The Specification and Global Reprogramming of Histone Epigenetic Marks during Gamete Formation and Early Embryo Development in C. elegans

In addition to the DNA contributed by sperm and oocytes, embryos receive parent-specific epigenetic information that can include histone variants, histone post-translational modifications (PTMs), and DNA methylation. However, a global view of how such marks are erased or retained during gamete formation and reprogrammed after fertilization is lacking. To focus on features conveyed by histones, we conducted a large-scale proteomic identification of histone variants and PTMs in sperm and mixed-stage embryo chromatin from C. elegans, a species that lacks conserved DNA methylation pathways. The fate of these histone marks was then tracked using immunostaining. Proteomic analysis found that sperm harbor ?2.4 fold lower levels of histone PTMs than embryos and revealed differences in classes of PTMs between sperm and embryos. Sperm chromatin repackaging involves the incorporation of the sperm-specific histone H2A variant HTAS-1, a widespread erasure of histone acetylation, and the retention of histone methylation at sites that mark the transcriptional history of chromatin domains during spermatogenesis. After fertilization, we show HTAS-1 and 6 histone PTM marks distinguish sperm and oocyte chromatin in the new embryo and characterize distinct paternal and maternal histone remodeling events during the oocyte-to-embryo transition. These include the exchange of histone H2A that is marked by ubiquitination, retention of HTAS-1, removal of the H2A variant HTZ-1, and differential reprogramming of histone PTMs. This work identifies novel and conserved features of paternal chromatin that are specified during spermatogenesis and processed in the embryo. Furthermore, our results show that different species, even those with diverged DNA packaging and imprinting strategies, use conserved histone modification and removal mechanisms to reprogram epigenetic information

Higher serum vitamin D levels are associated with decreased odds of obstructive lung disease in the general population: an NHANES analysis (2007–2008 to 2009–2010)

BackgroundObstructive lung disease is a significant cause of morbidity and healthcare burden within the USA. A growing body of evidence has suggested that vitamin D levels can influence the course or incidence of obstructive lung disease. However, there is an insufficient previous investigation of this association.Study design and methodsWe used the National Health and Nutrition Examination Survey (NHANES) cycles 2007-2008 and 2009-2010 spirometry results of individuals aged 40 years and older to assess the association between serum 25-hydroxyvitamin D levels and obstructive lung disease, as defined by the American Thoracic Society using the lower limit of normal. We used stage multivariate survey-logistic regression.ResultsThe final model included age, gender, body mass index, pack-years smoking history, season, income-to-poverty ratio and race/ethnicity. In the primary analysis using vitamin D as a continuous variable, there was no association between vitamin D levels and obstructive lung disease. We noted a trend between 'other Hispanic' self-identified race and serum vitamin D levels wherein higher levels were associated with higher odds of obstructive lung disease in this ethnicity, but not among other racial or ethnic groups (OR (95% CI)=1.40 (0.98 to 1.99), p=0.06). In a secondary analysis, when vitamin D was measured as a categorical variable, there was a significant association between the highest levels of serum vitamin D levels and lesser odds of obstructive lung disease (OR (95% CI)=0.77 [0.61 to 0.98], p=0.04).ConclusionsHigher serum vitamin D levels among adults are associated with decreased odds of obstructive lung disease in the general population. Results among non-Mexican Hispanic participants highlight the need for further research in minority populations. More work is needed to address the course and incidence of lung disease in the USA

Beta-blocker use in patients with chronic obstructive pulmonary disease: A systematic review: A systematic review of βB in COPD

Beta-blockers (βB) are a frequently used class of medications. Although βB have many indications, those related to cardiovascular disease are among the most common and important. However, in patients with chronic obstructive pulmonary disease (COPD), βB are used less often due to concerns about an unfavorable impact on respiratory morbidity and mortality. We performed a systematic review to assess the safety of βB in patients with COPD. We included a total of 2 randomized controlled trials and 28 observational studies. The majority found statistically significant reductions in mortality. The two higher quality observational studies reported increased mortality with βB. The risk of COPD exacerbations was reduced in about half of the studies. Nonetheless, there were significant biases that confounded the results. The highest quality RCT found a significant increase in severe and very severe COPD exacerbations with βB use. In conclusion, data on the safety of βB in patients with COPD are conflicting. However, given higher quality evidence showed harm with their use, βB should be prescribed with caution in patients with COPD, including patients with cardiac indication for βB

Risk of COPD exacerbation is increased by poor sleep quality and modified by social adversity.

