SWI/SNF-like chromatin remodeling factor Fun30 supports point centromere function in S. cerevisiae

Budding yeast centromeres are sequence-defined point centromeres and are, unlike in many other organisms, not embedded in heterochromatin. Here we show that Fun30, a poorly understood SWI/SNF-like chromatin remodeling factor conserved in humans, promotes point centromere function through the formation of correct chromatin architecture at centromeres. Our determination of the genome-wide binding and nucleosome positioning properties of Fun30 shows that this enzyme is consistently enriched over centromeres and that a majority of CENs show Fun30-dependent changes in flanking nucleosome position and/or CEN core micrococcal nuclease accessibility. Fun30 deletion leads to defects in histone variant Htz1 occupancy genome-wide, including at and around most centromeres. FUN30 genetically interacts with CSE4, coding for the centromere-specific variant of histone H3, and counteracts the detrimental effect of transcription through centromeres on chromosome segregation and suppresses transcriptional noise over centromere CEN3. Previous work has shown a requirement for fission yeast and mammalian homologs of Fun30 in heterochromatin assembly. As centromeres in budding yeast are not embedded in heterochromatin, our findings indicate a direct role of Fun30 in centromere chromatin by promoting correct chromatin architecture

Title IX and Menstruation or Related Conditions

Title IX of the Education Amendments Act of 1972 (“Title IX”) prohibits sex discrimination in educational programs or activities receiving federal financial assistance. Neither the statute nor its implementing regulations explicitly define “sex” to include discrimination on the basis of menstruation or related conditions such as perimenopause and menopause. This textual absence has caused confusion over whether Title IX must be interpreted to protect students and other community members from all types of sex-based discrimination. It also calls into question the law\u27s ability to break down systemic sex-based barriers related to menstruation in educational spaces. Absent an interpretation that there is explicit Title IX coverage, menstruation will continue to cause some students to miss instruction. Other students may be denied access to a menstrual product or a restroom as needed and face health consequences. They also may be teased and bullied after menstrual blood visibly leaks onto their clothes. Employees, who are also covered by Title IX, may be fired for damaging school property as a result of such leaks. People in perimenopause may be denied reasonable modifications like bathroom access, water, or temperature control. Collectively, this creates an educational system that prevents students, faculty, or employees from fully participating in educational institutions and causes harm. On July 12, 2022, the U.S. Department of Education (“DOE”) issued a Notice of Proposed Rulemaking “to better align the Title IX regulatory requirements with Title IX\u27s nondiscrimination mandate, and to clarify the scope and application of Title IX and [schools\u27 obligations] to provide an educational environment free from discrimination on the basis of sex, including through responding to incidents of sex discrimination.” On September 12, 2022, the Authors submitted the below Comment asking the DOE to modify existing regulations to cover menstruation-related discrimination in three ways. First, the regulations should include “menstruation or related conditions” from menarche through menopause in the scope of discrimination on the basis of sex. Second, the regulations should include reasonable modifications for “menstruation or related conditions.” Finally, the regulations should provide education on “menstruation or related conditions” to all students and employees, regardless of sex, to tackle barriers related to reporting and eliminating sex-based discrimination and to provide equal access. Only then will Title IX be able to fully live up to its nondiscrimination mandate. This Article contains our Comment asking the DOE to make these changes and explicitly include menstruation or related conditions in Title IX\u27s protections. In addition to our Comment, over 150 of the publicly available rulemaking submissions referenced menstruation and over thirty-five mentioned menopause. Collectively, these comments--from other academics, public health scholars, medical practitioners, clinicians, advocates, and individuals--further demonstrate the need for Title IX to cover menstruation-related discrimination

Genome-wide chromatin mapping with size resolution reveals a dynamic sub-nucleosomal landscape in Arabidopsis

