1,266 research outputs found

    Clustered Intracellular Salmonella enterica Serovar Typhimurium blocks host cell cytokinesis

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    Several bacterial pathogens and viruses interfere with the cell cycle of their host cells to enhance virulence. This is especially apparent in bacteria that colonize the gut epithelium, where inhibition of the cell cycle of infected cells enhances the intestinal colonization. We found that intracellular Salmonella enterica serovar Typhimurium induced the binucleation of a large proportion of epithelial cells by 14 h postinvasion and that the effect was dependent on an intact Salmonella pathogenicity island 2 (SPI-2) type 3 secretion system. The SPI-2 effectors SseF and SseG were required to induce binucleation. SseF and SseG are known to maintain microcolonies of Salmonella-containing vacuoles close to the microtubule organizing center of infected epithelial cells. During host cell division, these clustered microcolonies prevented the correct localization of members of the chromosomal passenger complex and mitotic kinesin-like protein 1 and consequently prevented cytokinesis. Tetraploidy, arising from a cytokinesis defect, is known to have a deleterious effect on subsequent cell divisions, resulting in either chromosomal instabilities or cell cycle arrest. In infected mice, proliferation of small intestinal epithelial cells was compromised in an SseF/SseG-dependent manner, suggesting that cytokinesis failure caused by S. Typhimurium delays epithelial cell turnover in the intestine

    Predictors of Patient-Reported Pain and Functional Outcomes Over 10 Years After Primary Total Knee Arthroplasty: A Prospective Cohort Study.

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    Background This study aimed to identify preoperative predictors of patient-reported outcomes after total knee replacement (TKR) and to investigate their association with the outcomes over time. Methods We used data from 2,080 patients from the Knee Arthroplasty Trial (KAT) who received primary TKR in the UK between July 1999 and January 2003. The primary outcome measure was the Oxford Knee Score (OKS) collected annually over 10 years after TKR. Preoperative predictors included a range of patient characteristics and clinical conditions. Mixed-effects linear regression model analysis of repeated measurements was used to identify predictors of OKS overall score, pain and function subscale scores over 10 years, separately. Results Worse preoperative OKS score, worse mental well-being, BMI>35 kg/m^2, living in the most deprived areas, higher American Society of Anaesthesiologists grade, presence of comorbidities, and history of previous knee surgery were associated with worse OKS overall score over 10 years after surgery. The same predictors were identified for pain and function subscale scores, and for both long-term (10 years) and short-/mid-term outcomes (1 and 5 years). However, fitted models explained more variations in function and shorter-term outcomes than in pain and longer-term outcomes, respectively. Conclusion The same predictors were identified for pain and functional outcomes over both short-tomedium term and long term after TKR. Within the factors identified, functional and shorter-term outcomes were more predictable than pain and longer-term outcomes, respectively. Regardless of their preoperative characteristics, on average, patients achieved substantial improvement in pain over time, though improvement for function was less prominent. </p

    A BODIPY small molecule as hole transporting material for efficient perovskite solar cells

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    BODIPY-based materials are well known for their outstanding chemical and photo-stability as well as their ease of synthesis and tunability of their frontier molecular orbitals. These are attractive features for hole transporting materials (HTMs) for perovskite solar cells (PSCs) that could help improve device stability and cost. In this paper, we report the straightforward synthesis of a new BODIPY small molecule, PTZ-PTZ-BDP, functionalised with phenothiazine moieties in both the meso and α positions giving rise to a Y-shaped structure. As estimated by DFT calculations, and confirmed by electrochemical and ambient photoemission spectroscopy studies, PTZ-PTZ-BDP presents appropriate energy levels suitable for its use as a HTM in PSCs. Electrochemical measurements also reveal several redox processes with excellent reversibility. Systematic evaluation of its performance as HTM in n–i–p PSC with and without dopants was conducted and the device parameters compared with commonly used HTMs of spiro-OMeTAD and PTAA. The CH3NH3PbI3 based PSCs incorporating simple solution processed PTZ-PTZ-BDP as HTM demonstrated a champion power conversion efficiency of 14.6%, matched in performance and shelf-life stability to complex and expensive state-of-the-art HTMs, showing that BODIPY based HTMs are a promising direction for perovskite solar cells