Study objectivesSleep is an important dimension in the care of chronic obstructive pulmonary disease (COPD), but its relevance to exacerbations is unclear. We wanted to assess whether sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) is associated with an increased risk of COPD exacerbations and does this differ by socio-environmental exposures.MethodsWe included 1647 current and former smokers with spirometrically confirmed COPD from the SPIROMICS cohort. We assessed incidence rate ratios for exacerbation using zero-inflated negative binomial regression adjusting for demographics, medical comorbidities, and multiple metrics of disease severity, including respiratory medications, airflow obstruction, and symptom burden. Our final model adjusted for socio-environmental exposures using the Area Deprivation Index, a composite measure of contemporary neighborhood quality, and Adversity-Opportunity Index, a composite measure of individual-level historic and current socioeconomic indicators. We used a pre-determined threshold of 20% missingness to undertake multiple imputation by chained equations. As sensitivity analyses, we repeated models in those with complete data and after controlling for prior exacerbations. As an exploratory analysis, we considered an interaction between socio-environmental condition and sleep quality.ResultsAfter adjustment for all co-variates, increasing PSQI scores (range 0-21) were associated with a 5% increased risk for exacerbation per point (p = .001) in the imputed dataset. Sensitivity analyses using complete cases and after controlling for prior exacerbation history were similar. Exploratory analysis suggested less effect among those who lived in poor-quality neighborhoods (p-for-interaction = .035).ConclusionsPoor sleep quality may contribute to future exacerbations among patients with COPD. This represents one target for improving disease control.Clinical trial registrationSubpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). ClinicalTrials.gov Identifier# NCT01969344. Registry URL: https://clinicaltrials.gov/ct2/show/

Reconsidering the Utility of Race-Specific Lung Function Prediction Equations.

Rationale: African American individuals have worse outcomes in chronic obstructive pulmonary disease (COPD). Objectives: To assess whether race-specific approaches for estimating lung function contribute to racial inequities by failing to recognize pathological decrements and considering them normal. Methods: In a cohort with and at risk for COPD, we assessed whether lung function prediction equations applied in a race-specific versus universal manner better modeled the relationship between FEV1, FVC, and other COPD outcomes, including the COPD Assessment Test, St. George's Respiratory Questionnaire, computed tomography percent emphysema, airway wall thickness, and 6-minute-walk test. We related these outcomes to differences in FEV1 using multiple linear regression and compared predictive performance between fitted models using root mean squared error and Alpaydin's paired F test. Measurements and Main Results: Using race-specific equations, African American individuals were calculated to have better lung function than non-Hispanic White individuals (FEV1, 76.8% vs. 71.8% predicted; P = 0.02). Using universally applied equations, African American individuals were calculated to have worse lung function. Using Hankinson's Non-Hispanic White equation, FEV1 was 64.7% versus 71.8% (P < 0.001). Using the Global Lung Initiative's Other race equation, FEV1 was 70.0% versus 77.9% (P < 0.001). Prediction errors from linear regression were less for universally applied equations compared with race-specific equations when examining FEV1% predicted with the COPD Assessment Test (P < 0.01), St. George's Respiratory Questionnaire (P < 0.01), and airway wall thickness (P < 0.01). Although African American participants had greater adversity (P < 0.001), less adversity was only associated with better FEV1 in non-Hispanic White participants (P for interaction = 0.041). Conclusions: Race-specific equations may underestimate COPD severity in African American individuals.Clinical trial registered with www.clinicaltrials.gov (NCT01969344)

Race and Ethnicity in Pulmonary Function Test Interpretation: An Official American Thoracic Society Statement