All eukaryotic genomes are packaged as chromatin, with DNA interlaced with both regularly patterned nucleosomes and sub-nucleosomal-sized protein structures such as mobile and labile transcription factors (TF) and initiation complexes, together forming a dynamic chromatin landscape. Whilst details of nucleosome position in Arabidopsis have been previously analysed, there is less understanding of their relationship to more dynamic sub-nucleosomal particles (subNSPs) defined as protected regions shorter than the ~150bp typical of nucleosomes. The genome-wide profile of these subNSPs has not been previously analysed in plants and this study investigates the relationship of dynamic bound particles with transcriptional control. Here we combine differential micrococcal nuclease (MNase) digestion and a modified paired-end sequencing protocol to reveal the chromatin structure landscape of Arabidopsis cells across a wide particle size range. Linking this data to RNAseq expression analysis provides detailed insight into the relationship of identified DNA-bound particles with transcriptional activity. The use of differential digestion reveals sensitive positions, including a labile -1 nucleosome positioned upstream of the transcription start site (TSS) of active genes. We investigated the response of the chromatin landscape to changes in environmental conditions using light and dark growth, given the large transcriptional changes resulting from this simple alteration. The resulting shifts in the suites of expressed and repressed genes show little correspondence to changes in nucleosome positioning, but led to significant alterations in the profile of subNSPs upstream of TSS both globally and locally. We examined previously mapped positions for the TFs PIF3, PIF4 and CCA1, which regulate light responses, and found that changes in subNSPs co-localized with these binding sites. This small particle structure is detected only under low levels of MNase digestion and is lost on more complete digestion of chromatin to nucleosomes. We conclude that wide-spectrum analysis of the Arabidopsis genome by differential MNase digestion allows detection of sensitive features hereto obscured, and the comparisons between genome-wide subNSP profiles reveals dynamic changes in their distribution, particularly at distinct genomic locations (i.e. 5’UTRs). The method here employed allows insight into the complex influence of genetic and extrinsic factors in modifying the sub-nucleosomal landscape in association with transcriptional changes

Evaluating the impact of an intervention to increase uptake of modern contraceptives among adolescent girls (15-19 years) in Nigeria, Ethiopia and Tanzania: the Adolescents 360 quasi-experimental study protocol.

INTRODUCTION: Nigeria, Ethiopia and Tanzania have some of the highest teenage pregnancy rates and lowest rates of modern contraceptive use among adolescents. The transdisciplinary Adolescents 360 (A360) initiative being rolled out across these three countries uses human-centred design to create context-specific multicomponent interventions with the aim of increasing voluntary modern contraceptive use among girls aged 15-19 years. METHODS: The primary objective of the outcome evaluation is to assess the impact of A360 on the modern contraceptive prevalence rate (mCPR) among sexually active girls aged 15-19 years. A360 targets different subpopulations of adolescent girls in the three countries. In Northern Nigeria and Ethiopia, the study population is married girls aged 15-19 years. In Southern Nigeria, the study population is unmarried girls aged 15-19 years. In Tanzania, both married and unmarried girls aged 15-19 years will be included in the study. In all settings, we will use a prepopulation and postpopulation-based cross-sectional survey design. In Nigeria, the study design will also include a comparison group. A one-stage sampling design will be used in Nigeria and Ethiopia. A two-stage sampling design will be used in Tanzania. Questionnaires will be administered face-to-face by female interviewers aged between 18 and 26 years. Study outcomes will be assessed before the start of A360 implementation in late 2017 and approximately 24 months after implementation in late 2019. ETHICS AND DISSEMINATION: Findings of this study will be widely disseminated through workshops, conference presentations, reports, briefings, factsheets and academic publications

Author Correction: A population-specific reference panel empowers genetic studies of Anabaptist populations.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper

Management of Obstructive Sleep Apnea and Comorbid Insomnia: A Mixed-Methods Evaluation

The purpose of this study was to examine the process of care in an interdisciplinary sleep clinic for patients with obstructive sleep apnea (OSA) and comorbid insomnia. A mixed-methods approach was used to examine clinical and patient-centered measures for 34 patients who received positive-airway pressure for OSA or cognitive-behavior therapy for insomnia. The results revealed baseline-to-follow-up improvements on several self-reported sleep parameters and measures of daytime functioning. Qualitative analyses from patient interviews revealed three themes: conceptual distinctions about each sleep disorder, importance of treating both sleep disorders, and preferences with regard to the sequence of treatment. These findings indicate that patients with OSA and comorbid insomnia encounter unique challenges. A dimensional approach to assessment and treatment is proposed for future research

Blood pressure self-monitoring in pregnancy (BuMP) feasibility study; a qualitative analysis of women's experiences of self-monitoring