    Thermodynamic properties of excess-oxygen-doped La2CuO4.11 near a simultaneous transition to superconductivity and long-range magnetic order

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    We have measured the specific heat and magnetization {\it versus} temperature in a single crystal sample of superconducting La2_{2}CuO4.11_{4.11} and in a sample of the same material after removing the excess oxygen, in magnetic fields up to 15 T. Using the deoxygenated sample to subtract the phonon contribution, we find a broad peak in the specific heat, centered at 50 K. This excess specific heat is attributed to fluctuations of the Cu spins possibly enhanced by an interplay with the charge degrees of freedom, and appears to be independent of magnetic field, up to 15 T. Near the superconducting transition TcT_{c}(HH=0)= 43 K, we find a sharp feature that is strongly suppressed when the magnetic field is applied parallel to the crystallographic c-axis. A model for 3D vortex fluctuations is used to scale magnetization measured at several magnetic fields. When the magnetic field is applied perpendicular to the c-axis, the only observed effect is a slight shift in the superconducting transition temperature.Comment: 8 pages, 8 figure

    A mathematical analysis of the evolution of perturbations in a modified Chaplygin gas model

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    One approach in modern cosmology consists in supposing that dark matter and dark energy are different manifestations of a single `quartessential' fluid. Following such idea, this work presents a study of the evolution of perturbations of density in a flat cosmological model with a modified Chaplygin gas acting as a single component. Our goal is to obtain properties of the model which can be used to distinguish it from another cosmological models which have the same solutions for the general evolution of the scale factor of the universe, without the construction of the power spectrum. Our analytical results, which alone can be used to uniquely characterize the specific model studied in our work, show that the evolution of the density contrast can be seen, at least in one particular case, as composed by a spheroidal wave function. We also present a numerical analysis which clearly indicates as one interesting feature of the model the appearence of peaks in the evolution of the density constrast.Comment: 21 pages, accepted for publication in General Relativity and Gravitatio

    Transfer learning for galaxy morphology from one survey to another

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    © 2018 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society.Deep Learning (DL) algorithms for morphological classification of galaxies have proven very successful, mimicking (or even improving) visual classifications. However, these algorithms rely on large training samples of labelled galaxies (typically thousands of them). A key question for using DL classifications in future Big Data surveys is how much of the knowledge acquired from an existing survey can be exported to a new dataset, i.e. if the features learned by the machines are meaningful for different data. We test the performance of DL models, trained with Sloan Digital Sky Survey (SDSS) data, on Dark Energy survey (DES) using images for a sample of ∌\sim5000 galaxies with a similar redshift distribution to SDSS. Applying the models directly to DES data provides a reasonable global accuracy (∌\sim 90%), but small completeness and purity values. A fast domain adaptation step, consisting in a further training with a small DES sample of galaxies (∌\sim500-300), is enough for obtaining an accuracy > 95% and a significant improvement in the completeness and purity values. This demonstrates that, once trained with a particular dataset, machines can quickly adapt to new instrument characteristics (e.g., PSF, seeing, depth), reducing by almost one order of magnitude the necessary training sample for morphological classification. Redshift evolution effects or significant depth differences are not taken into account in this study.Peer reviewedFinal Accepted Versio

    Association of Undifferentiated Dyspnea in Late Life With Cardiovascular and Noncardiovascular Dysfunction: A Cross-sectional Analysis From the ARIC Study

