3,943 research outputs found

    The Nonstructural Proteins of Nipah Virus Play a Key Role in Pathogenicity in Experimentally Infected Animals

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    Nipah virus (NiV) P gene encodes P protein and three accessory proteins (V, C and W). It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V−), rNiV(C−), and rNiV(W−), respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V−) and rNiV(C−) were lower than the other recombinants. The rNiV(V−), rNiV(C−) and rNiV(W−) suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V−) and rNiV(C−) but not the rNiV(W−) virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo

    The second data release of the INT Photometric Ha Survey of the Northern Galactic Plane (IPHAS DR2)

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    The INT/WFC Photometric Hα Survey of the Northern Galactic Plane (IPHAS) is a 1800 deg2 imaging survey covering Galactic latitudes |b| < 5° and longitudes ℓ = 30°–215° in the r, i, and Hα filters using the Wide Field Camera (WFC) on the 2.5-m Isaac Newton Telescope (INT) in La Palma. We present the first quality-controlled and globally calibrated source catalogue derived from the survey, providing single-epoch photometry for 219 million unique sources across 92 per cent of the footprint. The observations were carried out between 2003 and 2012 at a median seeing of 1.1 arcsec (sampled at 0.33 arcsec pixel−1) and to a mean 5σ depth of 21.2 (r), 20.0 (i), and 20.3 (Hα) in the Vega magnitude system. We explain the data reduction and quality control procedures, describe and test the global re-calibration, and detail the construction of the new catalogue. We show that the new calibration is accurate to 0.03 mag (root mean square) and recommend a series of quality criteria to select accurate data from the catalogue. Finally, we demonstrate the ability of the catalogue's unique (r − Hα, r − i) diagram to (i) characterize stellar populations and extinction regimes towards different Galactic sightlines and (ii) select and quantify Hα emission-line objects. IPHAS is the first survey to offer comprehensive CCD photometry of point sources across the Galactic plane at visible wavelengths, providing the much-needed counterpart to recent infrared surveys

    Knee instruments and rating scales designed to measure outcomes

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    In this article, the knee instruments and rating scales that are designed to measure outcomes are revised. Although the International Knee Documentation Committee Subjective Knee Form can be used as a general knee measure, no instrument is currently universally applicable across the spectrum of knee disorders and patient groups. Clinicians and researchers looking to use a patient-based score for measurement of outcomes must consider the specific patient population in which it has been evaluated. The Western Ontario and McMaster Universities Osteoarthritis Index is recommended for the evaluation of treatment effect in persons with osteoarthritis (OA). This is a generic health status questionnaire that contains 36 items, is widely used, and easy to complete. The Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire evaluates the functional status and quality of life (QoL) of patients with any type of knee injury who are at increased risk of developing OA; i.e., patients with anterior cruciate ligament (ACL) injury, meniscus injury, or chondral injury. So far, the KOOS questionnaire has been validated for several orthopedic procedures such as total knee arthroplasty, ACL reconstruction, and meniscectomy. The utilization of QoL questionnaires is crucial to the adequate assessment of a number of orthopedic procedures of the knee. The questionnaires are generally well accepted by the patients and open up new perspectives in the analysis of prognostic factors for optimal QoL of patients undergoing knee surgery

    Investigating the association between obesity and asthma in 6- to 8-year-old Saudi children:a matched case-control study

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    Background: Previous studies have demonstrated an association between obesity and asthma, but there remains considerable uncertainty about whether this reflects an underlying causal relationship. Aims: To investigate the association between obesity and asthma in pre-pubertal children and to investigate the roles of airway obstruction and atopy as possible causal mechanisms. Methods: We conducted an age- and sex-matched case–control study of 1,264 6- to 8-year-old schoolchildren with and without asthma recruited from 37 randomly selected schools in Madinah, Saudi Arabia. The body mass index (BMI), waist circumference and skin fold thickness of the 632 children with asthma were compared with those of the 632 control children without asthma. Associations between obesity and asthma, adjusted for other potential risk factors, were assessed separately in boys and girls using conditional logistic regression analysis. The possible mediating roles of atopy and airway obstruction were studied by investigating the impact of incorporating data on sensitisation to common aeroallergens and measurements of lung function. Results: BMI was associated with asthma in boys (odds ratio (OR)=1.14, 95% confidence interval (CI), 1.08–1.20; adjusted OR=1.11, 95% CI, 1.03–1.19) and girls (OR=1.37, 95% CI, 1.26–1.50; adjusted OR=1.38, 95% CI, 1.23–1.56). Adjusting for forced expiratory volume in 1 s had a negligible impact on these associations, but these were attenuated following adjustment for allergic sensitisation, particularly in girls (girls: OR=1.25; 95% CI, 0.96–1.60; boys: OR=1.09, 95% CI, 0.99–1.19). Conclusions: BMI is associated with asthma in pre-pubertal Saudi boys and girls; this effect does not appear to be mediated through respiratory obstruction, but in girls this may at least partially be mediated through increased risk of allergic sensitisation

    Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

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    The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

    Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

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    Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

    A perspective on radical transformations to sustainability: resistances, movements and alternatives

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    A transformation to sustainability calls for radical and systemic societal shifts. Yet what this entails in practice and who the agents of this radical transformation are require further elaboration. This article recenters the role of environmental justice movements in transformations, arguing that the systemic, multi-dimensional and intersectional approach inherent in EJ activism is uniquely placed to contribute to the realization of equitable sustainable futures. Based on a perspective of conflict as productive, and a “conflict transformation” approach that can address the root issues of ecological conflicts and promote the emergence of alternatives, we lay out a conceptual framework for understanding transformations through a power analysis that aims to confront and subvert hegemonic power relations; that is, multi-dimensional and intersectional; balancing ecological concerns with social, economic, cultural and democratic spheres; and is multi-scalar, and mindful of impacts across place and space. Such a framework can help analyze and recognize the contribution of grassroots EJ movements to societal transformations to sustainability and support and aid radical transformation processes. While transitions literature tends to focus on artifacts and technologies, we suggest that a resistance-centred perspective focuses on the creation of new subjectivities, power relations, values and institutions. This recenters the agency of those who are engaged in the creation and recuperation of ecological and new ways of being in the world in the needed transformation
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