Correlated Depletion and Dilution of Lithium and Beryllium Revealed by Subgiants in M 67

The surface content of lithium (Li) and beryllium (Be) provide insights into the mixing and circulation mechanisms in stellar interiors. The old open cluster, M 67, has been well-studied for Li abundances in both main-sequence and evolved stars. The Be abundances give us a probe to a deeper level in stars. We have taken high-resolution spectra with Keck I with HIRES to determine Be abundances along the subgiant branch of M 67, where there are dramatic depletions of Li. These subgiants range in mass from 1.26 to 1.32 M$_{\odot}$ and have evolved from main-sequence stars that would have occupied the region of the Li-Be dip found in younger clusters. Lithium abundances have been adjusted to the same scale for 103 stars in M 67 by Pace et al. The more massive stars $-$ now the coolest and furthest-evolved from the main-sequence $-$ show a drop in Li by a factor of 400 across the subgiant branch. Our new Be abundances also show a decline, but by a factor of $\sim$50. The two elements decline together with Li showing a steeper decline in these subgiants than it does in the Li-Be dip stars. The relative decline in Be abundance compared to Li is remarkably well fit by the models of Sills & Deliyannis, made specifically for the subgiants in M 67. Those models include the effects of mixing induced by stellar rotation. These M 67 subgiants show the effects of both main-sequence depletion and post-main-sequence dilution of both Li and Be.Comment: 31 pages with 3 tables, 13 figures Accepted by Ap. J. 10/7/201

Lithium and Beryllium in One Solar Mass Stars

The surface content of lithium (Li) and beryllium (Be) in stars can reveal important information about the temperature structure and physical processes in their interior regions. This study focuses on solar-type stars with a sample that is more precisely defined than done previously. Our selection of stars studied for Be is constrained by five parameters: mass, temperature, surface gravity, metallicity, and age to be similar to the Sun and is focussed on stars within +-0.02 of 1 M_sun. We have used the Keck I telescope with HIRES to obtain spectra of the Be II spectral region of 52 such stars at high spectral resolution ($\sim$45,000) and high signal-to-noise ratios. While the spread in Li in these stars is greater than a factor of 400, the spread in Be is only 2.7 times. Two stars were without any Be, perhaps due to a merger or a mass transfer with a companion. We find a steep trend of Li with temperature but little for Be. While there is a downward trend in Li with [Fe/H] from -0.4 to +0.4 due to stellar depletion, there is a small increase in Be with Fe from Galactic Be enrichment. While there is a broad decline in Li with age, there may be a small increase in Be with age, though age is less well-determined. In the subset of stars closest to the Sun in temperature and other parameters we find that the ratio of the abundances of Be to Li is much lower than predicted by models; there may be other mixing mechanisms causing additional Li depletion.Comment: total 29 pages including 12 figures, 5 tables Accepted for Astrophysical Journa

Does Manual Therapy Provide Additional Benefit To Breathing Retraining In The Management Of Dysfunctional Breathing? A Randomised Controlled Trial

Purpose: Dysfunctional breathing (DB) is associated with an abnormal breathing pattern, unexplained breathlessness and significant patient morbidity. Treatment involves breathing retraining through respiratory physiotherapy. Recently, manual therapy (MT) has also been used, but no evidence exists to validate its use. This study sought to investigate whether MT produces additional benefit when compared with breathing retraining alone in patients with DB. Methods: Sixty subjects with primary DB were randomised into either breathing retraining (standard treatment; n¼30) or breathing retraining plus MT (intervention; n¼30) group. Both the groups received standardised respiratory physiotherapy, which included: DB education, breathing retraining, home regimen, and audio disc. Intervention group subjects additionally received MT following further assessment. Data from 57 subjects were analysed. Results: At baseline, standard treatment group subjects were statistically younger (41.7 + 13.5 versus 50.8 + 13.0 years; p¼0.001) with higher Nijmegen scores (38.6 + 9.5 versus 31.5 + 6.9; p¼0.001). However, no significant difference was found between the groups for primary outcome Nijmegen score (95% CI ( 1.1, 6.6) p¼0.162), or any secondary outcomes (Hospital Anxiety & Depression Score, spirometry or exercise tolerance). Conclusion: Breathing retraining is currently the mainstay of treatment for patients with DB. The results of this study suggest MT provides no additional benefit in this patient group.Juliana Burgess, Dr Robert Wilson, Royal Brompton & Harefield NHS Foundation Trust, and Dr Andy Jones fo

Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress

SummaryWe screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. Passive transfer of broadly neutralizing MAbs protected mice against infection by chikungunya, Mayaro, and O’nyong’nyong alphaviruses. Using alanine-scanning mutagenesis, loss-of-function recombinant proteins and viruses, and multiple functional assays, we determined that broadly neutralizing MAbs block multiple steps in the viral lifecycle, including entry and egress, and bind to a conserved epitope on the B domain of the E2 glycoprotein. A 16 Å resolution cryo-electron microscopy structure of a Fab fragment bound to CHIKV E2 B domain provided an explanation for its neutralizing activity. Binding to the B domain was associated with repositioning of the A domain of E2 that enabled cross-linking of neighboring spikes. Our results suggest that B domain antigenic determinants could be targeted for vaccine or antibody therapeutic development against multiple alphaviruses of global concern

A mammalian functional-genetic approach to characterizing cancer therapeutics

Supplementary information is available online at http://www.nature.com/naturechemicalbiology/. Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/.Identifying mechanisms of drug action remains a fundamental impediment to the development and effective use of chemotherapeutics. Here we describe an RNA interference (RNAi)–based strategy to characterize small-molecule function in mammalian cells. By examining the response of cells expressing short hairpin RNAs (shRNAs) to a diverse selection of chemotherapeutics, we could generate a functional shRNA signature that was able to accurately group drugs into established biochemical modes of action. This, in turn, provided a diversely sampled reference set for high-resolution prediction of mechanisms of action for poorly characterized small molecules. We could further reduce the predictive shRNA target set to as few as eight genes and, by using a newly derived probability-based nearest-neighbors approach, could extend the predictive power of this shRNA set to characterize additional drug categories. Thus, a focused shRNA phenotypic signature can provide a highly sensitive and tractable approach for characterizing new anticancer drugs.National Institute of Mental Health (U.S.) (grant RO1 CA128803-03)American Association for Cancer ResearchMassachusetts Institute of Technology. Dept. of BiologyNational Cancer Institute (U.S.). Integrative Cancer Biology Program (grant 1-U54-CA112967

Ancient Microbes from Halite Fluid Inclusions: Optimized Surface Sterilization and DNA Extraction

Fluid inclusions in evaporite minerals (halite, gypsum, etc.) potentially preserve genetic records of microbial diversity and changing environmental conditions of Earth's hydrosphere for nearly one billion years. Here we describe a robust protocol for surface sterilization and retrieval of DNA from fluid inclusions in halite that, unlike previously published methods, guarantees removal of potentially contaminating surface-bound DNA. The protocol involves microscopic visualization of cell structures, deliberate surface contamination followed by surface sterilization with acid and bleach washes, and DNA extraction using Amicon centrifugal filters. Methods were verified on halite crystals of four different ages from Saline Valley, California (modern, 36 ka, 64 ka, and 150 ka), with retrieval of algal and archaeal DNA, and characterization of the algal community using ITS1 sequences. The protocol we developed opens up new avenues for study of ancient microbial ecosystems in fluid inclusions, understanding microbial evolution across geological time, and investigating the antiquity of life on earth and other parts of the solar system