192 research outputs found

    СИМВОЛИКА «ХРАМА В СЕРДЦЕ» ВО ФРАНЦУЗСКОЙ РОМАНТИЧЕСКОЙ ЛИТЕРАТУРЕ 1820-Х ГГ.

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    В статье романтическая символика храма и сердца рассматривается в аналитической традиции Г. Башляра. Французская романтическая поэзия перших десятиріч ХІХ ст. сохранила руссоистскую стилистику, однако актуализировала в новой мифопоэтической форме стихию человеческих чувств в их связи со стихиями природы и трансендентностью

    Batch studies on the biodegradation potential of Paracetamol, Fluoxetine and 17α-Ethinylestradiol by the Micrococcus yunnanensis Strain TJPT4 recovered from marine organisms

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    The emerging pollutants paracetamol, fluoxetine and ethinylestradiol are inefficiently removed by conventional wastewater treatments, entering in aquatic environments in which they are hazardous. Aiming for the obtention of bacteria with the capacity for environmental bioremediation, eight bacteria were isolated from two consortia recovered from Hymedesmia versicolor and Filograna implexa marine organisms which exhibited a high-paracetamol-removal capacity. The isolates that displayed the ability to grow in the presence of 100 mg/L paracetamol as the sole carbon source were assigned to Paenibacillus, Micrococcus and Microbacterium genera. The isolate assigned to the Micrococcus yunnanensis strain TJPT4 presented the best performance, degrading 93 ± 4% of 15 mg/L paracetamol as the sole carbon source after 360 h, and was also apparently able to degrade the produced metabolites. This strain was able to remove 82.1 ± 0.9% of 16 mg/L fluoxetine after 504 h, mainly by adsorption, but apparently a biodegradation contribution also occurred. This strain was able to remove 66.6 ± 0.2% of 13 mg/L 17α-ethinylestradiol after 360 h. As far as is known, Micrococcus yunnanensis is for the first time recovered/identified in Filograna implexa, presenting a high drug removal efficiency, thereby becoming a great candidate for treatment processes (e.g., bioaugmentation), especially in the presence of saline intrusions.info:eu-repo/semantics/publishedVersio

    Second-language learning and changes in the brain

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    International audiencePresumably, second-language (L2) learning is mediated by changes in the brain. Little is known about what changes in the brain, how the brain changes, or when these changes occur during learning. Here, we illustrate by way of example how modern brain-based methods can be used to discern some of the changes that occur during L2 learning. Preliminary results from three studies indicate that classroom based L2 instruction can result in changes in the brain's electrical activity, in the location of this activity within the brain, and in the structure of the learners' brains. These changes can occur during the earliest stages of L2 acquisition

    Phosphatidylinositide 3-kinase (PI3K) and PI3K-related kinase (PIKK) activity contributes to radioresistance in thyroid carcinomas.

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    Anaplastic (ATC) and certain follicular thyroid-carcinomas (FTCs) are radioresistant. The Phosphatidylinositide 3-kinase (PI3K) pathway is commonly hyperactivated in thyroid-carcinomas. PI3K can modify the PI3K-related kinases (PIKKs) in response to radiation: How PIKKs interact with PI3K and contribute to radioresistance in thyroid-carcinomas is unknown. Further uncertainties exist in how these interactions function under the radioresistant hypoxic microenvironment. Under normoxia/anoxia, ATC (8505c) and FTC (FTC-133) cells were irradiated, with PI3K-inhibition (via GDC-0941 and PTEN-reconstitution into PTEN-null FTC-133s) and effects on PIKK-activation, DNA-damage, clonogenic-survival and cell cycle, assessed. FTC-xenografts were treated with 5 × 2 Gy, ± 50 mg/kg GDC-0941 (twice-daily; orally) for 14 days and PIKK-activation and tumour-growth assessed. PIKK-expression was additionally assessed in 12 human papillary thyroid-carcinomas, 13 FTCs and 12 ATCs. GDC-0941 inhibited radiation-induced activation of Ataxia-telangiectasia mutated (ATM), ATM-and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Inhibition of ATM and DNA-PKcs was PI3K-dependent, since activation was reduced in PTEN-reconstituted FTC-133s. Inhibition of PIKK-activation was greater under anoxia: Consequently, whilst DNA-damage was increased and prolonged under both normoxia and anoxia, PI3K-inhibition only reduced clonogenic-survival under anoxia. GDC-0941 abrogated radiation-induced cell cycle arrest, an effect most likely linked to the marked inhibition of ATR-activation. Importantly, GDC-0941 inhibited radiation-induced PIKK-activation in FTC-xenografts leading to a significant increase in time taken for tumours to triple in size: 26.5 ± 5 days (radiation-alone) versus 31.5 ± 5 days (dual-treatment). PIKKs were highly expressed across human thyroid-carcinoma classifications, with ATM scoring consistently lower. Interestingly, some loss of ATM and DNA-PKcs was observed. These data provide new insight into the mechanisms of hypoxia-associated radioresistance in thyroid-carcinoma

