Lung cancer screening provider recommendation and completion in black and White patients with a smoking history in two healthcare systems: a survey study.

BACKGROUND: Annual lung cancer screening (LCS) with low dose CT reduces lung cancer mortality. LCS is underutilized. Black people who smoke tobacco have high risk of lung cancer but are less likely to be screened than are White people. This study reports provider recommendation and patient completion of LCS and colorectal cancer screening (CRCS) among patients by race to assess for utilization of LCS. METHODS: 3000 patients (oversampled for Black patients) across two healthcare systems (in Rhode Island and Minnesota) who had a chart documented age of 55 to 80 and a smoking history were invited to participate in a survey about cancer screening. Logistic regression analysis compared the rates of recommended and received cancer screenings. RESULTS: 1177 participants responded (42% response rate; 45% White, 39% Black). 24% of respondents were eligible for LCS based on USPSTF2013 criteria. One-third of patients eligible for LCS reported that a doctor had recommended screening, compared to 90% of patients reporting a doctor recommended CRCS. Of those recommended screening, 88% reported completing LCS vs. 83% who reported completion of a sigmoidoscopy/colonoscopy. Black patients were equally likely to receive LCS recommendations but less likely to complete LCS when referred compared to White patients. There was no difference in completion of CRCS between Black and White patients. CONCLUSIONS: Primary care providers rarely recommend lung cancer screening to patients with a smoking history. Systemic changes are needed to improve provider referral for LCS and to facilitate eligible Black people to complete LCS.

Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of stem cell maintenance and neuronal differentiation.

Development of embryonic stem cells (ESCs) into neurons requires intricate regulation of transcription, splicing, and translation, but how these processes interconnect is not understood. We found that polypyrimidine tract binding protein 1 (PTBP1) controls splicing of DPF2, a subunit of BRG1/BRM-associated factor (BAF) chromatin remodeling complexes. Dpf2 exon 7 splicing is inhibited by PTBP1 to produce the DPF2-S isoform early in development. During neuronal differentiation, loss of PTBP1 allows exon 7 inclusion and DPF2-L expression. Different cellular phenotypes and gene expression programs were induced by these alternative DPF2 isoforms. We identified chromatin binding sites enriched for each DPF2 isoform, as well as sites bound by both. In ESC, DPF2-S preferential sites were bound by pluripotency factors. In neuronal progenitors, DPF2-S sites were bound by nuclear factor I (NFI), while DPF2-L sites were bound by CCCTC-binding factor (CTCF). DPF2-S sites exhibited enhancer modifications, while DPF2-L sites showed promoter modifications. Thus, alternative splicing redirects BAF complex targeting to impact chromatin organization during neuronal development.

The transcription factor NF-κB orchestrates nucleosome remodeling during the primary response to Toll-like receptor 4 signaling.

Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed to define the identities of the transcription factors that promote TLR-induced remodeling. An analysis strategy based on ATAC-seq and single-cell ATAC-seq that enriched for genomic regions most likely to undergo remodeling revealed that the transcription factor nuclear factor κB (NF-κB) bound to all high-confidence peaks marking remodeling during the primary response to the TLR4 ligand, lipid A. Deletion of NF-κB subunits RelA and c-Rel resulted in the loss of remodeling at high-confidence ATAC-seq peaks, and CRISPR-Cas9 mutagenesis of NF-κB-binding motifs impaired remodeling. Remodeling selectivity at defined regions was conferred by collaboration with other inducible factors, including IRF3- and MAP-kinase-induced factors. Thus, NF-κB is unique among TLR4-activated transcription factors in its broad contribution to inducible nucleosome remodeling, alongside its ability to activate poised enhancers and promoters assembled into open chromatin.

Temporal regulation of head-on transcription at replication initiation sites.