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    Importance: Undifferentiated dyspnea is common in late life, but the relative contribution of subclinical cardiac dysfunction is unknown. Impairments in cardiac structure and function may be characteristics of undifferentiated dyspnea in elderly people, providing potential insights into occult heart failure (HF). Objective: To quantify the association of undifferentiated dyspnea with cardiac dysfunction after accounting for other potential contributors. Design, Setting, and Participants: This cross-sectional study used data from Atherosclerosis Risk in Communities study participants 65 years and older who attended the fifth study visit (from 2011 to 2013) and had not been diagnosed with HF, chronic obstructive pulmonary disease, morbid obesity, or severe kidney disease. Analyses were conducted from October 2017 to June 2018. Exposures: Dyspnea measured using the modified Medical Research Council scale, with a score less than 2 classified as none to mild and a score of 2 or more classified as moderate to severe. Main Outcomes and Measures: Using multivariable logistic regression, the association of undifferentiated dyspnea was defined using cardiac structure, systolic and diastolic function, pulmonary pressure (echocardiography), pulmonary function (spirometry), glomerular filtration rate, hemoglobin, body mass index, depression, and physical performance. The population-attributable risk was calculated for each dysfunction metric. Results: Among 4342 participants (mean [SD] age, 75.9 [5.0] years; 2533 [58.3%] women), 1173 (27.0%) had undifferentiated dyspnea. Moderate to severe dyspnea was present in 574 participants (13.2%) and was associated with left ventricular (LV) hypertrophy (odds ratio [OR], 1.53; 95% CI, 1.25-1.87; P < .001) and LV diastolic (OR, 1.46; 95% CI, 1.20-1.78; P < .001) and systolic (OR, 1.28; 95% CI, 1.05-1.56; P = .02) dysfunction. Moderate to severe dyspnea was also associated with obstructive (OR, 1.59; 95% CI, 1.28-1.99; P < .001) and restrictive (OR, 2.56; 95% CI, 1.99-3.27; P < .001) findings on spirometry, renal impairment (OR, 1.32; 95% CI, 1.08-1.61; P = .01), anemia (OR, 1.72; 95% CI, 1.39-2.12; P < .001), lower (OR, 2.77; 95% CI, 2.18-3.51; P < .001) and upper (OR, 1.82; 95% CI, 1.49-2.23; P < .001) extremity weakness, depression (OR, 3.01; 95% CI, 2.24-4.25; P < .001), and obesity (OR, 2.35; 95% CI, 1.95-2.83; P < .001). After accounting for these, moderate to severe dyspnea was associated with LV hypertrophy (OR, 1.30; 95% CI, 1.01-1.67; P = .04) and was not associated with systolic or diastolic function. In contrast, in the fully adjusted model, other organ system measures were associated with dyspnea, except for glomerular filtration rate and grip strength. The population-attributable risk of dyspnea associated with obesity alone was 22.6% compared with 5.8% for LV hypertrophy. Conclusions and Relevance: Undifferentiated dyspnea is multifactorial in older adults, and this study showed an association with obesity. When accounting for other relevant organ systems, cardiovascular function poorly discriminated those with vs those without dyspnea. Therefore, dyspnea should not be assumed to represent occult HF in this population

    A Model for the Development of the Rhizobial and Arbuscular Mycorrhizal Symbioses in Legumes and Its Use to Understand the Roles of Ethylene in the Establishment of these two Symbioses

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    We propose a model depicting the development of nodulation and arbuscular mycorrhizae. Both processes are dissected into many steps, using Pisum sativum L. nodulation mutants as a guideline. For nodulation, we distinguish two main developmental programs, one epidermal and one cortical. Whereas Nod factors alone affect the cortical program, bacteria are required to trigger the epidermal events. We propose that the two programs of the rhizobial symbiosis evolved separately and that, over time, they came to function together. The distinction between these two programs does not exist for arbuscular mycorrhizae development despite events occurring in both root tissues. Mutations that affect both symbioses are restricted to the epidermal program. We propose here sites of action and potential roles for ethylene during the formation of the two symbioses with a specific hypothesis for nodule organogenesis. Assuming the epidermis does not make ethylene, the microsymbionts probably first encounter a regulatory level of ethylene at the epidermis–outermost cortical cell layer interface. Depending on the hormone concentrations there, infection will either progress or be blocked. In the former case, ethylene affects the cortex cytoskeleton, allowing reorganization that facilitates infection; in the latter case, ethylene acts on several enzymes that interfere with infection thread growth, causing it to abort. Throughout this review, the difficulty of generalizing the roles of ethylene is emphasized and numerous examples are given to demonstrate the diversity that exists in plants
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