A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.

Approximately a quarter of the human genome consists of gene deserts, large regions devoid of genes often located adjacent to developmental genes and thought to contribute to their regulation. However, defining the regulatory functions embedded within these deserts is challenging due to their large size. Here, we explore the cis-regulatory architecture of a gene desert flanking the Shox2 gene, which encodes a transcription factor indispensable for proximal limb, craniofacial, and cardiac pacemaker development.

Provider Factors Likely to Impact Access and Uptake of Long-Acting Injectable Cabotegravir for Transgender Women in the United States: Results of a Qualitative Study.

Long-acting injectable cabotegravir (CAB-LA) was US Food and Drug Administration-approved in 2021. However, little is known about providers' CAB-LA knowledge, attitudes, challenges, and prescribing preferences for transgender women patients. Understanding this is critical to developing new pre-exposure prophylaxis (PrEP) interventions tailored to transgender women.

Improving Recruitment and Retention of Transgender Women in HIV Prevention Trials: Strategies to Make Trial Participation More Congruent with the Needs of Transgender Women.

Transgender women are disproportionately burdened by HIV. Though there is a substantial body of research exploring barriers and facilitators of HIV prevention among transgender women, many barriers remain unaddressed. This study identifies strategies to make HIV prevention trials more congruent with transgender women's preferences and needs to boost trial participation and ultimately enhance initiation and uptake of pre-exposure prophylaxis (PrEP).

Navigating Barriers and Opportunities: Perceptions of the Non-Occupational Post-Exposure Prophylaxis Care Continuum Among Young Sexual Minority Men, Aged 17-24, in the United States.

Human immunodeficiency virus (HIV) is a public health concern among young sexual minority men (YSMM), ages 17 to 24, in the United States. Biomedical prevention methods, such as pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP), can help reduce the risk of HIV transmission among this population. However, there is limited awareness and use of nPEP by YSMM.

Conserved -Acting Range Extender Element Mediates Extreme Long-Range Enhancer Activity in Mammals.

While most mammalian enhancers regulate their cognate promoters over moderate distances of tens of kilobases (kb), some enhancers act over distances in the megabase range. The sequence features enabling such extreme-distance enhancer-promoter interactions remain elusive. Here, we used enhancer replacement experiments in mice to show that short- and medium-range enhancers cannot initiate gene expression at extreme-distance range.

Increased enhancer-promoter interactions during developmental enhancer activation in mammals.

Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here we investigate the three-dimensional (3D) conformation of enhancers during mammalian development by generating high-resolution tissue-resolved contact maps for nearly a thousand enhancers with characterized in vivo activities in ten murine embryonic tissues. Sixty-one percent of developmental enhancers bypass their neighboring genes, which are often marked by promoter CpG methylation.

Pathogenic Aβ production by heterozygous PSEN1 mutations is intrinsic to the mutant protein and not mediated by conformational hindrance of wild-type PSEN1.

Presenilin-1 (PSEN1) is the catalytic subunit of the intramembrane protease γ-secretase and undergoes endoproteolysis during its maturation. Heterozygous mutations in the PSEN1 gene cause early-onset familial Alzheimer's disease (eFAD) and increase the proportion of longer aggregation-prone amyloid-β peptides (Aβ42 and/or Aβ43). Previous studies had suggested that PSEN1 mutants might act in a dominant-negative fashion by functional impediment of wild-type PSEN1, but the exact mechanism by which PSEN1 mutants promote pathogenic Aβ production remains controversial.

Transgender Women's Experiences Using SMARTtest, a Smartphone Application to Facilitate Self- and Partner-HIV/Syphilis Testing Using the INSTI Multiplex.

We present experiences of transgender women (TW) who have sex with men with SMARTtest, a smartphone app to accompany the INSTI Multiplex, a one-minute, dual blood-based HIV/syphilis rapid test. TW participants (N = 11) received 10 INSTI Multiplex tests to take home for self- and/or partner-testing and installed the SMARTtest app on their phones. The SMARTtest app aimed to support INSTI Multiplex users in correctly performing the test, interpreting the results, and connecting with care following a positive HIV or syphilis screening.

Topologically associating domain boundaries are required for normal genome function.

Topologically associating domain (TAD) boundaries partition the genome into distinct regulatory territories. Anecdotal evidence suggests that their disruption may interfere with normal gene expression and cause disease phenotypes, but the overall extent to which this occurs remains unknown. Here we demonstrate that targeted deletions of TAD boundaries cause a range of disruptions to normal in vivo genome function and organismal development.

Rapid or Immediate ART, HIV Stigma, Medical Mistrust, and Retention in Care: An Exploratory Mixed Methods Pilot Study.

Rapid or immediate antiretroviral therapy (iART) after HIV diagnosis improves linkage to care and time to viral suppression. However, iART may affect or be affected by HIV-related stigma and medical mistrust. In this mixed-methods pilot study, we examined the bi-directional role of HIV stigma, medical mistrust, and visit adherence (VA) in the context of iART in a diverse, newly diagnosed patient population.

Engagement in Care Among Newly Diagnosed HIV-Positive Gay, Bisexual, and Other Men Who Have Sex With Men in the United States: Results From the Together 5,000 Study.