Head-on (HO) collisions between the DNA replication machinery and RNA polymerase over R-loop forming sequences (RLFS) are genotoxic, leading to replication fork blockage and DNA breaks. Current models suggest that HO collisions are avoided through replication initiation site (RIS) positioning upstream of active genes, ensuring co-orientation of replication fork movement and genic transcription. However, this model does not account for pervasive transcription, or intragenic RIS. Moreover, pervasive transcription initiation and CG-rich DNA is a feature of RIS, suggesting that HO transcription units (HO TUs) capable of forming R-loops might occur. Through mining phased GRO-seq data, and developing an informatics strategy to stringently identify RIS, we demonstrate that HO TUs containing RLFS occur at RIS in MCF-7 cells, and are downregulated at the G1/S phase boundary. Our analysis reveals a novel spatiotemporal relationship between transcription and replication, and supports the idea that HO collisions are avoided through transcriptional regulatory mechanisms.

Delayed onset phlegmasia cerulea dolens post-SARS-CoV-2 infection treated with minimally invasive clot retrieval technology.

Coronavirus disease 2019 is associated with a significant venous thromboembolic risk. Phlegmasia cerulean dolens is a severe form of deep vein thrombosis that can lead to acute limb ischemia. In this report, we present a 58-year-old woman who developed a delayed-onset left lower extremity phlegmasia cerulean dolens 8 weeks after coronavirus disease 2019 onset that led to compartment syndrome and acute limb ischemia from external compression of the arterial vasculature from edematous muscle. The patient received an emergent minimally invasive percutaneous mechanical thrombectomy and four-compartment fasciotomy, resulting in adequate perfusion and ultimately made a full recovery.

Resistance training for Black men with depressive symptoms: a pilot randomized controlled trial to assess acceptability, feasibility, and preliminary efficacy.

BACKGROUND: Depression is under-recognized in Black men, who are less likely to seek or have access to psychiatric treatment. Resistance training (RT; i.e., weight lifting) can improve depressive symptoms and may be more acceptable to Black men, but its effects have not been examined for Black men with depressive symptoms. METHODS: Fifty Black men with depressive symptoms were randomized to either (a) 12 weeks of RT (coupled with Behavioral Activation techniques to promote adherence) or (b) an attention-control group (Health, Wellness, and Education; HWE). Both groups met twice/week for 12 weeks, and follow-up assessments were done at end-of-treatment (EOT) and 6 months after enrollment. Changes in physical activity and muscular strength were collected as a manipulation check. The primary outcome was interviewer assessed symptoms of depression using the Quick Inventory of Depression Symptomology (QIDS). Secondary outcomes included self-reported depressive symptoms, anxiety, and stress. The association between change in QIDS from baseline to EOT and concurrent changes in physical activity and muscular strength in the RT group were explored as an initial assessment of mechanism. Longitudinal mixed effects regression models with subject-specific intercepts were used to examine intervention effects. RESULTS: A sample with high rates of medical comorbidities (e.g., 44% HIV positive), substance use (e.g., 34% smoking), and negative social determinates of health (e.g., 50% unemployed) was enrolled. Recruitment, engagement, and retention data indicate that the intervention and design were feasible. The RT group showed greater gains in self-reported exercise (b = 270.94, SE = 105.69, p = .01) and muscular strength (b = 11.71, SE = 4.23, p = .01 for upper body and b = 4.24, SE = 2.02, p = .04 for lower body) than the HWE group. The RT group had greater reductions in QIDS scores at both EOT (b = -3.00, SE = 1.34, p = .01) and 6 months (b = -2.63, SE = 1.81, p = .04). The RT group showed a greater reduction in anxiety at EOT (b = -2.67, SE = 1.06, p = .02). Findings regarding self-reported depressive symptoms and stress were non-significant, but in the expected direction with effect sizes in the small to medium range. In the RT group, improvement on the QIDS between baseline and EOT was associated with concurrent improvements in physical activity (b = 21.03, SE = 11.16, p = .02) and muscular strength (b = 1.27, SE = .44, p = .03 for upper body and b = .75, SE = .14, p = .03 for lower body). CONCLUSIONS: Results suggest that RT is feasible and may be efficacious for reducing depressive symptoms among underserved urban Black men. TRIAL REGISTRATION: ClinicalTrial.gov #: NCT03107039 (Registered 11/04/2017).

