251 research outputs found

    Is Mindfulness for Psychosis harmful? Deconstructing a myth

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    Lipid Metabolism in Female Ascaris Lumbricoides During Starvation

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    Physiolog

    Methanol immersion reduces spherical aberration of water dipping lenses at long wavelengths used in multi-photon laser scanning microscopy

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    Dipping objectives were tested for multi-photon laser scanning microscopy, since their large working distances are advantageous for thick specimens and the absence of a coverslip facilitates examination of living material. Images of fluorescent bead specimens, particularly at wavelengths greater than 850 nm showed defects consistent with spherical aberration. Substituting methanol for water as the immersion medium surrounding the beads corrected these defects and produced an increase in fluorescence signal intensity. The same immersion method was applied to two representative biological samples of fixed tissue: mouse brain labeled with FITC for tubulin and mouse gut in which the Peyer’s patches were labeled with Texas Red bilosomes. Tissue morphology was well preserved by methanol immersion of both tissues; the two-photon-excited fluorescence signal was six times higher than in water and the depth of penetration of useful imaging was doubled. No modification of the microscope was needed except the provision of a ring to retain a sufficient depth of methanol for imaging

    Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development.

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    MLL-AF4+ infant B cell acute lymphoblastic leukemia is characterized by an early onset and dismal survival. It initiates before birth, and very little is known about the early stages of the disease's development. Using a conditional Mll-AF4-expressing mouse model in which fusion expression is targeted to the earliest definitive hematopoietic cells generated in the mouse embryo, we demonstrate that Mll-AF4 imparts enhanced B lymphoid potential and increases repopulation and self-renewal capacity during a putative pre-leukemic state. This occurs between embryonic days 12 and 14 and manifests itself most strongly in the lymphoid-primed multipotent progenitor population, thus pointing to a window of opportunity and a potential cell of origin. However, this state alone is insufficient to generate disease, with the mice succumbing to B cell lymphomas only after a long latency. Future analysis of the molecular details of this pre-leukemic state will shed light on additional events required for progression to acute leukemia.Core facilities at the Cambridge Institute for Medical Research are supported by Strategic Award WT100140 and equipment grant 093026; core facilities at the Edinburgh MRC Centre for Regenerative Medicine are supported by centre grant MR/K017047/1. This work was funded by a Bloodwise Bennett Senior Fellowship (10015 to K.O.), a Wellcome Trust Clinical PhD Studentship (097454/z/11/z to N.A.B.) the Gabrielle’s Angel Foundation for Cancer Research (to K.O.), and the Kay Kendall Leukaemia Fund (to K.O.).This is the final version of the article. It first appeared from Cell Press/Elsevier at http://dx.doi.org/10.1016/j.celrep.2016.06.046

    Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans

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    Acknowledgments We are grateful to the Ian Fraser Cytometry Centre and our Mass Spetrometry and qPCR Facilities for help with the flow cytometry, glutathione and qRT-PCR assays, respectively. We also thank our many colleagues in the CRISP Consortium and in the medical mycology and systems biology communities for insightful discussions. Funding: This work was supported by the CRISP project (Combinatorial Responses In Stress Pathways), which was funded by the UK Biotechnology and Biological Research Council (www.bbsrc.ac.uk): AJPB, KH, CG, ADM, NARG, MT, MCR. (Research Grants; BB/F00513X/1, BB/F005210/1-2). AJPB and JQ received additional support from the BBSRC (Research Grants; BB/K016393/1; BB/K017365/1). NARG and AJPB were also supported by the Wellcome Trust (www.wellcome.ac.uk), (Grants: 080088; 097377). AJPB was also supported by the European Research Council (http://erc.europa.eu/), (STRIFE Advanced Grant; ERC-2009-AdG-249793). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    Synthesis and structure of m-terphenyl thio-, seleno-, and telluroethers

