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Mutations in CDCA7, the SNF2 family protein HELLS (LSH), or the DNA methyltransferase DNMT3b cause immunodeficiency–centromeric instability–facial anomalies (ICF) syndrome. While it has been speculated that DNA methylation defects cause this disease, little is known about the molecular function of CDCA7 and its functional relationship to HELLS and DNMT3b. Systematic analysis of how the cell cycle, H3K9 methylation, and the mitotic kinase Aurora B affect proteomic profiles of chromatin in Xenopus egg extracts revealed that HELLS and CDCA7 form a stoichiometric complex on chromatin, in a manner sensitive to Aurora B. Although HELLS alone fails to remodel nucleosomes, we demonstrate that the HELLS–CDCA7 complex possesses nucleosome remodeling activity. Furthermore, CDCA7 is essential for loading HELLS onto chromatin, and CDCA7 harboring patient ICF mutations fails to recruit the complex to chromatin. Together, our study identifies a unique bipartite nucleosome remodeling complex where the functional remodeling activity is split between two proteins and thus delineates the defective pathway in ICF syndrome.

A new system to monitor the effects of nucleosome depletion in Xenopus egg extracts reveals that nucleosomes are required for spindle assembly and for recruitment of nuclear pore complex (NPC) components to the nuclear envelope for NPC formation. Nucleosomes are the fundamental unit of chromatin, but analysis of transcription-independent nucleosome functions has been complicated by the gene-expression changes resulting from histone manipulation. Here we solve this dilemma by developing Xenopus laevis egg extracts deficient for nucleosome formation and by analyzing the proteomic landscape and behavior of nucleosomal chromatin and nucleosome-free DNA. We show that although nucleosome-free DNA can recruit nuclear-envelope membranes, nucleosomes are required for spindle assembly and for formation of the lamina and of nuclear pore complexes (NPCs). We show that, in addition to the Ran G-nucleotide exchange factor RCC1, ELYS, the initiator of NPC formation, fails to associate with naked DNA but directly binds histone H2A–H2B dimers and nucleosomes. Tethering ELYS and RCC1 to DNA bypasses the requirement for nucleosomes in NPC formation in a synergistic manner. Thus, the minimal essential function of nucleosomes in NPC formation is to recruit RCC1 and ELYS.

Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, characterized by hypomethylation at heterochromatin. The unique zinc-finger domain, zf-4CXXC_R1, of CDCA7 is widely conserved across eukaryotes but is absent from species that lack HELLS and DNA methyltransferases, implying its specialized relation with methylated DNA. Here we demonstrate that zf-4CXXC_R1 acts as a hemimethylated DNA sensor. The zf-4CXXC_R1 domain of CDCA7 selectively binds to DNA with a hemimethylated CpG, but not unmethylated or fully methylated CpG, and ICF disease mutations eliminated this binding. CDCA7 and HELLS interact via their N-terminal alpha helices, through which HELLS is recruited to hemimethylated DNA. While placement of a hemimethylated CpG within the nucleosome core particle can hinder its recognition by CDCA7, cryo-EM structure analysis of the CDCA7-nucleosome complex suggests that zf-4CXXC_R1 recognizes a hemimethylated CpG in the major groove at linker DNA. Our study provides insights into how the CDCA7-HELLS nucleosome remodeling complex uniquely assists maintenance DNA methylation.

Pre-exposure prophylaxis (PrEP) is highly efficacious for preventing HIV but has not yet been brought to scale among at-risk persons. In several clinical trials in urban areas, technology-based interventions have shown a positive impact on PrEP adherence. In rural and small-town areas in the United States, which often do not have geographically proximal access to PrEP providers, additional support may be needed. This may be particularly true for younger persons who are more likely to face multiple barriers to accessing PrEP services. Home-based care, accomplished through a tailored mobile phone app, specimen self-collection (SSC), and interactive video consultations, could increase both PrEP initiation and persistence in care. The goal of this study is to assess the initiation and persistence in PrEP care for those randomized to a home-care intervention (electronic PrEP, ePrEP) relative to those assigned to the standard of care (control) condition. We will conduct additional assessments, including quantitative and qualitative analyses, to contextualize trial results and facilitate scale-up. This 2-arm, randomized controlled trial will enroll young men who have sex with men (YMSM) aged between 18 and 24 years from rural areas of Georgia, Mississippi, and North Carolina. The trial will seek to recruit a diverse sample, targeting 50% participation among highly impacted groups of black or Latino men who have sex with men. Intervention participants will receive a study app that incorporates a messaging platform, a scheduling and milestone-based tracking system for PrEP care progress, electronic behavioral surveys, and interactive video consultations with a clinician. Complemented by SSC kits mailed to laboratories for standard PrEP-related monitoring, the ePrEP system will allow participants to access PrEP care without leaving their homes. YMSM randomized to the control condition will receive a listing of nearest local PrEP providers to receive standard PrEP care. Both groups will complete quarterly electronic surveys. The primary outcome, assessed at 6 and 12 months after randomization, will be the difference in the proportion of intervention versus control participants that achieve protective levels of the active metabolite of oral PrEP (tenofovir diphosphate in dried blood spots). Enrollment will begin in May 2019, with study completion in 2022. This trial will determine whether home PrEP care provided through an app-based platform is an efficacious means of expanding access to PrEP care for a diverse group of YMSM in rural and small-town areas of the United States. ClinicalTrials.gov NCT03729570; https://clinicaltrials.gov/ct2/show/NCT03729570 (Archived by WebCite at http://www.webcitation.org/78RE2Qizf). PRR1-10.2196/13982.