Intersections between Young Women's Racial/Ethnic Identities and Sexual Orientation on Rates of Sexual Violence and Substance Use.

BACKGROUND: Little is known about whether there are differences in rates of sexual violence and its association with substance use based on women's identities, specifically the intersection of their race/ethnicity and sexual orientation. METHOD: Women (N = 546; 18 to 29 years of age) recruited from a reproductive healthcare clinic reported their race, ethnicity, sexual orientation, sexual violence history and substance use. Five logistic regressions examined (a) rates of sexual violence, and (b) the strength of the associations between sexual violence and four substance use outcomes (heavy alcohol use, marijuana use, cigarette use, number of cigarettes used) based on sexual orientation. Subsequent logistic regressions examined race/ethnicity as a moderator of the associations between sexual orientation and (a) rates of sexual violence and (b) substance use. RESULTS: Most women surveyed were heterosexual (64%), and 35% of all women reported unwanted sex. Sexual minority women (SMW) reported higher rates of sexual violence and substance use than heterosexual women. Sexual violence was more strongly associated with heavy alcohol use, but not with marijuana or cigarette use, for SMW than heterosexual women. Rates of sexual violence varied based on the intersection of sexual orientation and race/ethnicity. Although SMW were more likely to report sexual violence than heterosexual women, this association was weaker for Black/Latinx women than for non-Hispanic White women (aOR = 0.39, 95%CI [0.18, 0.82]). Race/ethnicity did not moderate the strength of associations between sexual violence and substance use. CONCLUSIONS: SMW exhibit increased risk for sexual violence and substance use, and victimization was associated with heavy alcohol use. Few racial/ethnic differences emerged as a function of sexual orientation, so SMW are a group with unique needs around sexual violence experiences and substance use, regardless of race/ethnicity. Healthcare providers should be aware of the link between substance use and prior victimization when treating SMW.

Limited Ability of Three Health Literacy Screening Items to Identify Adult English- and Spanish-Speaking Emergency Department Patients With Lower Health Literacy.

STUDY OBJECTIVE: Brief, easily administered, and valid health literacy assessment tools are needed to optimize health care delivery in the emergency medicine setting. Three health literacy screening items have been proposed to assess health literacy in outpatient settings. We investigated their ability to identify English- and Spanish-speaking adult emergency department (ED) patients with lower health literacy. METHODS: Participants were Spanish- or English-speaking adult patients randomly selected from 4 geographically spread, US, urban, safety-net EDs. Participants completed the 3 health literacy screening items, as well as the Short Assessment of Health Literacy-Spanish and English (SAHL-S&E). Test performance characteristics, including receiver operating characteristics area under the curve, of the 3 health literacy screening items were estimated, as compared with the SAHL-S&E. RESULTS: According to the SAHL-S&E, 36% of the 1,165 English speakers and 35% of the 1,605 Spanish speakers had lower health literacy. Areas under the curve for each health literacy screening item individually were: needing others to help read materials (English 0.59, 95% confidence interval [CI] 0.56 to 0.62; Spanish 0.58, 95% CI 0.56 to 0.61), problems learning because of difficulty reading (English 0.63, 95% CI 0.60 to 0.66; Spanish 0.59, 95% CI 0.56 to 0.62), and confidence with completing forms (English 0.62, 95% CI 0.59 to 0.65; Spanish 0.60, 95% CI 0.57 to 0.63). Areas under the curve for the 3 screening items combined were: English 0.66 (95% CI 0.63 to 0.70) and Spanish 0.62 (95% CI 0.59 to 0.64). CONCLUSION: The 3 health literacy screening items performed poorly in identifying adult ED patients with lower health literacy. Higher-validity screening measures are needed to better serve the health care needs of this vulnerable population in the ED setting.

