Decoding protein dynamicity in DNA ligase activity through deep learning-based structural ensembles.

Numerous proteins perform their functions by transitioning between various structures. Understanding the conformational ensembles associated with these states is essential for uncovering crucial mechanistic aspects that regulate protein function. In this study, we utilized AlphaFold3 () to investigate the structural dynamics and mechanisms of enzymes involved in DNA homeostasis, using NAD-dependent Taq ligases and human DNA Ligase 1 as a case example.

Focused learning by antibody language models using preferential masking of non-templated regions.

Existing antibody language models () are pre-trained using a masked language modeling () objective with uniform masking probabilities. While these models excel at predicting germline residues, they often struggle with mutated and non-templated residues, which are crucial for antigen-binding specificity and concentrate in the complementarity-determining regions (). Here, we demonstrate that preferential masking of the non-templated CDR3 is a compute-efficient strategy to enhance model performance.

A Qualitative Assessment of South Africa's Central Chronic Medication Dispensing and Distribution Program for Differentiated Antiretroviral Therapy Delivery in Umlazi Township, South Africa: Client Perspectives after 12 Months of Participation.

South Africa's Central Chronic Medicine Dispensing and Distribution (CCMDD) program provides community-based medication delivery for clinically stable people with HIV (PWH) on antiretroviral therapy (ART). To evaluate CCMDD implementation, we conducted semi-structured interviews with 60 PWH enrolled in CCMDD for at least 12 months. In a directed content analysis based on the Practical, Robust Implementation and Sustainability Model (PRISM) implementation science framework, key themes were compared with qualitative data collected from PWH enrolling in CCMDD at an earlier time-point.

Examining naloxone access and interest in secondary naloxone distribution on an American Indian Reservation in the Northern Midwest of the United States.

Background: Indigenous communities in the United States experience disproportionate rates of overdose morbidity and mortality due to a range of historical traumas and ongoing oppression. Limited health and harm reduction service access on some Tribal lands exacerbate these challenges. To date, little is known about naloxone access on tribal reservation lands.

Advances in HIV management and challenges in Japan: Current situation of pre-exposure prophylaxis in Tokyo.

Since the world's first case series of human immunodeficiency virus (HIV) infection were reported, more than 40 decades have passed. The advancement of HIV treatment and prevention has progressed drastically. Especially, the efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention has been proven by a number of trials and the number of new HIV cases has declined over the years due to the large-scale and rapid implementation of PrEP and universal HIV treatment in multiple countries.

Early inflammation as a footprint of increased mortality risk in infants living with HIV from three African countries.

In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation.

Decreased variability in the site-specific results during participation in the External Quality Assurance Program Oversight Laboratory (EQAPOL) proficiency program for IFN-gamma enzyme-linked immunospot (IFN-γ ELISpot) assay.

The NIAID DAIDS-sponsored External Quality Assurance Program Oversight Laboratory (EQAPOL) manages an interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) external proficiency program. The ELISpot program evaluates the accuracy and variability of results across laboratories. The variability in the program is quantified via the dispersion, which is the ratio of the variance over the mean of the background-corrected spot-forming cells (SFC) replicates obtained under stimulation with different peptide pools (CMV, CEF).

2'3'-cGAMP interactome identifies 2'3'-cGAMP/Rab18/FosB signaling in cell migration control independent of innate immunity.

c-di-GAMP was first identified in bacteria to promote colonization, while mammalian 2'3'-cGAMP is synthesized by cGAS to activate STING for innate immune stimulation. However, 2'3'-cGAMP function beyond innate immunity remains elusive. Here, we report that 2'3'-cGAMP promotes cell migration independent of innate immunity.

Factors associated with medications for opioid use disorder (MOUD) treatment success during the pregnancy and postpartum periods: A scoping review.

Background: Medications for opioid use disorder (MOUD) are a crucial intervention for pregnant and postpartum individuals with opioid use disorder (OUD). However, there is paucity of data on the factors associated with MOUD treatment success in this population. This scoping review aimed to evaluate factors associated with MOUD success during the pregnancy and postpartum period.

Advancing Human Vaccine Development Using Humanized Mouse Models.

The development of effective vaccines against infectious diseases remains a critical challenge in global health. Animal models play a crucial role in vaccine development by providing valuable insights into the efficacy, safety, and mechanisms of immune response induction, which guide the design and formulation of vaccines. However, traditional animal models often inadequately recapitulate human immune responses.

CD57+ T Cell Transmigration Through Vascular Endothelial Cells is Enhanced by Tumor Necrosis Factor: A Novel Model of Cardiovascular Risk in People with HIV.

People with human immunodeficiency virus (PWH), despite achieving viral suppression through antiretroviral therapy, face increased risk and earlier onset of atherosclerotic cardiovascular diseases than the general population. CD57+ T cells can be readily recovered from atherosclerotic plaques and likely contribute to disease by targeting endothelial cells (ECs); however, the specific mechanisms facilitating the infiltration of these cells into plaques remain elusive. Here, we report the development of a novel assay to quantify T cell adhesion to and transmigration through a primary human vascular EC monolayer and show that CD57+ T cells preferentially adhere to and transmigrate through the monolayer.

AI-based IsAb2.0 for antibody design.

Therapeutic antibody design has garnered widespread attention, highlighting its interdisciplinary importance. Advancements in technology emphasize the critical role of designing nanobodies and humanized antibodies in antibody engineering. However, current experimental methods are costly and time-consuming.

Provider Perspectives on Rapid Treatment Initiation Among People Newly Diagnosed With HIV: A New Message of "Urgency"?

Background: Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program.

Methods: We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020).

Lessons Learned from a Community-led, Pilot Teletherapy Group for Older Women Living with Depression and HIV.

Older women with HIV face challenges to their quality of life, including neurocognitive decline, early-onset menopause, and chronic health issues. Chief among these concerns is depression, the most common psychiatric comorbidity among people living with HIV, with rates twice as high among women as men. However, tailored interventions among older women living with HIV and depression are lacking.

Immunization with germ line-targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques.

Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for implementing an immunization regimen. Because the elicitation of broadly neutralizing antibodies (bnAbs) is critical for an effective HIV vaccine, our goal was to assess the ability of a bnAb B cell lineage-designed HIV envelope SOSIP (protein stabilized by a disulfide bond between gp120-gp41-named "SOS"-and an isoleucine-to-proline point mutation-named "IP"-at residue 559) to induce precursor CD4 binding site (CD4bs)-targeting bnAbs in early life.