Objectives. We examined the association between unprotected anal intercourse and sexually transmitted diseases (STDs) among heterosexual women. Methods. In 2006 through 2007, women were recruited from high-risk areas in New York City through respondent-driven sampling as part of the National HIV Behavioral Surveillance study. We used multiple logistic regression to determine the relationship between unprotected anal intercourse and HIV infection and past-year STD diagnosis. Results. Of the 436 women studied, 38% had unprotected anal intercourse in the past year. Unprotected anal intercourse was more likely among those who were aged 30 to 39 years, were homeless, were frequent drug or binge alcohol users, had an incarcerated sexual partner, had sexual partners with whom they exchanged sex for money or drugs, or had more than 5 sexual partners in the past year. In the logistic regression, women who had unprotected anal intercourse were 2.6 times as likely as women who had only unprotected vaginal intercourse and 4.2 times as likely as women who had neither unprotected anal nor unprotected vaginal intercourse to report an STD diagnosis. We found no significant association between unprotected anal intercourse and HIV infection. Conclusions. Increased screening for history of unprotected anal intercourse and, for those who report recent unprotected anal intercourse, counseling and testing for HIV and STDs would likely reduce STD infections.

Heterosexual partnerships involving the trade of money or goods for sex are a well-described HIV risk factor in Africa and Southeast Asia, but less research has been conducted on exchange partnerships and their impact on HIV infection in the United States. In our study, men and women were recruited from high-risk risk neighborhoods in New York City through respondent-driven sampling in 2006–2007. We examined the factors associated with having an exchange partner in the past year, the relationship between exchange partnerships and HIV infection, and the risk characteristics of those with exchange partners by the directionality of payment. Overall, 28% of men and 41% of women had a past-year exchange partner. For men, factors independently associated with exchange partnerships were older age, more total sexual partners, male partners, and frequent non-injection drug use. For women, factors were homelessness, more total sexual partners, more unprotected sex partners, and frequent non-injection drug use. Exchange partnerships were associated with HIV infection for both men and women, although the relationships were substantially confounded by other behavioral risks. Those who both bought and sold sex exhibited the highest levels of risk with their exchange and non-exchange partners. Exchange partnerships may be an HIV risk both directly and indirectly, given the overlap of this phenomenon with other risk factors that occur with both exchange and non-exchange partners.

We present Rubin Data Preview 1 (DP1), the first data from the National Science Foundation–Department of Energy Vera C. Rubin Observatory, comprising raw and calibrated single-epoch images, coadds, difference images, detection catalogs, and ancillary data products. DP1 is based on 1792 optical–near-infrared exposures acquired over 48 distinct nights by the Rubin Commissioning Camera (LSSTComCam) on the Simonyi Survey Telescope at the Summit Facility on Cerro Pachón, Chile in late 2024. DP1 covers ∼15 deg2 distributed across seven roughly equal-sized noncontiguous fields, each independently observed in six broad photometric bands, ugrizy. The median FWHM of the point-spread function across all bands is approximately 1 .″ 14, with the sharpest images reaching about 0 .″ 58. The 5σ point-source depths for coadded images in the deepest field, the Extended Chandra Deep Field South, are u = 24.55, g = 26.18, r = 25.96, i = 25.71, z = 25.07, and y = 23.1. Other fields are no more than 2.2 mag shallower in any band, where they have nonzero coverage. DP1 contains approximately 2.3 million distinct astrophysical objects, of which 1.6 million are extended in at least one band in coadds, and 431 solar system objects, of which 93 are new discoveries. DP1 is approximately 3.5 TB in size and is available to Vera C. Rubin Observatory data rights holders via the Rubin Science Platform, a cloud-based environment for the analysis of petascale astronomical data. While small compared to future LSST releases, its high quality and diversity of data support a broad range of early science investigations ahead of full operations in 2026.