Waterpipe (hookah) tobacco use in pregnancy: use, preferences and perceptions of flavours.

OBJECTIVE: Waterpipe tobacco (WPT; hookah) use is common in pregnant and reproductive-age women. Sweet flavours contribute to the appeal of WPT and are a potential regulatory target. This study investigated use, preferences and perceptions of WPT flavours in pregnant WPT users, and the impact of flavour preferences on preconception/prenatal WPT use and exposure biomarkers. METHODS: 58 pregnant WPT users (mean age=27 years) completed a detailed interview regarding their WPT flavours use, preferences and perceptions. Biomarkers of nicotine and carcinogen exposure (eg, cotinine, benzene, butadiene) were also collected. RESULTS: 55% of participants were dual/poly WPT users (ie, reported use of one or more other tobacco products in addition to WPT). Pregnant WPT users reported nearly exclusive use of flavoured WPT, with greater use of menthol/mint (68%) followed by fruit flavours (48%) (p<0.001), and greater preferences for fruit followed by menthol/mint flavours (ps<0.05). Harm perceptions did not differ among flavours. Compared with dual/poly WPT users, WPT-only users reported more total WPT use events, greater use of and preference for menthol/mint flavoured WPT (ps<0.001), and decreased exposure biomarkers (ps≤0.040). Preference for menthol/mint and fruit flavours predicted more flavoured WPT use events during preconception and pregnancy; preference for menthol/mint predicted detectable cotinine and benzene levels but not butadiene. CONCLUSIONS: This is the first study of WPT flavour use, preferences and perceptions in pregnant women. Use of and preference for menthol/mint and fruit WPT flavours in this vulnerable population could be considered in regulating WPT flavours to protect the health of women and children.

HIV testing intentions and behaviors among 14-17-year-old sexual minority males.

Adolescent sexual minority males have low rates of HIV testing despite increased risk for HIV acquisition. This study will examine adolescent sexual minority males' (a) HIV testing behaviors and intentions, and (b) associations with disclosure to healthcare providers of male-male attraction. Sexual minority males were recruited using social media sites to obtain a national sample. Participants (N = 207) were 14-17-year-old cisgender males living in the U.S. who (1) self-identified as gay/bisexual, (2) reported sexual attraction to males, or (3) reported past-year voluntary sexual contact with a male. Only 14% of participants reported they had tested for HIV, even though 20% reported a history of condomless anal intercourse with male partners. Three-quarters (77%) planned to test for HIV, but only 48% planned to test annually (i.e., current CDC recommendation). Only 20% of participants had disclosed male-male attraction to their healthcare provider, but adolescents who disclosed had five times the odds of testing for HIV (AOR = 5.40). Rates of HIV testing and disclosure of male-male interests to a healthcare provider are low among adolescent sexual minority males. Given the association between disclosure and HIV testing, creating non-judgmental healthcare settings and optimizing patient-provider communication are likely to improve uptake of HIV testing by at-risk youth.

Sexual risk behavior and substance use among young, diverse women seeking care at a reproductive health clinic.

BACKGROUND: To describe sexual risk behavior, alcohol (and other substance) use, and perceived health promotion needs among young adult women seeking care from an urban reproductive health care clinic in the Northeastern United States, and to examine if these needs differ by race and ethnicity. METHODS: Women 18-29 years old presenting for a routine medical visit were invited to participate. Of 486 eligible women, 466 (96%) agreed to participate and completed a brief survey on a tablet computer. Most of the sample (53%) identified as non-Hispanic White. One-quarter (25%) identified as Hispanic/Latina. A smaller proportion of women identified as African American (19%). RESULTS: One-third (31%) of women reported a history of sexually transmitted infection (STI), and women reported infrequent condom use with recent sexual partners. Regarding behavioral health needs, nearly three-quarters of women (72%) reported regular alcohol use, approximately one-third had used marijuana (37%) or tobacco (33%) in the last month, and 19% reported clinically significant depressive symptoms in the last two weeks. Women reported moderate-to-strong interest in receiving information about relationships and sexual health; however, the majority were not interested in information about their substance use. Hispanic and African-American women were more likely to report STI history despite reporting fewer sexual partners than non-Hispanic White women. Minority women also reported significantly less alcohol and cigarette use, but more water pipe tobacco use, and reported significantly greater interest in interventions to promote sexual health. Hispanic women also evidenced significantly elevated rates of depressive symptoms, with 26% of Hispanic women reporting a clinically significant level of depressive symptoms. CONCLUSIONS: Reproductive health centers are opportune settings to address a broad range of healthcare needs, including sexual health, substance use, and mental health. These centers engage a diverse group of women, which is important given observed disparities in health outcomes based on race/ethnicity. Young women, particularly racial and ethnic minority women, report the most interest in services addressing sexual and relationship health.