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    Several routes for the synthesis of m-terphenyl thio-, seleno-, and telluroethers were investigated. m-Terphenyl iodides react with diphenyl diselenides or ditellurides (CsOH·H₂O, DMSO, 110 °C) to give the desired compounds in 19−84% yield which significantly extends the previously reported such reactions because o-benzyne cannot be an intermediate as previously suggested. However, the most general synthetic route was that involving reaction of 2,6-diaryl Grignard reagents with sulfur, selenium, or tellurium electrophiles. The m-terphenyl thio-, seleno-, and telluroethers were characterized spectroscopically and, in one case, by single-crystal X-ray analysis. Certain of these compounds showed atropisomerism and barriers for interconversion of isomers were determined by variable-temperature NMR spectroscopy. The barriers for interconverting the syn and anti atropisomers increase on going from the analogous S to Se to Te compounds. Calculations on this isomerization revealed that the barriers are due to rotation about the aryl−aryl bond and that the barriers for rotation about the aryl−chalcogen bond are much lower

    Mixed Candida albicans strain populations in colonized and infected mucosal tissues

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    Multilocus sequence typing of six Candida albicans colonies from primary isolation plates revealed instances of colony-to-colony microvariation and carriage of two strain types in single oropharyngeal and vaginal samples. Higher rates of colony variation in commensal samples suggest selection of types from mixed populations either in the shift to pathogenicity or the response to antifungal treatment

    Reduction of inequalities in health: assessing evidence-based tools

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    BACKGROUND: The reduction of health inequalities is a focus of many national and international health organisations. The need for pragmatic evidence-based approaches has led to the development of a number of evidence-based equity initiatives. This paper describes a new program that focuses upon evidence- based tools, which are useful for policy initiatives that reduce inequities. METHODS: This paper is based on a presentation that was given at the "Regional Consultation on Policy Tools: Equity in Population Health Reports," held in Toronto, Canada in June 2002. RESULTS: Five assessment tools were presented. 1. A database of systematic reviews on the effects of educational, legal, social, and health interventions to reduce unfair inequalities is being established through the Cochrane and Campbell Collaborations. 2 Decision aids and shared decision making can be facilitated in disadvantaged groups by 'health coaches' to help people become better decision makers, negotiators, and navigators of the health system; a pilot study in Chile has provided proof of this concept. 3. The CIET Cycle: Combining adapted cluster survey techniques with qualitative methods, CIET's population based applications support evidence-based decision making at local and national levels. The CIET map generates maps directly from survey or routine institutional data, to be used as evidence-based decisions aids. Complex data can be displayed attractively, providing an important tool for studying and comparing health indicators among and between different populations. 4. The Ottawa Equity Gauge is applying the Global Equity Gauge Alliance framework to an industrialised country setting. 5 The Needs-Based Health Assessment Toolkit, established to assemble information on which clinical and health policy decisions can be based, is being expanded to ensure a focus on distribution and average health indicators. CONCLUSION: Evidence-based planning tools have much to offer the goal of equitable health development

    Rapidly Decaying Supernova 2010X: A Candidate ".Ia" Explosion

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    We present the discovery, photometric and spectroscopic follow-up observations of SN 2010X (PTF 10bhp). This supernova decays exponentially with tau_d=5 days, and rivals the current recordholder in speed, SN 2002bj. SN 2010X peaks at M_r=-17mag and has mean velocities of 10,000 km/s. Our light curve modeling suggests a radioactivity powered event and an ejecta mass of 0.16 Msun. If powered by Nickel, we show that the Nickel mass must be very small (0.02 Msun) and that the supernova quickly becomes optically thin to gamma-rays. Our spectral modeling suggests that SN 2010X and SN 2002bj have similar chemical compositions and that one of Aluminum or Helium is present. If Aluminum is present, we speculate that this may be an accretion induced collapse of an O-Ne-Mg white dwarf. If Helium is present, all observables of SN 2010X are consistent with being a thermonuclear Helium shell detonation on a white dwarf, a ".Ia" explosion. With the 1-day dynamic-cadence experiment on the Palomar Transient Factory, we expect to annually discover a few such events.Comment: 6 pages, 5 figures; Minor Changes; Note correction in Fig 4 caption; published by ApJ
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