Principles of meiotic chromosome assembly revealed in S. cerevisiae

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

Health care utilisation and problems in accessing health care of female undocumented immigrants in the Netherlands

Contains fulltext : 88419.pdf (publisher's version ) (Closed access)OBJECTIVE: To obtain information about the actual use of health care facilities by undocumented women and to identify obstacles they experience in accessing health care facilities. METHODS: A mixed methods study, with structured questionnaires and semi-structured interviews, was chosen to obtain a complete understanding. One-hundred undocumented women were recruited. Diversity was sought according to age, origin and reason for being undocumented. RESULTS: Undocumented female immigrants have unmet health care needs (56%) and low health care utilisation. Sixty-nine per cent of the women reported obstacles in accessing health care facilities. These included many personal obstacles such as shame, fear and/or lack of information. Poor language proficiency (OR 0.28;. CI 0.09-0.90) reduces utilisation of primary health care services. CONCLUSION: Health care utilisation of undocumented women is low. Undocumented women refrain from seeking health care because of personal obstacles. These women need to be identified and informed about their rights, the health care system and the duty of professional confidentiality of doctors. Finally, institutional obstacles to access care should be removed since they strengthen reluctance to seek help.1 oktober 201

Determinants of health care utilization by immigrants in Portugal

<p>Abstract</p> <p>Background</p> <p>The increasing diversity of population in European Countries poses new challenges to national health systems. There is a lack of data on accessibility and use of health care services by migrants, appropriateness of the care provided, client satisfaction and problems experienced when confronting the health care system. This limits knowledge about the multiple determinants of the utilization of health services. The aim of this study was to describe the access of migrants to health care and its determinants in Portugal.</p> <p>Methods</p> <p>The study sample included 1513 immigrants (53% men), interviewed at the National Immigrant Support Centre, in Lisbon. Data were collected using questionnaires. The magnitude of associations between use of National Health Service and socio-demographic variables was estimated by means of odds ratios (OR) at 95% confidence intervals, calculated using logistic regression.</p> <p>Results</p> <p>Among participants, 3.6% stated not knowing where to go if facing a health problem. Approximately 20% of the respondents reported that they had never used the National Health Service, men more than women. Among National Health Service users, 35.6% attended Health Centres, 12% used Hospital services, and 54.4% used both. Among the participants that ever used the health services, 22.4% reported to be unsatisfied or very unsatisfied. After adjusting for all variables, utilization of health services, among immigrant men, remained significantly associated with length of stay, legal status, and country of origin. Among immigrant women, the use of health services was significantly associated with length of stay and country of origin.</p> <p>Conclusion</p> <p>There is a clear need to better understand how to ensure access to health care services and to deliver appropriate care to immigrants, and that special consideration must be given to recent and undocumented migrants. To increase health services use, and the uptake of prevention programs, barriers must be identified and approaches to remove them developed, through coherent and comprehensive strategies.</p

Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase

Meiotic crossovers are produced when programmed double-strand breaks (DSBs) are repaired by recombination from homologous chromosomes (homologues). In a wide variety of organisms, meiotic HORMA-domain proteins are required to direct DSB repair towards homologues. This inter-homologue bias is required for efficient homology search, homologue alignment, and crossover formation. HORMA-domain proteins are also implicated in other processes related to crossover formation, including DSB formation, inhibition of promiscuous formation of the synaptonemal complex (SC), and the meiotic prophase checkpoint that monitors both DSB processing and SCs. We examined the behavior of two previously uncharacterized meiosis-specific mouse HORMA-domain proteins-HORMAD1 and HORMAD2-in wild-type mice and in mutants defective in DSB processing or SC formation. HORMADs are preferentially associated with unsynapsed chromosome axes throughout meiotic prophase. We observe a strong negative correlation between SC formation and presence of HORMADs on axes, and a positive correlation between the presumptive sites of high checkpoint-kinase ATR activity and hyper-accumulation of HORMADs on axes. HORMADs are not depleted from chromosomes in mutants that lack SCs. In contrast, DSB formation and DSB repair are not absolutely required for depletion of HORMADs from synapsed axes. A simple interpretation of these findings is that SC formation directly or indirectly promotes depletion of HORMADs from chromosome axes. We also find that TRIP13 protein is required for reciprocal distribution of HORMADs and the SYCP1/SC-component along chromosome axes. Similarities in mouse and budding yeast meiosis suggest that TRIP13/Pch2 proteins have a conserved role in establishing mutually exclusive HORMAD-rich and synapsed chromatin domains in both mouse and yeast. Taken together, our observations raise the possibility that involvement of meiotic HORMA-domain proteins in the regulation of homologue interactions is conserved in mammals

