Designing a sustainable strategy for malaria control?

Malaria in the 21st century is showing signs of declining over much of its distribution, including several countries in Africa where previously this was not thought to be feasible. Yet for the most part the strategies to attack the infection are similar to those of the 1950s. Three major Journals have recently drawn attention to the situation, stressing the importance of research, describing the successes and defining semantics related to control. But there is a need to stress the importance of local sustainability, and consider somewhat urgently how individual endemic countries can plan and implement the programmes that are currently financed, for the most part, by donor institutions. On an immediate basis research should be more focused on a data driven approach to control. This will entail new thinking on the role of local infrastructure and in training of local scientists in local universities in epidemiology and field malariology so that expanded control programmes can become operational. Donor agencies should encourage and facilitate development of career opportunities for such personnel so that local expertise is available to contribute appropriately

Extremely metal-poor gas at a redshift of 7

In typical astrophysical environments, the abundance of heavy elements ranges from 0.001 to 2 times the solar value. Lower abundances have been seen in selected stars in the Milky Way’s halo and in two quasar absorption systems at redshift z = 3 (ref. 4). These are widely interpreted as relics from the early Universe, when all gas possessed a primordial chemistry. Before now there have been no direct abundance measurements from the first billion years after the Big Bang, when the earliest stars began synthesizing elements. Here we report observations of hydrogen and heavy-element absorption in a spectrum of a quasar at z =  7.04, when the Universe was just 772 million years old (5.6 per cent of its present age). We detect a large column of neutral hydrogen but no corresponding metals (defined as elements heavier than helium), limiting the chemical abundance to less than 1/10,000 times the solar level if the gas is in a gravitationally bound proto-galaxy, or to less than 1/1,000 times the solar value if it is diffuse and unbound. If the absorption is truly intergalactic, it would imply that the Universe was neither ionized by starlight nor chemically enriched in this neighbourhood at z ≈ 7. If it is gravitationally bound, the inferred abundance is too low to promote efficient cooling, and the system would be a viable site to form the predicted but as yet unobserved massive population III stars

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Whole Genome Sequencing and Complete Genetic Analysis Reveals Novel Pathways to Glycopeptide Resistance in Staphylococcus aureus

The precise mechanisms leading to the emergence of low-level glycopeptide resistance in Staphylococcus aureus are poorly understood. In this study, we used whole genome deep sequencing to detect differences between two isogenic strains: a parental strain and a stable derivative selected stepwise for survival on 4 µg/ml teicoplanin, but which grows at higher drug concentrations (MIC 8 µg/ml). We uncovered only three single nucleotide changes in the selected strain. Nonsense mutations occurred in stp1, encoding a serine/threonine phosphatase, and in yjbH, encoding a post-transcriptional negative regulator of the redox/thiol stress sensor and global transcriptional regulator, Spx. A missense mutation (G45R) occurred in the histidine kinase sensor of cell wall stress, VraS. Using genetic methods, all single, pairwise combinations, and a fully reconstructed triple mutant were evaluated for their contribution to low-level glycopeptide resistance. We found a synergistic cooperation between dual phospho-signalling systems and a subtle contribution from YjbH, suggesting the activation of oxidative stress defences via Spx. To our knowledge, this is the first genetic demonstration of multiple sensor and stress pathways contributing simultaneously to glycopeptide resistance development. The multifactorial nature of glycopeptide resistance in this strain suggests a complex reprogramming of cell physiology to survive in the face of drug challenge

450 d of Type II SN 2013ej in optical and near-infrared

We present optical and near-infrared photometric and spectroscopic observations of SN 2013ej, in galaxy M74, from 1 to 450 d after the explosion. SN 2013ej is a hydrogen-rich supernova, classified as a Type IIL due to its relatively fast decline following the initial peak. It has a relatively high peak luminosity (absolute magnitude M$_V$ = −17.6) but a small $^{56}$Ni production of ~0.023 M$_{\odot}$. Its photospheric evolution is similar to other Type II SNe, with shallow absorption in the H$_α$ profile typical for a Type IIL. During transition to the radioactive decay tail at ~100 d, we find the SN to grow bluer in $\textit{B − V}$ colour, in contrast to some other Type II supernovae. At late times, the bolometric light curve declined faster than expected from $^{56}$Co decay and we observed unusually broad and asymmetric nebular emission lines. Based on comparison of nebular emission lines most sensitive to the progenitor core mass, we find our observations are best matched to synthesized spectral models with a $\textit{M}$$_{ZAMS}$ = 12–15 M$_{\odot}$ progenitor. The derived mass range is similar to but not higher than the mass estimated for Type IIP progenitors. This is against the idea that Type IIL are from more massive stars. Observations are consistent with the SN having a progenitor with a relatively low-mass envelope.The authors would like to thank Melissa Graham for scheduling the LCOGT observations. This paper is based on observations collected at the European Organization for Astronomical Research in the Southern hemisphere, Chile as part of PESSTO, (the Public ESO Spectroscopic Survey for Transient Objects Survey) ESO programme ID 188.D-3003. The paper is partially based on observations collected at Copernico and Schmidt telescopes (Asiago, Italy) of the INAF – Osservatorio Astronomico di Padova. Some observations have been obtained also with the 1.22 m telescope + B&C spectrograph operated in Asiago by the Department of Physics and Astronomy of the University of Padova. This paper is partly based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), Ministerio de Ciencia, Tecnologıa e Innovacion Productiva (Argentina), and Ministerio da Ciencia, Tecnologia e Inovacao (Brazil). This research was made possible through the use of the APASS, funded by the Robert Martin Ayers Sciences Fund. This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. Parts of this research were conducted by the Australian Research Council Centre of Excellence for All-sky Astrophysics (CAASTRO), through project number CE110001020. IRS was supported by the ARC Laureate Grant FL0992131. SB, AP, NER and GT are partially supported by the PRIN-INAF 2014 project ‘Transient Universe: unveiling new types of stellar explosions with PESSTO’. SSchulze acknowledges support from CONICYT-Chile FONDECYT 3140534, Basal-CATA PFB-06/2007, and Project IC120009 ‘Millennium Institute of Astrophysics (MAS)’ of Initiative Cientıfica Milenio del Ministerio de Economıa, Fomento y Turismo. This work was partly supported by the European Union FP7 programme through ERC grant number 320360. KM acknowledges support from the STFC through an Ernest Rutherford Fellowship. MS acknowledges support from STFC grant ST/L000679/1 and EU/FP7- ERC grant no. [615929]. AGY is supported by the EU/FP7 via ERC grant no. 307260, the Quantum Universe I- CORE Program by the Israeli Committee for Planning and Budgeting and the Israel Science Foundation (ISF); by Minerva and ISF grants; by the Weizmann-UK making connections programme; and by Kimmel and ARCHES awards.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw141

Observational and Physical Classification of Supernovae

This chapter describes the current classification scheme of supernovae (SNe). This scheme has evolved over many decades and now includes numerous SN Types and sub-types. Many of these are universally recognized, while there are controversies regarding the definitions, membership and even the names of some sub-classes; we will try to review here the commonly-used nomenclature, noting the main variants when possible. SN Types are defined according to observational properties; mostly visible-light spectra near maximum light, as well as according to their photometric properties. However, a long-term goal of SN classification is to associate observationally-defined classes with specific physical explosive phenomena. We show here that this aspiration is now finally coming to fruition, and we establish the SN classification scheme upon direct observational evidence connecting SN groups with specific progenitor stars. Observationally, the broad class of Type II SNe contains objects showing strong spectroscopic signatures of hydrogen, while objects lacking such signatures are of Type I, which is further divided to numerous subclasses. Recently a class of super-luminous SNe (SLSNe, typically 10 times more luminous than standard events) has been identified, and it is discussed. We end this chapter by briefly describing a proposed alternative classification scheme that is inspired by the stellar classification system. This system presents our emerging physical understanding of SN explosions, while clearly separating robust observational properties from physical inferences that can be debated. This new system is quantitative, and naturally deals with events distributed along a continuum, rather than being strictly divided into discrete classes. Thus, it may be more suitable to the coming era where SN numbers will quickly expand from a few thousands to millions of events.Comment: Extended final draft of a chapter in the "SN Handbook". Comments most welcom

Autistic Disorder in Patients with Williams-Beuren Syndrome: A Reconsideration of the Williams-Beuren Syndrome Phenotype

International audienceBackground: Williams-Beuren syndrome (WBS), a rare developmental disorder caused by deletion of contiguous genes at 7q11.23, has been characterized by strengths in socialization (overfriendliness) and communication (excessive talkativeness). WBS has been often considered as the polar opposite behavioral phenotype to autism. Our objective was to better understand the range of phenotypic expression in WBS and the relationship between WBS and autistic disorder. Methodology: The study was conducted on 9 French individuals aged from 4 to 37 years old with autistic disorder associated with WBS. Behavioral assessments were performed using Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) scales. Molecular characterization of the WBS critical region was performed by FISH. Findings: FISH analysis indicated that all 9 patients displayed the common WBS deletion. All 9 patients met ADI-R and ADOS diagnostic criteria for autism, displaying stereotypies and severe impairments in social interaction and communication (including the absence of expressive language). Additionally, patients showed improvement in social communication over time. Conclusions: The results indicate that comorbid autism and WBS is more frequent than expected and suggest that the common WBS deletion can result in a continuum of social communication impairment, ranging from excessive talkativeness and overfriendliness to absence of verbal language and poor social relationships. Appreciation of the possible co-occurrence of WBS and autism challenges the common view that WBS represents the opposite behavioral phenotype of autism, and might lead to improved recognition of WBS in individuals diagnosed with autism

Epigenetic regulation of centromeric chromatin: old dogs, new tricks?

The assembly of just a single kinetochore at the centromere of each sister chromatid is essential for accurate chromosome segregation during cell division. Surprisingly, despite their vital function, centromeres show considerable plasticity with respect to their chromosomal locations and activity. The establishment and maintenance of centromeric chromatin, and therefore the location of kinetochores, is epigenetically regulated. The histone H3 variant CENP-A is the key determinant of centromere identity and kinetochore assembly. Recent studies have identified many factors that affect CENP-A localization, but their precise roles in this process are unknown. We build on these advances and on new information about the timing of CENP-A assembly during the cell cycle to propose new models for how centromeric chromatin is established and propagated