The Falls In Care Home study: a feasibility randomized controlled trial of the use of a risk assessment and decision support tool to prevent falls in care homes.

Objective: To explore the feasibility of implementing and evaluating the Guide to Action Care Home fall prevention intervention.

Design: Two-centre, cluster feasibility randomized controlled trial and process evaluation.

Setting: Purposive sample of six diverse old age/learning disability, long stay care homes in Nottinghamshire, UK.

Modern applications for a total sulfur reduction distillation method - what's old is new again.

Background: The use of a boiling mixture of hydriodic acid, hypophosphorous acid, and hydrochloric acid to reduce any variety of sulfur compounds has been in use in various applications since the first appearance of this method in the literature in the 1920's. In the realm of sulfur geochemistry, this method remains a useful, but under-utilized technique. Presented here is a detailed description of the distillation set-up and procedure, as well as an overview of potential applications of this method for marine sulfur biogeochemistry/isotope studies.

Correction: Chimeric Rhinoviruses Displaying MPER Epitopes Elicit Anti-HIV Neutralizing Responses.

[This corrects the article on p. e72205 in vol. 8.

Chimeric rhinoviruses displaying MPER epitopes elicit anti-HIV neutralizing responses.

Background: The development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER) of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV.

Methodology/principle Findings: Guided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV) displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic surface loop of HRV via linkers of varying lengths and sequences.

The reversibility of dissimilatory sulphate reduction and the cell-internal multi-step reduction of sulphite to sulphide: insights from the oxygen isotope composition of sulphate.

Dissimilatory sulphate reduction (DSR) leads to an overprint of the oxygen isotope composition of sulphate by the oxygen isotope composition of water. This overprint is assumed to occur via cell-internally formed sulphuroxy intermediates in the sulphate reduction pathway. Unlike sulphate, the sulphuroxy intermediates can readily exchange oxygen isotopes with water.

Antigenic characteristics of rhinovirus chimeras designed in silico for enhanced presentation of HIV-1 gp41 epitopes [corrected].

The development of an effective AIDS vaccine remains the most promising long-term strategy to combat human immunodeficiency virus (HIV)/AIDS. Here, we report favorable antigenic characteristics of vaccine candidates isolated from a combinatorial library of human rhinoviruses displaying the ELDKWA epitope of the gp41 glycoprotein of HIV-1. The design principles of this library emerged from the application of molecular modeling calculations in conjunction with our knowledge of previously obtained ELDKWA-displaying chimeras, including knowledge of a chimera with one of the best 2F5-binding characteristics obtained to date.

Broad neutralization of human immunodeficiency virus type 1 (HIV-1) elicited from human rhinoviruses that display the HIV-1 gp41 ELDKWA epitope.

In efforts to develop AIDS vaccine components, we generated combinatorial libraries of recombinant human rhinoviruses that display the well-conserved ELDKWA epitope of the membrane-proximal external region of human immunodeficiency virus type 1 (HIV-1) gp41. The broadly neutralizing human monoclonal antibody 2F5 was used to select for viruses whose ELDKWA conformations resemble those of HIV. Immunization of guinea pigs with different chimeras, some boosted with ELDKWA-based peptides, elicited antibodies capable of neutralizing HIV-1 pseudoviruses of diverse subtypes and coreceptor usages.

Isotopic evidence for an aerobic nitrogen cycle in the latest Archean.

The nitrogen cycle provides essential nutrients to the biosphere, but its antiquity in modern form is unclear. In a drill core though homogeneous organic-rich shale in the 2.5-billion-year-old Mount McRae Shale, Australia, nitrogen isotope values vary from +1.

In silico vaccine design based on molecular simulations of rhinovirus chimeras presenting HIV-1 gp41 epitopes.

A cluster of promising epitopes for the development of human immunodeficiency virus (HIV) vaccines is located in the membrane-proximal external region (MPER) of the gp41 subunit of the HIV envelope spike structure. The crystal structure of the peptide corresponding to the so-called ELDKWA epitope (HIV-1 HxB2 gp41 residues 662-668), in complex with the corresponding broadly neutralizing human monoclonal antibody 2F5, provides a target for structure-based vaccine design strategies aimed at finding macromolecular carriers that are able to present this MPER-derived epitope with optimal antigenic activity. To this end, a series of replica exchange molecular dynamics computer simulations was conducted to characterize the distributions of conformations of ELDKWA-based epitopes inserted into a rhinovirus carrier and to identify those with the highest fraction of conformations that are able to bind 2F5.

A whiff of oxygen before the great oxidation event?

High-resolution chemostratigraphy reveals an episode of enrichment of the redox-sensitive transition metals molybdenum and rhenium in the late Archean Mount McRae Shale in Western Australia. Correlations with organic carbon indicate that these metals were derived from contemporaneous seawater. Rhenium/osmium geochronology demonstrates that the enrichment is a primary sedimentary feature dating to 2501 +/- 8 million years ago (Ma).

Late Archean biospheric oxygenation and atmospheric evolution.

High-resolution geochemical analyses of organic-rich shale and carbonate through the 2500 million-year-old Mount McRae Shale in the Hamersley Basin of northwestern Australia record changes in both the oxidation state of the surface ocean and the atmospheric composition. The Mount McRae record of sulfur isotopes captures the widespread and possibly permanent activation of the oxidative sulfur cycle for perhaps the first time in Earth's history. The correlation of the time-series sulfur isotope signals in northwestern Australia with equivalent strata from South Africa suggests that changes in the exogenic sulfur cycle recorded in marine sediments were global in scope and were linked to atmospheric evolution.

Structural and molecular interactions of CCR5 inhibitors with CCR5.

We have characterized the structural and molecular interactions of CC-chemokine receptor 5 (CCR5) with three CCR5 inhibitors active against R5 human immunodeficiency virus type 1 (HIV-1) including the potent in vitro and in vivo CCR5 inhibitor aplaviroc (AVC). The data obtained with saturation binding assays and structural analyses delineated the key interactions responsible for the binding of CCR5 inhibitors with CCR5 and illustrated that their binding site is located in a predominantly lipophilic pocket in the interface of extracellular loops and within the upper transmembrane (TM) domain of CCR5. Mutations in the CCR5 binding sites of AVC decreased gp120 binding to CCR5 and the susceptibility to HIV-1 infection, although mutations in TM4 and TM5 that also decreased gp120 binding and HIV-1 infectivity had less effects on the binding of CC-chemokines, suggesting that CCR5 inhibition targeting appropriate regions might render the inhibition highly HIV-1-specific while preserving the CC chemokine-CCR5 interactions.

Crystal structure of a human rhinovirus that displays part of the HIV-1 V3 loop and induces neutralizing antibodies against HIV-1.

We report the 2.7 A resolution structure of a chimeric rhinovirus, MN-III-2, that displays part of the HIV-1 gp120 V3 loop and elicits HIV-neutralizing antibodies. The V3 loop insert is dominated by two type I beta turns.