Transparent dense sodium

Under pressure, metals exhibit increasingly shorter interatomic distances. Intuitively, this response is expected to be accompanied by an increase in the widths of the valence and conduction bands and hence a more pronounced free-electron-like behaviour. But at the densities that can now be achieved experimentally, compression can be so substantial that core electrons overlap. This effect dramatically alters electronic properties from those typically associated with simple free-electron metals such as lithium and sodium, leading in turn to structurally complex phases and superconductivity with a high critical temperature. But the most intriguing prediction - that the seemingly simple metals Li and Na will transform under pressure into insulating states, owing to pairing of alkali atoms - has yet to be experimentally confirmed. Here we report experimental observations of a pressure-induced transformation of Na into an optically transparent phase at 200 GPa (corresponding to 5.0-fold compression). Experimental and computational data identify the new phase as a wide bandgap dielectric with a six-coordinated, highly distorted double-hexagonal close-packed structure. We attribute the emergence of this dense insulating state not to atom pairing, but to p-d hybridizations of valence electrons and their repulsion by core electrons into the lattice interstices. We expect that such insulating states may also form in other elements and compounds when compression is sufficiently strong that atomic cores start to overlap strongly.Comment: Published in Nature 458, 182-185 (2009

The role of resuscitation promoting factors in pathogenesis and reactivation of Mycobacterium tuberculosis during intra-peritoneal infection in mice

<p>Abstract</p> <p>Background</p> <p><it>Mycobacterium tuberculosis </it>can enter into a dormant state which has resulted in one third of the world's population being infected with latent tuberculosis making the study of latency and reactivation of utmost importance. <it>M. tuberculosis </it>encodes five resuscitation promoting factors (Rpfs) that bear strong similarity to a lysozyme-like enzyme previously implicated in reactivation of dormant bacteria <it>in vitro</it>.</p> <p>We have developed an intraperitoneal infection model in mice, with immune modulation, that models chronic infection with similar properties in mouse lungs as those observed in the murine aerosol infection model. We have assessed the behavior of mutants that lack two or three <it>rpf </it>genes in different combinations in our intraperitoneal model.</p> <p>Methods</p> <p>C57Bl/6 mice were intraperitonealy infected with H37Rv wild type <it>M. tuberculosis </it>or mutant strains that lacked two or three <it>rpf </it>genes in different combinations. After 90 days of infection aminoguanidine (AG) or anti-TNFα antibodies were administrated. Organ bacillary loads were determined at various intervals post infection by plating serial dilutions of organ homogenates and enumerating bacteria.</p> <p>Results</p> <p>We found that the <it>rpf </it>triple and double mutants tested were attenuated in their ability to disseminate to mouse lungs after intraperitoneal administration and were defective in their ability to re-grow after immunosuppression induced by administration of aminoguanidine and anti-TNFα antibodies.</p> <p>Conclusion</p> <p>Rpf proteins may have a significant physiological role for development of chronic TB infection and its reactivation <it>in vivo</it>.</p

Predicting the Impact of Climate Change on Threatened Species in UK Waters

Global climate change is affecting the distribution of marine species and is thought to represent a threat to biodiversity. Previous studies project expansion of species range for some species and local extinction elsewhere under climate change. Such range shifts raise concern for species whose long-term persistence is already threatened by other human disturbances such as fishing. However, few studies have attempted to assess the effects of future climate change on threatened vertebrate marine species using a multi-model approach. There has also been a recent surge of interest in climate change impacts on protected areas. This study applies three species distribution models and two sets of climate model projections to explore the potential impacts of climate change on marine species by 2050. A set of species in the North Sea, including seven threatened and ten major commercial species were used as a case study. Changes in habitat suitability in selected candidate protected areas around the UK under future climatic scenarios were assessed for these species. Moreover, change in the degree of overlap between commercial and threatened species ranges was calculated as a proxy of the potential threat posed by overfishing through bycatch. The ensemble projections suggest northward shifts in species at an average rate of 27 km per decade, resulting in small average changes in range overlap between threatened and commercially exploited species. Furthermore, the adverse consequences of climate change on the habitat suitability of protected areas were projected to be small. Although the models show large variation in the predicted consequences of climate change, the multi-model approach helps identify the potential risk of increased exposure to human stressors of critically endangered species such as common skate (Dipturus batis) and angelshark (Squatina squatina)

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

Estimating the Magnitude and Direction of Altered Arbovirus Transmission Due to Viral Phenotype