Promoter-Enhancer Communication Occurs Primarily within Insulated Neighborhoods.

Metazoan chromosomes are sequentially partitioned into topologically associating domains (TADs) and then into smaller sub-domains. One class of sub-domains, insulated neighborhoods, are proposed to spatially sequester and insulate the enclosed genes through self-association and chromatin looping. However, it has not been determined functionally whether promoter-enhancer interactions and gene regulation are broadly restricted to within these loops. Here, we employed published datasets from murine embryonic stem cells (mESCs) to identify insulated neighborhoods that confine promoter-enhancer interactions and demarcate gene regulatory regions. To directly address the functionality of these regions, we depleted estrogen-related receptor ß (Esrrb), which binds the Mediator co-activator complex, to impair enhancers of genes within 222 insulated neighborhoods without causing mESC differentiation. Esrrb depletion reduces Mediator binding, promoter-enhancer looping, and expression of both nascent RNA and mRNA within the insulated neighborhoods without significantly affecting the flanking genes. Our data indicate that insulated neighborhoods represent functional regulons in mammalian genomes.

Racial Disparities in Lung Cancer Screening: An Exploratory Investigation.

BACKGROUND/PURPOSE: Lung cancer is the leading cause of cancer death in the United States. Black Americans have the highest rate of lung cancer mortality, due to being diagnosed at later stage. Lung Cancer Screening (LCS) facilitates earlier detection and has been associated with a reduction in cancer death. We investigated LCS utilization and explored racial disparities (Black vs. non-Black) in LCS among patients for whom LCS is clinically indicated. METHODS: Using electronic medical records from the Lifespan Medical System, we randomly selected 200 patients who were likely to meet U. S. Preventive Services Taskforce (USPSTF) guidelines for LCS and mailed each patient a survey to assess LCS eligibility and uptake. RESULTS: Nearly three-quarters (n = 146, 73%) completed the survey and, of survey respondents, 92% (n = 134) were eligible for the study. Among eligible patients, 35% met criteria for LCS; non-Black patients were 90% more likely to meet criteria for LCS than Black patients (44% vs. 27%). Of the patients meeting USPSTF criteria, only 21% reported being screened; eligible non-Black patients were 2.8 times more likely to have had LCS than eligible Black patients (30% vs. 12%). CONCLUSIONS: LCS utilization is low despite coverage provided through the Affordable Care Act. Black patients are less likely to qualify for screening and disproportionately less likely to be screened for lung cancer compared with non-Black patients. Targeted intervention strategies are needed to increase referral for and uptake of LCS in patients who are at high risk for developing lung cancer, and for Black patients in particular.

Correlates of Never Testing for HIV Among Sexually Active Internet-Recruited Gay, Bisexual, and Other Men Who Have Sex with Men in the United States.

