Overcoming Ethical Challenges to Engaging Men Who Have Sex with Women in HIV Research.

Men who have sex with women are understudied in HIV research despite the extent to which they experience HIV-related mortality and contribute to the epidemic among women. During our experience of developing and piloting an HIV prevention intervention for men living with HIV in South Africa, and planning to have a child with an HIV-negative woman, ethical questions were posed regarding implementation of a male-centered intervention that did not require female partner participation. Two overarching ethical issues were the potential for (1) compromising women's reproductive and sexual autonomy and (2) increasing HIV-acquisition risks for the woman because the intervention efficacy was unknown. We describe here how these concerns were addressed to facilitate development of a male-centered HIV-prevention intervention. We hope this process manuscript will support researchers, clinicians, and reviewers to engage men who have sex with women in HIV prevention and care.

Beating the one-half limit of ancilla-free linear optics Bell measurements.

We show that optically encoded two-qubit Bell states can be unambiguously discriminated with a success probability of more than 50% in both single-rail and dual-rail encodings by using active linear-optical resources that include Gaussian squeezing operations. These results are in contrast to the well-known upper bound of 50% for unambiguous discrimination of dual-rail Bell states using passive, static linear optics and arbitrarily many vacuum modes. We present experimentally feasible schemes that improve the success probability to 64.3% in dual-rail and to 62.5% in single-rail for a uniform random distribution of Bell states. Conceptually, this demonstrates that neither interactions that induce nonlinear mode transformations (such as Kerr interactions) nor auxiliary entangled photons are required to go beyond the one-half limit. We discuss the optimality of our single-rail scheme and talk about an application of our dual-rail scheme in quantum communication.

The Effects of Framework Mutations at the Variable Domain Interface on Antibody Affinity Maturation in an HIV-1 Broadly Neutralizing Antibody Lineage.

Understanding affinity maturation of antibodies that can target many variants of HIV-1 is important for vaccine development. While the antigen-binding site of antibodies is known to mutate throughout the co-evolution of antibodies and viruses in infected individuals, the roles of the mutations in the antibody framework region are not well understood. Throughout affinity maturation, the CH103 broadly neutralizing antibody lineage, from an individual designated CH505, altered the orientation of one of its antibody variable domains. The change in orientation was a response to insertions in the variable loop 5 (V5) of the HIV envelope. In this study, we generated CH103 lineage antibody variants in which residues in the variable domain interface were mutated, and measured the binding to both autologous and heterologous HIV-1 envelopes. Our data show that very few mutations in an early intermediate antibody of the lineage can improve binding toward both autologous and heterologous HIV-1 envelopes. We also crystallized an antibody mutant to show that framework mutations alone can result in a shift in relative orientations of the variable domains. Taken together, our results demonstrate the functional importance of residues located outside the antigen-binding site in affinity maturation.

Corrigendum: The Effects of Framework Mutations at the Variable Domain Interface on Antibody Affinity Maturation in an HIV-1 Broadly Neutralizing Antibody Lineage.

[This corrects the article DOI: 10.3389/fimmu.2020.01529.].

RNA synthesis is associated with multiple TBP-chromatin binding events.

Competition ChIP is an experimental method that allows transcription factor (TF) chromatin turnover dynamics to be measured across a genome. We develop and apply a physical model of TF-chromatin competitive binding using chemical reaction rate theory and are able to derive the physical half-life or residence time for TATA-binding protein (TBP) across the yeast genome from competition ChIP data. Using our physical modeling approach where we explicitly include the induction profile of the competitor in the model, we are able to estimate yeast TBP-chromatin residence times as short as 1.3 minutes, demonstrating that competition ChIP is a relatively high temporal-resolution approach. Strikingly, we find a median value of ~5 TBP-chromatin binding events associated with the synthesis of one RNA molecule across Pol II genes, suggesting multiple rounds of pre-initiation complex assembly and disassembly before productive elongation of Pol II is achieved at most genes in the yeast genome.