Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.
Background: Healthcare systems globally are expanding community pharmacy services to meet patient needs and reduce healthcare costs. In England this includes helping community pharmacies to provide integrated professional services but concerns persist over quality of care. This study aimed to identify priorities from key stakeholders for improving the quality of professional community pharmacy services.
Background: The post-ICU home recovery period requires patients and caregivers to confront recovery challenges and adopt coping strategies as a family dyad, necessitating effective dyadic interaction patterns. Existing qualitative research shows that the dyads face interactive or independent challenges and employs varying coping strategies, which may include strong communication or, conversely, avoidance. However, a single qualitative study alone might offer limited generalizability, and there is a lack of broader, more nuanced understanding about the recovery challenge and copings among ICU survivors and caregivers.
Research on virus/receptor interactions has uncovered various mechanisms of antibody-mediated neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, understanding of neutralization by antibodies targeting the silent face, which recognize epitopes on glycan shields, remains limited, and their potential protective efficacy in vivo is not well understood. This study describes a silent face neutralizing antibody, 3711, which targets a non-supersite on the N-terminal domain (NTD) of the spike protein.
Aeronautical structures can be damaged by objects during operation and maintenance. Indeed, foreign object impacts (FOIs) affect the overall performance of composite structural components. Delamination is the most critical damage mechanism as it is undetectable and develops silently.
Mobile ICT, such as smartphones and tablets, has become integral for everyday tasks like finance, communication, and entertainment. While these technologies offer significant opportunities for integration and combating loneliness, visually impaired individuals still face challenges. These include practical barriers due to poor universal design, motivational hurdles, and inadequate lifelong education.