Current American Thoracic Society (ATS) standards promote the use of race and ethnicity-specific reference equations for pulmonary function test (PFT) interpretation. There is rising concern that the use of race and ethnicity in PFT interpretation contributes to a false view of fixed differences between races and may mask the effects of differential exposures. This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation. The ATS convened a diverse group of clinicians and investigators for a workshop in 2021 to evaluate the use of race and ethnicity in PFT interpretation. Review of evidence published since then that challenges current practice and continued discussion concluded with a recommendation to replace race and ethnicity-specific equations with race-neutral average reference equations, which must be accompanied with a broader re-evaluation of how PFTs are used to make clinical, employment, and insurance decisions. There was also a call to engage key stakeholders not represented in this workshop and a statement of caution regarding the uncertain effects and potential harms of this change. Other recommendations include continued research and education to understand the impact of the change, to improve the evidence for the use of PFTs in general, and to identify modifiable risk factors for reduced pulmonary function

Preliminary Target Selection for the DESI Bright Galaxy Survey (BGS)

Abstract The Dark Energy Spectroscopic Instrument (DESI) will execute a nearly magnitude-limited survey of low redshift galaxies (0.05 ≤ z ≤ 0.4, median z ≈ 0.2). Clustering analyses of this Bright Galaxy Survey (BGS) will yield the most precise measurements to date of baryon acoustic oscillations and redshift-space distortions at low redshift. DESI BGS will comprise two target classes: (i) BRIGHT (r < 19.5 mag), and (ii) FAINT (19.5 < r < 20 mag). Here we present a summary of the star-galaxy separation, and different photometric and geometrical masks, used in BGS to reduce the number of spurious targets. The selection results in a total density of ∼800 objects deg−2 for the BRIGHT and ∼600 objects deg−2 for the FAINT selections. A full characterization of the BGS selection can be found in Ruiz-Macias et al

Contribution of Individual and Neighborhood Factors to Racial Disparities in Respiratory Outcomes.

Rationale: Black adults have worse health outcomes compared with white adults in certain chronic diseases, including chronic obstructive pulmonary disease (COPD).Objectives: To determine to what degree disadvantage by individual and neighborhood socioeconomic status (SES) may contribute to racial disparities in COPD outcomes.Methods: Individual and neighborhood-scale sociodemographic characteristics were determined in 2,649 current or former adult smokers with and without COPD at recruitment into SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). We assessed whether racial differences in symptom, functional, and imaging outcomes (St. George's Respiratory Questionnaire, COPD Assessment Test score, modified Medical Research Council dyspnea scale, 6-minute-walk test distance, and computed tomography [CT] scan metrics) and severe exacerbation risk were explained by individual or neighborhood SES. Using generalized linear mixed model regression, we compared respiratory outcomes by race, adjusting for confounders and individual-level and neighborhood-level descriptors of SES both separately and sequentially.Measurements and Main Results: After adjusting for COPD risk factors, Black participants had significantly worse respiratory symptoms and quality of life (modified Medical Research Council scale, COPD Assessment Test, and St. George's Respiratory Questionnaire), higher risk of severe exacerbations and higher percentage of emphysema, thicker airways (internal perimeter of 10 mm), and more air trapping on CT metrics compared with white participants. In addition, the association between Black race and respiratory outcomes was attenuated but remained statistically significant after adjusting for individual-level SES, which explained up to 12-35% of racial disparities. Further adjustment showed that neighborhood-level SES explained another 26-54% of the racial disparities in respiratory outcomes. Even after accounting for both individual and neighborhood SES factors, Black individuals continued to have increased severe exacerbation risk and persistently worse CT outcomes (emphysema, air trapping, and airway wall thickness).Conclusions: Disadvantages by individual- and neighborhood-level SES each partly explain disparities in respiratory outcomes between Black individuals and white individuals. Strategies to narrow the gap in SES disadvantages may help to reduce race-related health disparities in COPD; however, further work is needed to identify additional risk factors contributing to persistent disparities