In the United States, gay, bisexual, and other men who have sex with men (GBMSM) are disproportionately affected by the HIV/AIDS epidemic. Despite great strides in HIV prevention, including biobehavioral HIV prevention strategies such as pre-exposure prophylaxis and treatment as prevention, there has been relatively low uptake of these strategies. The success of biobehavioral prevention strategies requires HIV testing but a subset of GBMSM have never been tested. To optimize prevention efforts, we sought to understand the characteristics of GBMSM who report never testing for HIV. A sample of GBMSM was recruited online in 2012 to complete a cross-sectional survey of sexual behavior and sexual health. Bivariate and multivariable analyses were used to identify characteristics of "never testing for HIV." Of the 1170 participants, 151 (13%) reported never testing for HIV. In multivariable analyses, younger age, less education, endorsing a non-gay sexual identity, living in rural areas, not having a primary partner, living in unstable housing, and reporting regular condom use during anal sex were independently associated with never testing. We conclude that, despite a substantial focus on HIV testing among GBMSM in the United States, a proportion of sexually active, adult GBMSM report never having tested for HIV in their lifetimes. The current study illustrates the importance of addressing individual and structural factors that serve as barriers to HIV testing among GBMSM. Addressing these barriers will improve access to HIV testing and other biobehavioral HIV prevention strategies and, ultimately, alleviate disparities in HIV/AIDS in the United States.

A comparison of the effects of lindane and FeCl3/ADP on spontaneous contractions in isolated rat or human term myometrium.

Oxidative stress affects the contractile behavior of smooth muscle resulting in complications during labor. Toxicants such as lindane and ferric chloride (FeCl3)/adenosine diphosphate (ADP) cause oxidative stress and have previously been shown to inhibit smooth muscle contraction. In this study we examined the effects of the oxygen species scavengers, ascorbic acid and N-acetylcysteine on lindane and FeCl3/ADP's inhibition of spontaneous myometrial contractions in rat and human myometrium. Lindane and FeCl3/ADP gave rise to concentration-dependent reductions in rat (EC50 11.8×10-6M and 0.9×10-3M) and human myometrial contractions (EC50 16.3×10-6M and 1.1×10-3M, respectively). Pre-treatment with N-acetylcysteine significantly increased the EC50 for the effects of lindane on motility index of human tissue and reduced the maximum inhibitory effect of FeCl3/ADP on contractions in both rat and human myometrium. Ascorbic acid reduced the effects of FeCl3/ADP in rat tissue only. In conclusion pre-treatment with specific antioxidants may protect both rat and human myometrium from the inhibitory effects of lindane and FeCl3/ADP.

Mot1, Ino80C, and NC2 Function Coordinately to Regulate Pervasive Transcription in Yeast and Mammals.

Pervasive transcription initiates from cryptic promoters and is observed in eukaryotes ranging from yeast to mammals. The Set2-Rpd3 regulatory system prevents cryptic promoter function within expressed genes. However, conserved systems that control pervasive transcription within intergenic regions have not been well established. Here we show that Mot1, Ino80 chromatin remodeling complex (Ino80C), and NC2 co-localize on chromatin and coordinately suppress pervasive transcription in S. cerevisiae and murine embryonic stem cells (mESCs). In yeast, all three proteins bind subtelomeric heterochromatin through a Sir3-stimulated mechanism and to euchromatin via a TBP-stimulated mechanism. In mESCs, the proteins bind to active and poised TBP-bound promoters along with promoters of polycomb-silenced genes apparently lacking TBP. Depletion of Mot1, Ino80C, or NC2 by anchor away in yeast or RNAi in mESCs leads to near-identical transcriptome phenotypes, with new subtelomeric transcription in yeast, and greatly increased pervasive transcription in both yeast and mESCs.

Using actor-partner interdependence modeling to understand HPV vaccine acceptance.