Background Hypertensive disorders in pregnancy are a leading cause of maternal and fetal morbidity worldwide. Raised blood pressure (BP) affects 10% of pregnancies worldwide, of which almost half develop pre-eclampsia. The proportion of pregnant women who have risk factors for pre-eclampsia (such as pre-existing hypertension, obesity and advanced maternal age) is increasing. Pre-eclampsia can manifest itself before women experience symptoms and can develop between antenatal visits. Incentives to improve early detection of gestational hypertensive disorders are therefore strong and self-monitoring of blood pressure (SMBP) in pregnancy might be one means to achieve this, whilst improving women’s involvement in antenatal care. The Blood Pressure Self-Monitoring in Pregnancy (BuMP) study aimed to evaluate the feasibility and acceptability of SMBP in pregnancy. Methods To understand women’s experiences of SMBP during pregnancy, we undertook a qualitative study embedded within the BuMP observational feasibility study. Women who were at higher risk of developing hypertension and/or pre-eclampsia were invited to take part in a study using SMBP and also invited to take part in an interview. Semi-structured interviews were conducted at the women’s homes in Oxfordshire and Birmingham with women who were self-monitoring their BP as part of the BuMP feasibility study in 2014. Interviews were conducted by a qualitative researcher and transcribed verbatim. A framework approach was used for analysis. Results Fifteen women agreed to be interviewed. Respondents reported general willingness to engage with monitoring their own BP, feeling that it could reduce anxiety around their health during pregnancy, particularly if they had previous experience of raised BP or pre-eclampsia. They felt able to incorporate self-monitoring into their weekly routines, although this was harder post-partum. Self-monitoring of BP made them more aware of the risks of hypertension and pre-eclampsia in pregnancy. Feelings of reassurance and empowerment were commonly reported by the women in our sample

New Phase-coherent Measurements of Pulsar Braking Indices

Pulsar braking indices offer insight into the physics that underlies pulsar spin-down. Only five braking indices have been measured via phase-coherent timing; all measured values are less than 3, the value expected from magnetic dipole radiation. Here we present new measurements for three of the five pulsar braking indices, obtained with phase-coherent timing for PSRs J1846-0258 (n=2.65+/-0.01), B1509-58 (n=2.839+/-0.001) and B0540-69 (n=2.140+/-0.009). We discuss the implications of these results and possible physical explanations for them.Comment: 7 pages, 5 figures. To be published in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 24-28, 2006, London, UK), eds. D. Page, R. Turolla, & S. Zan

Blood pressure self-monitoring in pregnancy: examining feasibility in a prospective cohort study

Background: Raised blood pressure (BP) affects approximately 10% of pregnancies worldwide, and a high proportion of affected women develop pre-eclampsia. This study aimed to evaluate the feasibility of self-monitoring of BP in pregnancy in women at higher risk of pre-eclampsia. Methods: This prospective cohort study of self-monitoring BP in pregnancy was carried out in two hospital trusts in Birmingham and Oxford and thirteen primary care practices in Oxfordshire. Eligible women were those defined by the UK National Institute for Health and Care Excellence (NICE) guidelines as at higher risk of pre-eclampsia. A total of 201 participants were recruited between 12 and 16 weeks of pregnancy and were asked to take two BP readings twice daily three times a week through their pregnancy. Primary outcomes were recruitment, retention and persistence of self-monitoring. Study recruitment and retention were analysed with descriptive statistics. Survival analysis was used to evaluate the persistence of self-monitoring and the performance of self-monitoring in the early detection of gestational hypertension, compared to clinic BP monitoring. Secondary outcomes were the mean clinic and self-monitored BP readings and the performance of self-monitoring in the detection of gestational hypertension and pre-eclampsia compared to clinic BP. Results: Of 201 women recruited, 161 (80%) remained in the study at 36 weeks or to the end of their pregnancy, 162 (81%) provided any home readings suitable for analysis, 148 (74%) continued to self-monitor at 20 weeks and 107 (66%) at 36 weeks. Self-monitored readings were similar in value to contemporaneous matched clinic readings for both systolic and diastolic BP. Of the 23 who developed gestational hypertension or pre-eclampsia and self-monitored, 9(39%) had a raised home BP prior to a raised clinic BP. Conclusions: Self-monitoring of BP in pregnancy is feasible and has potential to be useful in the early detection of gestational hypertensive disorders but maintaining self-monitoring throughout pregnancy requires support and probably enhanced training