Protein Phosphatase 2C of Toxoplasma Gondii Interacts with Human SSRP1 and Negatively Regulates Cell Apoptosis

International audienceBiographical notes of the first authors: GAO Xue Juan, female, born in 1980, PhD, assistant researcher, majoring in protein-protein interaction and signaling pathways; FENG Jun Xia, female, born in 1989, majoring in pathogenic molecular mechanism of pathogenic microorganisms. Abstract Objective The protozoan Toxoplasma gondii expresses large amounts of a 37 kDa Type 2C serine-threonine phosphatase, the so-called TgPP2C which has been suggested to contribute to parasite growth regulation. Ectopic expression in mammalian cells also indicated that the enzyme could regulate growth and survival. In this study, we aimed to investigate the interaction of TgPP2C with human SSRP1 (structure-specific recognition protein 1) and the effects of TgPP2C on cell viability. Methods The yeast two hybrid system, His-tag pull-down and co-immunoprecipitation assays were used to confirm the interaction of TgPP2C with SSRP1 and determine the binding domain on SSRP1. The evaluation of cell apoptosis was performed using cleaved caspase-3 antibody and Annexin-V/PI kit combined with flow cytometry. Results We identified human SSRP1 as an interacting partner of TgPP2C. The C-terminal region of SSRP1 including the amino acids 471 to 538 was specifically mapped as the region responsible for interaction with TgPP2C. The overexpression of TgPP2C down-regulated cell apoptosis and negatively regulated apoptosis induced by DRB, casein kinase II (CKII) inhibitor, through enhanced interaction with SSRP1. Conclusion TgPP2C may be a parasitic factor capable of promoting cell survival through interaction with the host protein SSRP1, thereby creating a favorable environment for parasite growth

Genetic Risk and Atrial Fibrillation in Patients with Heart Failure

Aims: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure. Methods and results: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0–2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84–2.45, P = 2.15 × 10−24) in the total cohort, 2.08 (1.72–2.50, P = 1.30 × 10−14) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37–2.99, P = 4.37 × 10−4) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721. Conclusions: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence

Incidence and main factors associated with early unplanned hospital readmission among French medical inpatients aged 75 and over admitted through emergency units

Background: among elderly patients, readmission in the month following hospital discharge is a frequent occurrence which involves a risk of functional decline, particularly among frail subjects. While previous studies have identified risk factors of early readmission, geriatric syndromes, as markers of frailty have not been assessed as potential predictors. Objective: to evaluate the risk of early unplanned readmission, and to identify predictors in inpatients aged 75 and over, admitted to medical wards through emergency departments. Design: prospective multi-centre study. Setting: nine French hospitals. Subjects: one thousand three hundred and six medical inpatients, aged 75 and older admitted through emergency departments (SAFES cohort). Methods: using logistic regressions, factors associated with early unplanned re-hospitalisation (defined as first unplanned readmission in the thirty days after discharge) were identified using data from the first week of hospital index stay obtained by comprehensive geriatric assessment. Results: data from a thousand out of 1,306 inpatients were analysed. Early unplanned readmission occurred in 14.2% of inpatients and was not related with sociodemographic characteristics, comorbidity burden or cognitive impairment. Pressure sores (OR=2.05, 95% CI = 1.0-3.9), poor overall condition (OR = 2.01, 95% CI = 1.3-3.0), recent loss of ability for self-feeding (OR = 1.9, 95% CI = 1.2-2.9), prior hospitalisation during the last 3 months (OR = 1.6, 95% CI = 1.1-2.5) were found to be risk factors, while sight disorders appeared as negatively associated (OR = 0.5, 95% CI = 0.3--0.8). Conclusions: markers of frailty (poor overall condition, pressure sores, prior hospitalisation) or severe disability (for self-feeding) were the most important predictors of early readmission among elderly medical inpatients. Early identification could facilitate preventive strategies in risk grou

Трехкоординатный пьезокерамический сканер на биморфных пьезо-элементах для зондового наномикроскопа

Предложена и исследована конструкция пьезокерамического сканера для наномикроскопов на основе диморфных пьезоэлементов. Построена и исследована модель сканера при помощи программы MicroCap 7.0

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

Loss of independence in Katz's ADL ability in connection with an acute hospitalization: early clinical markers in French older people

Background: The preservation of autonomy and the ability of elderly to carry out the basic activities of daily living, beyond the therapeutic care of any pathologies, appears as one of the main objectives of care during hospitalization. Objectives: To identify early clinical markers associated with the loss of independence in elderly people in short stay hospitals. Methods: Among the 1,306 subjects making up the prospective and multicenter SAFEs cohort study (Sujet Agé Fragile: Évolution et suivi—Frail elderly subjects, evaluation and follow-up), 619 medical inpatients, not disabled at baseline and hospitalized through an emergency department were considered. Data used in a multinomial logistic regression were obtained through a comprehensive geriatric assessment (CGA) conducted in the first week of hospitalization. Dependency levels were assessed at baseline, at inclusion and at 30days using Katz's ADL index. Baseline was defined as the dependence level before occurrence of the event motivating hospitalization. To limit the influence of rehabilitation on the level of dependence, only stays shorter than 30days were considered. Results: About 514 patients were eligible, 15 died and 90 were still hospitalized at end point (n=619). Two-thirds of subjects were women, with a mean age of 83. At day 30 162 patients (31%) were not disabled; 61 (12%) were moderately disabled and 291 severely disabled (57%). No socio-demographic variables seemed to influence the day 30 dependence level. Lack of autonomy (odds ratio (OR)=1.9, 95% confidence interval (CI)=1.2-3.6), walking difficulties (OR=2.7, 95% CI=1.3-5.6), fall risk (OR=2.1, 95% CI=1.3-6.8) and malnutrition risk (OR=2.2, 95% CI=1.5-7.6) were found in multifactorial analysis to be clinical markers for loss of independence. Conclusions: Beyond considerations on the designing of preventive policies targeting the populations at risk that have been identified here, the identification of functional factors (lack of autonomy, walking difficulties, risk of falling) suggests above all that consideration needs to be given to the organization per se of the French geriatric hospital care system, and in particular to the relevance of maintaining sector-type segregation between wards for care of acute care and those involved in rehabilitatio