Structural rearrangements maintain the Glycan Shield of an HIV-1 envelope trimer after the loss of a glycan

The HIV-1 envelope (Env) glycoprotein is the primary target of the humoral immune response and a critical vaccine candidate. However, Env is densely glycosylated and thereby substantially protected from neutralisation. Importantly, glycan N301 shields V3 loop and CD4 binding site epitopes from neutralising antibodies. Here, we use molecular dynamics techniques to evaluate the structural rearrangements that maintain the protective qualities of the glycan shield after the loss of glycan N301. We examined a naturally occurring subtype C isolate and its N301A mutant; the mutant not only remained protected against neutralising antibodies targeting underlying epitopes, but also exhibited an increased resistance to the VRC01 class of broadly neutralising antibodies. Analysis of this mutant revealed several glycans that were responsible, independently or through synergy, for the neutralisation resistance of the mutant. These data provide detailed insight into the glycan shield’s ability to compensate for the loss of a glycan, as well as the cascade of glycan movements on a protomer, starting at the point mutation, that affects the integrity of an antibody epitope located at the edge of the diminishing effect. These results present key, previously overlooked, considerations for HIV-1 Env glycan research and related vaccine studies.IS

The effect of railroads and price responsiveness on acreage decisions in the post-Bellum period

This study analyses the effect of farmers' price responsiveness and railroad development on acreage decisions in the late 19th century. A potential simultaneity between these determinants was mentioned in some earlier studies, but never examined. This study sheds some light on these relationships by employing a simultaneous equations model. The results show that acreage, prices and railroad mileage were jointly determined in the late nineteenth century. Furthermore, farmers were very responsive to wheat prices in their wheat acreage decisions in the eastern and northeastern regions when endogeneity effect is considered. In the western and southern regions, however, farmers were not responsive to wheat prices in their wheat acreage decisions. On the other hand, they were very responsive to corn and animal prices in their corn acreage decisions. Railroads were one important determinant that affected farmers' acreage decisions positively in every region.

Beyond the Five Senses: A Synaesthetic-Design Approach to Humanize Healthcare Environments

Several areas, such as evidence-based healthcare design, salutogenic architecture and environmental psychology, agree with the importance of the built environment (e.g., space, equipment and environmental variables) in the patients’ healing process. Poor quality sensorial stimuli appears to increase psychological distress and, indirectly, be linked to negative implications for patients’ and workers’ health and well-being. These factors have been also associated with poor judgment regarding hospitals’ overall quality, which continue to be perceived as inhuman and stressful places. A systematic literature review on the topic revealed either a gap regarding the consideration of human senses in the design process or a poor understanding of its complexity and richness. This article explores the sensory dimension of healthcare environments, from the synaesthetic design perspective. This approach considers the entire phenomenology of human perception; Specifically, we intend to discuss the potential of sensory interactions between sensations, found to affect the general condition of well-being, for the conceptualization and development of sensory based solutions for healthcare environments. Research issues and challenges in the design of healthcare environments will be highlighted