei of dust enshrouded galaxies or the first quasars at very high redshifts.Comment: Nature article in pres

Observation of contemporaneous optical radiation from a gamma-ray burst

The origin of gamma-ray bursts (GRBs) has been enigmatic since their discovery. The situation improved dramatically in 1997, when the rapid availability of precise coordinates for the bursts allowed the detection of faint optical and radio afterglows - optical spectra thus obtained have demonstrated conclusively that the bursts occur at cosmological distances. But, despite efforts by several groups, optical detection has not hitherto been achieved during the brief duration of a burst. Here we report the detection of bright optical emission from GRB990123 while the burst was still in progress. Our observations begin 22 seconds after the onset of the burst and show an increase in brightness by a factor of 14 during the first 25 seconds; the brightness then declines by a factor of 100, at which point (700 seconds after the burst onset) it falls below our detection threshold. The redshift of this burst, approximately 1.6, implies a peak optical luminosity of 5 times 10^{49} erg per second. Optical emission from gamma-ray bursts has been generally thought to take place at the shock fronts generated by interaction of the primary energy source with the surrounding medium, where the gamma-rays might also be produced. The lack of a significant change in the gamma-ray light curve when the optical emission develops suggests that the gamma-rays are not produced at the shock front, but closer to the site of the original explosion.Comment: 10 pages, 2 figures. Accepted for publication in Nature. For additional information see http://www.umich.edu/~rotse

Reference Ranges for Bone Mineral Density and Prevalence of Osteoporosis in Vietnamese Men and Women

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the effect of different reference ranges in bone mineral density on the diagnosis of osteoporosis.</p> <p>Methods</p> <p>This cross-sectional study involved 357 men and 870 women aged between 18 and 89 years, who were randomly sampled from various districts within Ho Chi Minh City, Vietnam. BMD at the femoral neck, lumbar spine and whole body was measured by DXA (Hologic QDR4500). Polynomial regression models and bootstraps method were used to determine peak BMD and standard deviation (<it>SD</it>). Based on the two parameters, we computed T-scores (denoted by <it>T</it>_VN) for each individual in the study. A similar diagnosis was also done based on T-scores provided by the densitometer (<it>T</it>_DXA), which is based on the US White population (NHANES III). We then compared the concordance between <it>T</it>_VNand <it>T</it>_DXAin the classification of osteoporosis. Osteoporosis was defined according to the World Health Organization criteria.</p> <p>Results</p> <p>In post-menopausal women, the prevalence of osteoporosis based on femoral neck <it>T</it>_VNwas 29%, but when the diagnosis was based on <it>T</it>_DXA, the prevalence was 44%. In men aged 50+ years, the <it>T</it>_VN-based prevalence of osteoporosis was 10%, which was lower than <it>T</it>_DXA-based prevalence (30%). Among 177 women who were diagnosed with osteoporosis by <it>T</it>_DXA, 35% were actually osteopenia by <it>T</it>_VN. The kappa-statistic was 0.54 for women and 0.41 for men.</p> <p>Conclusion</p> <p>These data suggest that the <it>T-</it>scores provided by the Hologic QDR4500 over-diagnosed osteoporosis in Vietnamese men and women. This over-diagnosis could lead to over-treatment and influence the decision of recruitment of participants in clinical trials.</p

Attitudes towards chiropractic: an analysis of written comments from a survey of north american orthopaedic surgeons

<p>Abstract</p> <p>Background</p> <p>There is increasing interest by chiropractors in North America regarding integration into mainstream healthcare; however, there is limited information about attitudes towards the profession among conventional healthcare providers, including orthopaedic surgeons.</p> <p>Methods</p> <p>We administered a 43-item cross-sectional survey to 1000 Canadian and American orthopaedic surgeons that inquired about demographic variables and their attitudes towards chiropractic. Our survey included an option for respondants to include written comments, and our present analysis is restricted to these comments. Two reviewers, independantly and in duplicate, coded all written comments using thematic analysis.</p> <p>Results</p> <p>487 surgeons completed the survey (response rate 49%), and 174 provided written comments. Our analysis revealed 8 themes and 24 sub-themes represented in surgeons' comments. Reported themes were: variability amongst chiropractors (n = 55); concerns with chiropractic treatment (n = 54); areas where chiropractic is perceived as effective (n = 43); unethical behavior (n = 43); patient interaction (n = 36); the scientific basis of chiropractic (n = 26); personal experiences with chiropractic (n = 21); and chiropractic training (n = 18). Common sub-themes endorsed by surgeon's were diversity within the chiropractic profession as a barrier to increased interprofessional collaboration, endorsement for chiropractic treatment of musculoskeletal complaints, criticism for treatment of non-musculoskeletal complaints, and concern over whether chiropractic care was evidence-based.</p> <p>Conclusions</p> <p>Our analysis identified a number of issues that will have to be considered by the chiropractic profession as part of its efforts to further integrate chiropractic into mainstream healthcare.</p

Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of bronchial epithelium in COPD

<p>Abstract</p> <p>Background</p> <p>Cigarette smoke, the major risk factor for COPD, is known to activate matrix metalloproteinases in airway epithelium. We investigated whether metalloproteinases, particularly A Disintegrin and Metalloproteinase (ADAM)17, contribute to increased pro-inflammatory epithelial responses with respect to the release of IL-8 and TGF-α, cytokines implicated in COPD pathogenesis.</p> <p>Methods</p> <p>We studied the effects of cigarette smoke extract (CSE) and metalloproteinase inhibitors on TGF-α and IL-8 release in primary bronchial epithelial cells (PBECs) from COPD patients, healthy smokers and non-smokers.</p> <p>Results</p> <p>We observed that TGF-α was mainly shed by ADAM17 in PBECs from all groups. Interestingly, IL-8 production occurred independently from ADAM17 and TGF-α shedding, but was significantly inhibited by broad-spectrum metalloproteinase inhibitor TAPI-2. CSE did not induce ADAM17-dependent TGF-α shedding, while it slightly augmented the production of IL-8. This was accompanied by reduced endogenous inhibitor of metalloproteinase (TIMP)-3 levels, suggesting that CSE does not directly but rather indirectly alter activity of ADAM17 through the regulation of its endogenous inhibitor. Furthermore, whereas baseline TGF-α shedding was lower in COPD PBECs, the early release of IL-8 (likely due to its shedding) was higher in PBECs from COPD than healthy smokers. Importantly, this was accompanied by lower TIMP-2 levels in COPD PBECs, while baseline TIMP-3 levels were similar between groups.</p> <p>Conclusions</p> <p>Our data indicate that IL-8 secretion is regulated independently from ADAM17 activity and TGF-α shedding and that particularly its early release is differentially regulated in PBECs from COPD and healthy smokers. Since TIMP-2-sensitive metalloproteinases could potentially contribute to IL-8 release, these may be interesting targets to further investigate novel therapeutic strategies in COPD.</p

Social representations and the politics of participation

Recent work has called for the integration of different perspectives into the field of political psychology (Haste, 2012). This chapter suggests that one possible direction that such efforts can take is studying the role that social representations theory (SRT) can play in understanding political participation and social change. Social representations are systems of common-sense knowledge and social practice; they provide the lens through which to view and create social and political realities, mediate people's relations with these sociopolitical worlds and defend cultural and political identities. Social representations are therefore key for conceptualising participation as the activity that locates individuals and social groups in their sociopolitical world. Political participation is generally seen as conditional to membership of sociopolitical groups and therefore is often linked to citizenship. To be a citizen of a society or a member of any social group one has to participate as such. Often political participation is defined as the ability to communicate one's views to the political elite or to the political establishment (Uhlaner, 2001), or simply explicit involvement in politics and electoral processes (Milbrath, 1965). However, following scholars on ideology (Eagleton, 1991; Thompson, 1990) and social knowledge (Jovchelovitch, 2007), we extend our understanding of political participation to all social relations and also develop a more agentic model where individuals and groups construct, develop and resist their own views, ideas and beliefs. We thus adopt a broader approach to participation in comparison to other political-psychological approaches, such as personality approaches (e.g. Mondak and Halperin, 2008) and cognitive approaches or, more recently, neuropsychological approaches (Hatemi and McDermott, 2012). We move away from a focus on the individual's political behaviour and its antecedents and outline an approach that focuses on the interaction between psychological and political phenomena (Deutsch and Kinnvall, 2002) through examining the politics of social knowledge