One-quarter of gay, bisexual, and other men who have sex with men (GBMSM) with diagnosed HIV are not engaged in HIV care. Between 2018 and 2019, 50 GBMSM completed qualitative interviews 3 months after receiving an HIV-positive result. Interviews explored barriers to and facilitators of engagement and retention in HIV testing and care.

Negotiating Use of a Blood-Based, Dual HIV and Syphilis Test with Potential Sexual Partners Among a Sample of Cisgender Men and Transgender Women Who Have Sex with Men in New York City.

Cisgender men who have sex with men (cMSM) and transgender women (TGW) are disproportionally burdened by HIV. Among these populations, HIV partner-testing is a highly acceptable harm reduction tool. Particularly, cMSM and TGW report a stronger preference for blood-based tests that include assays for multiple STIs.

The / gene regulatory network precedes the origin of paired fins and reveals the deep homology between distal fins and digits.

One of the central problems of vertebrate evolution is understanding the relationship among the distal portions of fins and limbs. Lacking comparable morphological markers of these regions in fish and tetrapods, these relationships have remained uncertain for the past century and a half. Here we show that Gli3 functions in controlling the proliferative expansion of distal progenitors are shared among dorsal and paired fins as well as tetrapod limbs.

Experiences of Transgender Women Who Used a Dual HIV/Syphilis Rapid Self-test to Screen Themselves and Potential Sexual Partners (the SMARTtest Study).

HIV/syphilis self- and partner-testing may be especially appropriate for transgender women, since they shoulder a disproportionate burden of HIV, other STIs (e.g., syphilis), and report high levels of medical mistrust.

Spatial regulation by multiple Gremlin1 enhancers provides digit development with cis-regulatory robustness and evolutionary plasticity.

Precise cis-regulatory control of gene expression is essential for normal embryogenesis and tissue development. The BMP antagonist Gremlin1 (Grem1) is a key node in the signalling system that coordinately controls limb bud development. Here, we use mouse reverse genetics to identify the enhancers in the Grem1 genomic landscape and the underlying cis-regulatory logics that orchestrate the spatio-temporal Grem1 expression dynamics during limb bud development.

Transgender Women's Barriers, Facilitators, and Preferences on Tailored Injection Delivery Strategies to Administer Long-Acting Injectable Cabotegravir (CAB-LA) for HIV Pre-exposure Prophylaxis (PrEP).

Long-acting injectable cabotegravir (CAB-LA) is in advanced stages of clinical trials. Under the standard protocol, CAB-LA is injected into the gluteal muscle by a healthcare provider every eight weeks. To explore transgender women's barriers and facilitators to tailored delivery strategies-including self-injection and injection in "drop-in" centers-we completed in-depth interviews with N = 15 transgender women in New York City.

Acceptability and Use of a Dual HIV/Syphilis Rapid Test and Accompanying Smartphone App to Facilitate Self- and Partner-Testing Among Cisgender Men and Transgender Women Who Have Sex with Men.

At home self- and partner-testing may reduce HIV and syphilis transmission by detecting undiagnosed infections. Forty-eight cisgender men and transgender women who men who have sex with men were given ten INSTI Multiplex kits and downloaded the SMARTtest app to facilitate self- and partner testing over the next three months. Thirty-seven (77%) participants self-tested using the INSTI (mean = 3.

Attitudes and Perceptions About Disclosing HIV and Syphilis Results Using Smarttest, a Smartphone App Dedicated to Self- and Partner Testing.

We explored interest in disclosing test results through a smartphone app dedicated to self- and partner testing for HIV/syphilis. Fifty-nine cisgender men and transgender women each participated in an in-person survey and interview. We examined their interests in sharing test results by audience (e.

Experiences Receiving HIV-Positive Results by Phone: Acceptability and Implications for Clinical and Behavioral Research.

Improving HIV testing rates and increasing early detection among men who have sex with men (MSM) are critical strategies for enhancing overall health and decreasing HIV transmission. Remote testing and phone delivery of HIV test results may reduce barriers such as geographic isolation or HIV-related stigma. In 2018-19, 50 MSM completed qualitative interviews about their experience receiving a positive HIV test result via phone through their participation in a research study that included remote HIV testing.

Willingness to Distribute HIV Self-Testing Kits to Recent Sex Partners Among HIV-Negative Gay and Bisexual Men and an Examination of Free-Response Data from Young Men Participating in the Nationwide Cohort.

Sexual minority men (SMM)-and young SMM in particular-are disproportionately affected by HIV. Secondary distribution of HIV self-testing (HIVST) kits-wherein patients deliver kits to partners-is a novel strategy to increase HIV testing access. Using quantitative data, we assessed willingness to distribute HIVST kits to recent sex partners among a U.

Using an HIV Self-test Kit to Test a Partner: Attitudes and Preferences Among High-Risk Populations.

For those most at risk of contracting HIV, new strategies for preventing transmission and increasing testing are needed. As part of a multi-site, randomized, controlled trial, we explored attitudes and preferences among 272 HIV-negative men who have sex with men and HIV-negative transgender women using an HIV self-testing (HIVST) kit to test partners. Less than one quarter had previously self-tested with HIVST kits (21.