    Former à s’informer : développer l’esprit critique ! Comment éduquer et accompagner les adolescents et les jeunes adultes dans l’univers médiatique contemporain pour les aider à grandir ?

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    Les contenus pédagogiques ont été réalisés dans le cadre du projet Former des médiateurs EMI pour adolescents et jeunes adultes, déposé en 2020 par l’Enssib et l’Inspé Université Claude Bernard Lyon 1. Ce projet s’inscrit dans le Plan EMI développé et financé par le Ministère de la Culture

    Intermolecular Photocatalytic Chemo‐, Stereo‐ and Regioselective Thiol–Yne–Ene Coupling Reaction

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    The first example of an intermolecular thiol–yne–ene coupling reaction is reported for the one-pot construction of C−S and C−C bonds. Thiol–yne–ene coupling opens a new dimension in building molecular complexity to access densely functionalized products. The employment of Eosin Y/DBU/MeOH photocatalytic system suppresses hydrogen atom transfer (HAT) and associative reductant upconversion (via C−S three-electron σ-bond formation). Investigation of the reaction mechanism by combining online ESI-UHRMS, EPR spectroscopy, isotope labeling, determination of quantum yield, cyclic voltammetry, Stern–Volmer measurements and computational modeling revealed a unique photoredox cycle with four radical-involving stages. As a result, previously unavailable products of the thiol–yne–ene reaction were obtained in good yields with high selectivity. They can serve as stable precursors for synthesizing synthetically demanding activated 1,3-dienes

    A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs.

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    Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the β-MSH and β-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.We are grateful to Rachel Moxon of Guide Dogs UK for collecting the assistance dog samples; Stephen J Sharp of the MRC Epidemiology Unit for his statistical advice; Jens Häggström, Karin Hultin Jäderlund and Berndt Klingeborn for the Swedish dog samples; Anne White for efforts to develop a canine beta MSH assay and adaptation of her original for figure 1b; and the Dogslife Consortium for samples from British Labrador retrievers (supported by an Institute Core Strategic Grant from the BBSRC to the Roslin Institute). A full list of the investigators who contributed to the Dogslife project is available from www.dogslife.ac.uk/who-runs-dogslife. AJG's academic post at the University of Liverpool is financially supported by Royal Canin. The work was primarily supported by the Wellcome Trust (Senior Investigator Award 095515/Z/11/Z and Strategic Award 100574/Z/12/Z), MRC (MRC Metabolic Diseases Unit, award 4050281695 and MRC_MC_UU_12012/5), and Dogs Trust. The authors would like to thank all the veterinary surgeons and nurses, owners and dogs who contributed samples.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.cmet.2016.04.01

    Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study

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    BACKGROUND: Most neonatal and infantile-onset epilepsies have presumed genetic aetiologies, and early genetic diagnoses have the potential to inform clinical management and improve outcomes. We therefore aimed to determine the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in this population. METHODS: We conducted an international, multicentre, cohort study (Gene-STEPS), which is a pilot study of the International Precision Child Health Partnership (IPCHiP). IPCHiP is a consortium of four paediatric centres with tertiary-level subspecialty services in Australia, Canada, the UK, and the USA. We recruited infants with new-onset epilepsy or complex febrile seizures from IPCHiP centres, who were younger than 12 months at seizure onset. We excluded infants with simple febrile seizures, acute provoked seizures, known acquired cause, or known genetic cause. Blood samples were collected from probands and available biological parents. Clinical data were collected from medical records, treating clinicians, and parents. Trio genome sequencing was done when both parents were available, and duo or singleton genome sequencing was done when one or neither parent was available. Site-specific protocols were used for DNA extraction and library preparation. Rapid genome sequencing and analysis was done at clinically accredited laboratories, and results were returned to families. We analysed summary statistics for cohort demographic and clinical characteristics and the timing, diagnostic yield, and clinical impact of rapid genome sequencing. FINDINGS: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 100 infants with new-onset epilepsy, of whom 41 (41%) were girls and 59 (59%) were boys. Median age of seizure onset was 128 days (IQR 46-192). For 43 (43% [binomial distribution 95% CI 33-53]) of 100 infants, we identified genetic diagnoses, with a median time from seizure onset to rapid genome sequencing result of 37 days (IQR 25-59). Genetic diagnosis was associated with neonatal seizure onset versus infantile seizure onset (14 [74%] of 19 vs 29 [36%] of 81; p=0·0027), referral setting (12 [71%] of 17 for intensive care, 19 [44%] of 43 non-intensive care inpatient, and 12 [28%] of 40 outpatient; p=0·0178), and epilepsy syndrome (13 [87%] of 15 for self-limited epilepsies, 18 [35%] of 51 for developmental and epileptic encephalopathies, 12 [35%] of 34 for other syndromes; p=0·001). Rapid genome sequencing revealed genetic heterogeneity, with 34 unique genes or genomic regions implicated. Genetic diagnoses had immediate clinical utility, informing treatment (24 [56%] of 43), additional evaluation (28 [65%]), prognosis (37 [86%]), and recurrence risk counselling (all cases). INTERPRETATION: Our findings support the feasibility of implementation of rapid genome sequencing in the clinical care of infants with new-onset epilepsy. Longitudinal follow-up is needed to further assess the role of rapid genetic diagnosis in improving clinical, quality-of-life, and economic outcomes. FUNDING: American Academy of Pediatrics, Boston Children's Hospital Children's Rare Disease Cohorts Initiative, Canadian Institutes of Health Research, Epilepsy Canada, Feiga Bresver Academic Foundation, Great Ormond Street Hospital Charity, Medical Research Council, Murdoch Children's Research Institute, National Institute of Child Health and Human Development, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, One8 Foundation, Ontario Brain Institute, Robinson Family Initiative for Transformational Research, The Royal Children's Hospital Foundation, University of Toronto McLaughlin Centre

    Methods to determine the interactions of micro- and nanoparticles with mucus

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    The present review provides an overview of methods and techniques for studying interactions of micro- and nanoparticulate drug delivery system with mucus. Nanocarriers trapped by mucus are featuring a change in particle size and zeta potential that can be utilized to predict their mucus permeation behavior. Furthermore, interactions between nanoparticulate drug delivery systems and mucus layer modify the viscoelasticity of mucus which can be detected via rheological studies and quartz crystal microbalance with dissipation monitoring (QCM-D) analysis. To have a closer look at molecular interactions between drug carrier and mucus small-angle neutron scattering (SANS) is an appropriate analysis technique. Moreover, different methods to determine particle diffusion in mucus such as the newly established Transwell diffusion system, rotating silicone tube technique, multiple-particle tracking (MPT) and diffusion NMR are summarized within this review. The explanations and discussed pros and cons of collated methods and techniques should provide a good starting point for all those looking forward to move in this interesting field
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