A High Throughput Genetic Screen Identifies New Early Meiotic Recombination Functions in Arabidopsis thaliana

Meiotic recombination is initiated by the formation of numerous DNA double-strand breaks (DSBs) catalysed by the widely conserved Spo11 protein. In Saccharomyces cerevisiae, Spo11 requires nine other proteins for meiotic DSB formation; however, unlike Spo11, few of these are conserved across kingdoms. In order to investigate this recombination step in higher eukaryotes, we took advantage of a high-throughput meiotic mutant screen carried out in the model plant Arabidopsis thaliana. A collection of 55,000 mutant lines was screened, and spo11-like mutations, characterised by a drastic decrease in chiasma formation at metaphase I associated with an absence of synapsis at prophase, were selected. This screen led to the identification of two populations of mutants classified according to their recombination defects: mutants that repair meiotic DSBs using the sister chromatid such as Atdmc1 or mutants that are unable to make DSBs like Atspo11-1. We found that in Arabidopsis thaliana at least four proteins are necessary for driving meiotic DSB repair via the homologous chromosomes. These include the previously characterised DMC1 and the Hop1-related ASY1 proteins, but also the meiotic specific cyclin SDS as well as the Hop2 Arabidopsis homologue AHP2. Analysing the mutants defective in DSB formation, we identified the previously characterised AtSPO11-1, AtSPO11-2, and AtPRD1 as well as two new genes, AtPRD2 and AtPRD3. Our data thus increase the number of proteins necessary for DSB formation in Arabidopsis thaliana to five. Unlike SPO11 and (to a minor extent) PRD1, these two new proteins are poorly conserved among species, suggesting that the DSB formation mechanism, but not its regulation, is conserved among eukaryotes

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans

Self-rated health and health problems of undocumented immigrant women in the Netherlands: a descriptive study.

Item does not contain fulltextIn this descriptive study, 100 female undocumented immigrants aged > or =18 years were interviewed about their health condition. The objective was to gain insight into the health situation and specific health problems of undocumented women. Sixty-five per cent of these undocumented women rated their health as 'poor' (moderate or bad) and 91 per cent spontaneously mentioned having current health problems. When provided with a list of 26 common health problems, subjects reported on average 11.1 complaints. Gynaecological and psychological complaints were very prevalent, but seldom mentioned spontaneously. Also obstetric problems were numerous. Undocumented women may not present important symptoms to physicians when they encounter them. We conclude that physicians should actively ask about psychological and gynaecological problems in this patient group. Special training on the health problems of undocumented female immigrants for health providers is recommended

Still a Hard-to-Reach Population? Using Social Media to Recuit Latino Gay Couples for an HIV Intervention Adaptation Study

Background Online social networking use has increased rapidly among African American and Latino men who have sex with men (MSM), making it important to understand how these technologies can be used to reach, retain, and maintain individuals in care and promote health wellness. In particular, the Internet is increasingly recognized as a platform for health communication and education. However, little is known about how primarily Spanish-speaking populations use and engage with each other through social media platforms. Objective We aimed to recruit eligible couples for a study to adapt “Connect ‘n Unite” (an HIV prevention intervention initially created for black gay couples) for Spanish-speaking Latino gay couples living in New York City. Methods In order to successfully design and implement an effective social media recruitment campaign to reach Spanish-speaking Latino gay couples for our ongoing “Latinos en Pareja” study, our community stakeholders and research team used McGuire’s communication/persuasion matrix. The matrix guided our research, specifically each marketing “channel”, targeted “message”, and target population or “receiver”. We developed a social media recruitment protocol and trained our research staff and stakeholders to conduct social media recruitment. Results As a result, in just 1 month, we recruited all of our subjects (N=14 couples, that is, N=28 participants) and reached more than 35,658 participants through different channels. One of the major successes of our social media recruitment campaign was to build a strong stakeholder base that became involved early on in all aspects of the research process—from pilot study writing and development to recruitment and retention. In addition, the variety of “messages” used across different social media platforms (including Facebook, the “Latinos en Pareja” study website, Craigslist, and various smartphone applications such as Grindr, SCRUFF, and Jack’d) helped recruit Latino gay couples. We also relied on a wide range of community-based organizations across New York City to promote the study and build in the social media components. Conclusions Our findings highlight the importance of incorporating communication technologies into the recruitment and engagement of participants in HIV interventions. Particularly, the success of our social media recruitment strategy with Spanish-speaking Latino MSM shows that this population is not particularly “hard to reach”, as it is often characterized within public health literature