A wealth of scientific literature has been devoted to understanding what factors influence parents and their adolescent children to obtain the HPV vaccine. This literature is relatively uniform in its methodological approach of sampling individuals (i.e., either parents or adolescents) and examining the predictors of uptake for that individual. To improve understanding of HPV vaccination uptake, we sampled low-income, African American parent-child dyads with either a female (n = 93) or a male (n = 116) adolescent who had not been vaccinated. Both parents and children completed self-report measures that tapped intent to receive the vaccine and hypothesized predictors of intent (i.e., self-efficacy, beliefs about the vaccine, beliefs about HPV, knowledge of HPV). Using a dyadic analytic approach (i.e., the Actor-Partner Interdependence Model or APIM) [1], we found that parents and their adolescents have different structures of beliefs regarding HPV vaccination (i.e., they are empirically distinguishable). Consistent with prior research, the majority of predictors of an individual's own intention to vaccinate were individual-level variables; uniquely though, some predictors endorsed by one member of the dyad influenced the intentions held by the other member. Specifically, parents' reports of HPV severity and their self-efficacy were both associated with adolescents' intent to obtain the vaccine. Further, adolescents' beliefs that the vaccine will lead to greater promiscuity or be stigmatizing were associated with parents holding an increased intent to vaccinate. Use APIM improves understanding of HPV vaccination uptake and can be used to guide intervention efforts.

Endoplasmic reticulum-mitochondria junction is required for iron homeostasis.

The endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES) is a protein complex that physically tethers the two organelles to each other and creates the physical basis for communication between them. ERMES functions in lipid exchange between the ER and mitochondria, protein import into mitochondria, and maintenance of mitochondrial morphology and genome. Here, we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell. This function is independent of known ERMES roles in calcium regulation, phospholipid biosynthesis, or effects on mitochondrial morphology. A mutation in the vacuolar protein sorting 13 (VPS13) gene that rescues the glycolytic phenotype of ERMES mutants suppresses the iron deficiency response and iron accumulation. Our findings reveal that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels.

Gender Differences in Relations among Perceived Family Characteristics and Risky Health Behaviors in Urban Adolescents.

BACKGROUND: Research regarding the role of gender in relations between family characteristics and health risk behaviors has been limited. PURPOSE: This study aims to investigate gender differences in associations between family processes and risk-taking in adolescents. METHODS: Adolescents (N = 249; mean age = 14.5 years) starting their first year at an urban high school in the northeastern USA completed self-report measures that assessed family characteristics (i.e., parental monitoring, family social support, family conflict) and health behaviors (i.e., tobacco use, alcohol use, marijuana use, sex initiation) as part of a prospective, community-based study. Multivariate logistic regression models were used to investigate gender differences in associations between the family characteristics and health behaviors. RESULTS: Among males, higher levels of perceived parental monitoring were associated with lower odds of using tobacco and having ever engaged in sex. Among females, higher levels of perceived parental monitoring were associated with lower odds of marijuana use, alcohol use, and having ever engaged in sex. However, in contrast to males, among females (a) higher levels of perceived family social support were associated with lower odds of alcohol use and having ever engaged in sex and (b) higher levels of perceived family conflict were associated with higher odds of marijuana use and having ever engaged in sex. CONCLUSION: Family processes were more strongly related to health behaviors among adolescent females than adolescent males. Interventions that increase parental monitoring and family social support as well as decrease family conflict may help to protect against adolescent risk taking, especially for females.

EP400 Deposits H3.3 into Promoters and Enhancers during Gene Activation.

Gene activation in metazoans is accompanied by the presence of histone variants H2AZ and H3.3 within promoters and enhancers. It is not known, however, what protein deposits H3.3 into chromatin or whether variant chromatin plays a direct role in gene activation. Here we show that chromatin containing acetylated H2AZ and H3.3 stimulates transcription in vitro. Analysis of the Pol II pre-initiation complex on immobilized chromatin templates revealed that the E1A binding protein p400 (EP400) was bound preferentially to and required for transcription stimulation by acetylated double-variant chromatin. EP400 also stimulated H2AZ/H3.3 deposition into promoters and enhancers and influenced transcription in vivo at a step downstream of the Mediator complex. EP400 efficiently exchanged recombinant histones H2A and H3.1 with H2AZ and H3.3, respectively, in a chromatin- and ATP-stimulated manner in vitro. Our data reveal that EP400 deposits H3.3 into chromatin alongside H2AZ and contributes to gene regulation after PIC assembly.