We present SLIDE, a pipeline that enables transient discovery in data from the Vera C. Rubin Observatory’s Legacy Survey of Space and Time (LSST), using archival images from the Dark Energy Camera as templates for difference imaging. We apply this pipeline to the recently released Data Preview 1 (DP1; the first public release of Rubin commissioning data) and search for transients in the resulting difference images. The image subtraction, photometry extraction, and transient detection are all performed on the Rubin Science Platform. We demonstrate that SLIDE effectively extracts clean photometry by circumventing poor or missing LSST templates. We identified 29 previously unreported transients, 12 of which would not have been detected based on the DP1 DiaObject catalog. SLIDE will be especially useful for transient analysis in the early years of LSST, when template coverage will be largely incomplete or when templates may be contaminated by transients present at the time of acquisition. We present multiband light curves for a sample of known transients, along with new transient candidates identified through our search. Finally, we discuss the prospects of applying this pipeline during the main LSST survey. Our pipeline is broadly applicable and will support studies of all transients with slowly evolving phases.

Objectives. We investigated the impact of recruitment bias within the venuebased sampling (VBS) method, which is widely used to estimate disease prevalence and risk factors among groups, such as men who have sex with men (MSM), that congregate at social venues. Methods. In a 2008 VBS study of 479 MSM in New York City, we calculated venue-specific approach rates (MSM approached/MSM counted) and response rates (MSM interviewed/MSM approached), and then compared crude estimates of HIV risk factors and seroprevalence with estimates weighted to address the lower selection probabilities of MSM who attend social venues infrequently or were recruited at high-volume venues. Results. Our approach rates were lowest at dance clubs, gay pride events, and public sex strolls, where venue volumes were highest; response rates ranged from 39% at gay pride events to 95% at community-based organizations. Sixty-seven percent of respondents attended MSM-oriented social venues at least weekly, and 21% attended such events once a month or less often in the past year. In estimates adjusted for these variations, the prevalence of several past-year risk factors (e.g., unprotected anal intercourse with casual/exchange partners, >5 total partners, group sex encounters, at least weekly binge drinking, and hard-drug use) was significantly lower compared with crude estimates. Adjusted HIV prevalence was lower than unadjusted prevalence (15% vs. 18%), but not significantly. Conclusions. Not adjusting VBS data for recruitment biases could overestimate HIV risk and prevalence when the selection probability is greater for higher-risk MSM. While further examination of recruitment-adjustment methods for VBS data is needed, presentation of both unadjusted and adjusted estimates is currently indicated.

We report on the observation and measurement of astrometry, photometry, morphology, and activity of the interstellar object 3I/ATLAS, also designated C/2025 N1 (ATLAS) with the NSF-DOE Vera C. Rubin Observatory. Comet 3I/ATLAS, the third known interstellar object, was discovered on UT 2025 July 1. Rubin Observatory had coincidentally collected images of the object’s region of the sky during routine commissioning. Facilitated by Rubin’s high resolution and large aperture, we successfully recovered object detections from Rubin observations spanning UT 2025 June 21 (10 days before discovery, when 3I/ATLAS was 4.5 au from the Sun) through the date of discovery, and we acquired additional images through UT 2025 July 20 as part of commissioning. We measure on-sky locations of 3I/ATLAS in Rubin ugrizy bands, with a typical precision of ∼70 mas, and briefly describe the reason this is coarser than our measured static source astrometric precision of ∼3 mas in Rubin images. We measure grizy magnitudes of 3I/ATLAS photometry at ∼0.01 mag precision, detecting no short-term photometric variability above 0.01 mag. We derive an estimated near-nucleus dust-to-nucleus scattering cross-sectional ratio of η ≳ 13 on UT 2025 July 2 based on Rubin photometry and an upper limit nucleus size computed from Hubble Space Telescope observations. We find Rubin colors of g − r = (0.657 ± 0.013) mag, r − i = (0.235 ± 0.018) mag, i − z = (0.147 ± 0.042) mag, and z − y = (0.047 ± 0.052) mag. These data represent the earliest observations of this object by a large (≳8 m class) telescope and illustrate the type of measurements (and discoveries) Rubin’s Legacy Survey of Space and Time will provide after it begins in early 2026.