Vectorial capacity is a measure of the transmission potential of a vector borne pathogen within a susceptible population. Vector competence, a component of the vectorial capacity equation, is the ability of an arthropod to transmit an infectious agent following exposure to that agent. Comparisons of arbovirus strain-specific vector competence estimates have been used to support observed or hypothesized differences in transmission capability. Typically, such comparisons are made at a single time point during the extrinsic incubation period, the time in days it takes for the virus to replicate and disseminate to the salivary glands. However, vectorial capacity includes crucial parameters needed to effectively evaluate transmission capability, though often this is based on the discrete vector competence values. Utilization of the rate of change of vector competence over a range of days gives a more accurate measurement of the transmission potential. Accordingly, we investigated the rate of change in vector competence of dengue virus in Aedes aegypti mosquitoes and the resulting vectorial capacity curves. The areas under the curves represent the effective vector competence and the cumulative transmission potentials of arboviruses within a population of mosquitoes. We used the calculated area under the curve for each virus strain and the corresponding variance estimates to test for differences in cumulative transmission potentials between strains of dengue virus based on our dynamic model. To further characterize differences between dengue strains, we devised a displacement index interpreted as the capability of a newly introduced strain to displace the established, dominant circulating strain. The displacement index can be used to better understand the transmission dynamics in systems where multiple strains/serotypes circulate or even multiple arbovirus species. The use of a rate of a rate of change based model of vectorial capacity and the informative calculations of the displacement index will lead to better measurements of the differences in transmission potential of arboviruses

A Qualitative Assessment of Participation in a Rapid Scale-Up, Diagonally-Integrated MDG-Related Disease Prevention Campaign in Rural Kenya

Background: Many countries face severe scale-up barriers toward achievement of MDGs. We ascertained motivational and experiential dimensions of participation in a novel, rapid, ‘‘diagonal’ ’ Integrated Prevention Campaign (IPC) in rural Kenya that provided prevention goods and services to 47,000 people within one week, aimed at rapidly moving the region toward MDG achievement. Specifically, the IPC provided interventions and commodities targeting disease burden reduction in HIV/ AIDS, malaria, and water-borne illness. Methods: Qualitative in-depth interviews (IDI) were conducted with 34 people (18 living with HIV/AIDS and 16 not HIVinfected) randomly selected from IPC attendees consenting to participate. Interviews were examined for themes and patterns to elucidate participant experience and motivation with IPC. Findings: Participants report being primarily motivated to attend IPC to learn of their HIV status (through voluntary counseling and testing), and with receipt of prevention commodities (bednets, water filters, and condoms) providing further incentive. Participants reported that they were satisfied with the IPC experience and offered suggestions to improve future campaigns. Interpretation: Learning their HIV status motivated participants along with the incentive of a wider set of commodities that were rapidly deployed through IPC in this challenging region. The critical role of wanting to know their HIV status combine

CD8+ DC, but Not CD8−DC, Isolated from BCG-Infected Mice Reduces Pathological Reactions Induced by Mycobacterial Challenge Infection

Tuberculosis is a mycobacterial infection causing worldwide public health problems but the available vaccine is far from ideal. Type-1 T cell immunity has been shown to be critical for host defence against tuberculosis infection, but the role of dendritic cell (DC) subsets in pathogenesis of mycobacterial infection remains unclear.We examined the effectiveness of dendritic cell (DC) subsets in BCG-infected mice in generating immune responses beneficial for pathogen clearance and reduction of pathological reactions in the tissues following challenge infection. Our data showed that only the adoptive transfer of the subset of CD8alpha+ DC isolated from infected mice (iCD8+ DC) generated significant protection, demonstrated by less mycobacterial growth and pathological changes in the lung and liver tissues in iCD8+ DC recipients than sham-treated control mice. The adoptive transfer of the CD8alpha(-)DC from the infected mice (iCD8(-) DC) not only failed to reduce bacterial growth, but enhanced inflammation characterized by diffuse heavy cellular infiltration. Notably, iCD8(-) DC produced significantly higher levels of IL-10 than iCD8+ DC and promoted more Th2 cytokine responses in in vitro DC-T cell co-culture and in vivo adoptive transfer experiments.The data indicate that in vivo BCG-primed CD8+ DC is the dominant DC subset in inducing protective immunity especially for reducing pathological reactions in infected tissues. The finding has implications for the rational improvement of the prophylactic and therapeutic approaches for controlling tuberculosis infection and related diseases

An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis

Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (M. tuberculosis), is a major cause of morbidity and mortality worldwide and efforts to control TB are hampered by difficulties with diagnosis, prevention and treatment 1,2. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease, but current tests cannot identify which individuals will develop disease 3. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines 4,5. We identified a whole blood 393 transcript signature for active TB in intermediate and high burden settings, correlating with radiological extent of disease and reverting to that of healthy controls following treatment. A subset of latent TB patients had signatures similar to those in active TB patients. We also identified a specific 86-transcript signature that discriminated active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-γ and Type I IFNαβ signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis, suggest that this TB signature reflects both changes in cellular composition and altered gene expression. Although an IFN signature was also observed in whole blood of patients with Systemic Lupus Erythematosus (SLE), their complete modular signature differed from TB with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto under-appreciated role of Type I IFNαβ signalling in TB pathogenesis, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic