Structural and functional insights into DNA-end processing by the archaeal HerA helicase-NurA nuclease complex

Helicase-nuclease systems dedicated to DNA end resection in preparation for homologous recombination (HR) are present in all kingdoms of life. In thermophilic archaea, the HerA helicase and NurA nuclease cooperate with the highly conserved Mre11 and Rad50 proteins during HR-dependent DNA repair. Here we show that HerA and NurA must interact in a complex with specific subunit stoichiometry to process DNA ends efficiently. We determine crystallographically that NurA folds in a toroidal dimer of intertwined RNaseH-like domains. The central channel of the NurA dimer is too narrow for double-stranded DNA but appears well suited to accommodate one or two strands of an unwound duplex. We map a critical interface of the complex to an exposed hydrophobic epitope of NurA abutting the active site. Based upon the presented evidence, we propose alternative mechanisms of DNA end processing by the HerA-NurA complex.Research in the N.P.R. laboratory is funded by the Medical Research Council [Career Development Award (G0701443)]. Research in L.P. laboratory is funded by a Wellcome Trust Senior Fellowship Award in Basic Biomedical Sciences (08279/Z/07/Z). Funding for open access charge: the Medical Research (G0701443 to N.P.R.) and the Wellcome Trust (08279/Z/07/Z to L.P.) and the Department of Biochemistry, University of Cambridge

Solving Quantum Ground-State Problems with Nuclear Magnetic Resonance

Quantum ground-state problems are computationally hard problems; for general many-body Hamiltonians, there is no classical or quantum algorithm known to be able to solve them efficiently. Nevertheless, if a trial wavefunction approximating the ground state is available, as often happens for many problems in physics and chemistry, a quantum computer could employ this trial wavefunction to project the ground state by means of the phase estimation algorithm (PEA). We performed an experimental realization of this idea by implementing a variational-wavefunction approach to solve the ground-state problem of the Heisenberg spin model with an NMR quantum simulator. Our iterative phase estimation procedure yields a high accuracy for the eigenenergies (to the 10^-5 decimal digit). The ground-state fidelity was distilled to be more than 80%, and the singlet-to-triplet switching near the critical field is reliably captured. This result shows that quantum simulators can better leverage classical trial wavefunctions than classical computers.Comment: 11 pages, 13 figure

Primary gastric tuberculosis – report of 5 cases

BACKGROUND: Gastric tuberculosis is rare, and usually associated with pulmonary tuberculosis or an immunodeficient state. Here, we report five cases of gastric tuberculosis in immunocompetent patients without evidence of pulmonary involvement. CASE PRESENTATION: Three patients presented with gastric outlet obstruction that required surgery to relieve the obstruction as well as to confirm the diagnosis. The remaining two had involvement of gastroesophageal junction. All of them responded well to standard antitubercular treatment. CONCLUSION: Though gastric tuberculosis is rare, it should be considered a possibility when patients present with gastric outlet obstruction or with endoscopic evidence of diffuse chronic inflammatory activity, particularly in areas endemic for tuberculosis

Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

A neonate with left pulmonary artery thrombosis and left lung hypoplasia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spontaneous intrauterine arterial thrombosis and congenital pulmonary hypoplasia are rare conditions and have not been reported to occur together. The literature rather includes two reports of babies with neonatal pulmonary artery occlusion and post-infarction cysts of the lungs.</p> <p>Case presentation</p> <p>We report a case of a live Caucasian male newborn with left lung hypoplasia that occurred in association with left pulmonary artery thrombosis. Despite a critical neonatal course, including extracorporeal membrane oxygenation, this infant is alive and well at 18 months of age without any neurodevelopmental sequelae or reactive airway disease.</p> <p>Conclusion</p> <p>This association suggests the possibility of an intrauterine vascular event between the fifth and eighth weeks of gestation during early pulmonary artery and lung development.</p

Let’s celebrate recovery. Inclusive Cities working together to support social cohesion

Recovery from illicit drug and alcohol use takes place over time and is characterised by a dynamic interaction between internal and external components. An integral part of all recovery journeys is effective community reintegration. After all, recovery is not mainly an issue of personal motivation rather it is about acceptance by family, by friends and by a range of organisations and professionals across the community. Therefore to support pathways to recovery, structural and contextual endeavours are needed to supplement individually-oriented interventions and programmes. One way to do this, is by introducing Inclusive Cities. An Inclusive City promotes participation, inclusion, full and equal citizenship to all her citizens, including those in recovery, based on the idea of community capital. The aim of building recovery capital at a community level through connections and 'linking social capital' to challenge stigmatisation and exclusion, is seen as central to this idea. Inclusive Cities is an initiative to support the creation of Recovery-Oriented Systems of Care at a city level, that starts with but extends beyond substance using populations. This paper describes (and gives examples of) how it is possible to use recovery as a starting point for generating social inclusion, challenging the marginalisation of other excluded populations as well by building community connections

Iron Incorporation and Post-Malaria Anaemia

BACKGROUND: Iron supplementation is employed to treat post-malarial anaemia in environments where iron deficiency is common. Malaria induces an intense inflammatory reaction that stalls reticulo-endothelial macrophagal iron recycling from haemolysed red blood cells and inhibits oral iron absorption, but the magnitude and duration of these effects are unclear. METHODOLOGY/PRINCIPAL FINDINGS: We examined the red blood cell incorporation of oral administered stable isotopes of iron and compared incorporation between age matched 18 to 36 months old children with either anaemia post-malaria (n = 37) or presumed iron deficiency anaemia alone (n = 36). All children were supplemented for 30 days with 2 mg/kg elemental iron as liquid iron sulphate and administered (57)Fe and (58)Fe on days 1 and 15 of supplementation respectively. (57)Fe and(58)Fe incorporation were significantly reduced (8% vs. 28%: p<0.001 and 14% vs. 26%: p = 0.045) in the malaria vs. non-malaria groups. There was a significantly greater haemoglobin response in the malaria group at both day 15 (p = 0.001) and 30 (p<0.000) with a regression analysis estimated greater change in haemoglobin of 7.2 g/l (s.e. 2.0) and 10.1 g/l (s.e. 2.5) respectively. CONCLUSION/SIGNIFICANCE: Post-malaria anaemia is associated with a better haemoglobin recovery despite a significant depressant effect on oral iron incorporation which may indicate that early erythropoetic iron need is met by iron recycling rather than oral iron. Supplemental iron administration is of questionable utility within 2 weeks of clinical malaria in children with mild or moderate anaemia

Interoperable atlases of the human brain

International audienceThe last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different as-pects of the human brain including micro-and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topo-graphically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and represen-tation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored

What are the evolutionary constraints on larval growth in a trophically transmitted parasite?

For organisms with a complex life cycle, a large larval size is generally beneficial, but it may come at the expense of prolonged development. Individuals that grow fast may avoid this tradeoff and switch habitats at both a larger size and younger age. A fast growth rate itself can be costly, however, as it requires greater resource intake. For parasites, fast larval growth is assumed to increase the likelihood of host death before transmission to the next host occurs. Using the tapeworm Schistocephalus solidus in its copepod first intermediate host, I investigated potential constraints in the parasite’s larval life history. Fast-growing parasites developed infectivity earlier, indicating there is no functional tradeoff between size and developmental time. There was significant growth variation among full-sib worm families, but fast-growing sibships were not characterized by lower host survival or more predation-risky host behavior. Parental investment also had little effect on larval growth rates. The commonly assumed constraints on larval growth and development were not observed in this system, so it remains unclear what prevents worms from exploiting their intermediate hosts more aggressively

Rare Bilateral Nasopalatine Duct Cysts: A Case Report

The nasopalatine duct cyst (NPDC) is the most common of the non-odontogenic cyst of the jaws. This cysts are usually central or unilateral with no prevalence of side occurrence. The NPDC is the most frequent developmental, nonodontogenic cyst of the jaws. This cyst originates from epithelial remnants from the nasopalatine duct. The cells could be activated spontaneously during life, or are eventually stimulated by the irritating action of various agents (infection, etc.). Generally, patients present without clinical signs and symptoms. Therefore, the tentative diagnosis "nasopalatine duct cyst" is often based on a coincidental radiological finding on a routine panoramic view or occlusal radiograph. The definite diagnosis should be based on clinical, radiological and above all histopathologic findings. The therapy of nasopalatine duct cysts consists of an enucleation of the cystic tissue, only in rare cases a marsupialization needs to be performed. This report describes the appearance and treatment of a rare case of bilateral nasopalatine duct cyst