Design and synthesis of new non nucleoside inhibitors of DNMT3A.

DNA methylation, an epigenetic modification regulating gene expression, is a promising target in cancer. In an effort to identify new non nucleosidic inhibitors of DNA methyltransferases, the enzymes responsible for DNA methylation, we carried out a high-throughput screening of 66,000 chemical compounds based on an enzymatic assay against catalytic DNMT3A. A family of propiophenone derivatives was identified.

Models based on ultraviolet spectroscopy, polyphenols, oligosaccharides and polysaccharides for prediction of wine astringency.

Astringency elicited by tannins is usually assessed by tasting. Alternative methods involving tannin precipitation have been proposed, but they remain time-consuming. Our goal was to propose a faster method and investigate the links between wine composition and astringency.

GP responses to price regulation: evidence from a French nationwide reform.

This paper uses a French reform to evaluate the impacts of overbilling restrictions on general practitioner (GP) care provision, fees and incomes. Since 1990, this reform has introduced conditions self-employed GPs must fulfil to be permitted to bill freely. We exploit 2005 and 2008 public health insurance administrative data on GP activity and fees.

Dendritic Cell-Mediated Phagocytosis but Not Immune Activation Is Enhanced by Plasmin.

Removal of dead cells in the absence of concomitant immune stimulation is essential for tissue homeostasis. We recently identified an injury-induced protein misfolding event that orchestrates the plasmin-dependent proteolytic degradation of necrotic cells. As impaired clearance of dead cells by the innate immune system predisposes to autoimmunity, we determined whether plasmin could influence endocytosis and immune cell stimulation by dendritic cells - a critical cell that links the innate and adaptive immune systems.

Investigating vision in schizophrenia through responses to humorous stimuli.

The visual environment of humans contains abundant ambiguity and fragmentary information. Therefore, an early step of vision must disambiguate the incessant stream of information. Humorous stimuli produce a situation that is strikingly analogous to this process: Funniness is associated with the incongruity contained in a joke, pun, or cartoon.

Resilience in Pre-Columbian Caribbean House-Building: Dialogue Between Archaeology and Humanitarian Shelter.

This paper responds to questions posed by archaeologists and engineers in the humanitarian sector about relationships between shelter, disasters and resilience. Enabled by an increase in horizontal excavations combined with high-resolution settlement data from excavations in the Dominican Republic, the paper presents a synthesis of Caribbean house data spanning a millennium (1400 BP- 450 BP). An analysis of architectural traits identify the house as an institution that constitutes and catalyses change in an emergent and resilient pathway.

The psychophysiology of mixed emotional states: Internal and external replicability analysis of a direct replication study.

The replicability of emotion-related physiological changes constitutes a fundamental issue in affective science. We undertook a direct replication of the physiological differentiation of amusement, disgust, and a mixed emotional state as previously reported (Kreibig, Samson, & Gross, 2013). In the current study, 48 women watched 54 amusing, disgusting, and mixed emotional film clips while cardiovascular, electrodermal, and respiratory measures were obtained.

Anticancer activity of koningic acid and semisynthetic derivatives.

A screening program aimed at discovering novel anticancer agents based on natural products led to the selection of koningic acid (KA), known as a potent inhibitor of glycolysis. A method was set up to produce this fungal sesquiterpene lactone in large quantities by fermentation, thus allowing (i) an extensive analysis of its anticancer potential in vitro and in vivo and (ii) the semi-synthesis of analogues to delineate structure-activity relationships. KA was characterized as a potent, but non-selective cytotoxic agent, active under both normoxic and hypoxic conditions and inactive in the A549 lung cancer xenograft model.

Eliciting positive, negative and mixed emotional states: A film library for affective scientists.

We describe the creation of a film library designed for researchers interested in positive (amusing), negative (repulsive), mixed (amusing and repulsive) and neutral emotional states. Three hundred 20- to 33-second film clips videotaped by amateurs were selected from video-hosting websites and screened in laboratory studies by 75 female participants on self-reported amusement and repulsion (Experiments 1 and 2). On the basis of pre-defined cut-off values, 51 positive, 39 negative, 59 mixed and 50 neutral film clips were selected.

Oversewing staple lines to prevent anastomotic complications in primary ileocolic resections for Crohn's disease.

Background: Oversewing staple lines may be a novel way to reduce anastomotic complications after primary ileocolic resections for Crohn's disease (CD).

Study Design: This is a single-institution, non-concurrent cohort study of CD patients undergoing primary ileocolic resections (ICR) with stapled anastomoses from 2007 to 2013. Demographic and clinical characteristics were collected.

Maladaptive Behavior in Autism Spectrum Disorder: The Role of Emotion Experience and Emotion Regulation.

Maladaptive behavior is common in Autism Spectrum Disorder (ASD). However, the factors that give rise to maladaptive behavior in this context are not well understood. The present study examined the role of emotion experience and emotion regulation in maladaptive behavior in individuals with ASD and typically developing (TD) participants.

Chronic exposure to neonicotinoids increases neuronal vulnerability to mitochondrial dysfunction in the bumblebee (Bombus terrestris).

The global decline in the abundance and diversity of insect pollinators could result from habitat loss, disease, and pesticide exposure. The contribution of the neonicotinoid insecticides (e.g.

Dysregulation between emotion and theory of mind networks in borderline personality disorder.

Individuals with borderline personality disorder (BPD) commonly display deficits in emotion regulation, but findings in the area of social cognitive (e.g., theory of mind, ToM) capacities have been heterogeneous.

Emotion regulation in autism spectrum disorder: evidence from parent interviews and children's daily diaries.

Background: Although emotion dysregulation is not a defining feature of Autism Spectrum Disorder (ASD), there is a growing consensus that emotional problems play a prominent role in this disorder.

Methods: The present study examined a wide range of emotion regulation (ER) strategies in 32 individuals with ASD compared to 31 group-matched typically developing (TD) participants in three emotional domains (anger, anxiety, and amusement). Parents of individuals with ASD and TD individuals were interviewed about their child's emotional experience and the use and efficacy of 10 ER strategies.

NMR structure of the water soluble Aβ17-34 peptide.

Alzheimer's disease is the most common neurodegenerative disorder in the world. Its most significant symptoms are memory loss and decrease in cognition. Alzheimer's disease is characterized by aggregation of two proteins in the brain namely Aβ (amyloid β) and tau.

5-Hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT3 receptor resensitization due to its subsequent release.

The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT3) receptors. We report that recombinantly expressed 5-HT3 receptor binding sites are reduced by chronic exposure to 5-HT (IC50 of 154.0 ± 45.

PHI-DAC: protein homology database through dihedral angle conservation.

Unlabelled: Finding related conformations in the Protein Data Bank is essential in many areas of bioscience. To assist this task, we designed a dihedral angle database for searching protein segment homologs. The search engine relies on encoding of the protein coordinates into text characters representing amino acid sequence, φ and ψ dihedral angles.

Normal mode dynamics of voltage-gated K(+) channels: gating principle, opening mechanism, and inhibition.

Voltage-dependent potassium channels open in response to changes in membrane potential and become partially inactivated upon binding of inhibitors. Here we calculate normal mode motion of two voltage-dependent K(+) channels, KvAP and Shaker, and their complexes with inhibitors and address the gating principle, opening mechanism, and inhibition. The normal modes indicate that pore expansion and channel opening is correlated with a displacement of the arginine gating charges and a tilting of the voltage-sensor paddles.

Activated platelets rescue apoptotic cells via paracrine activation of EGFR and DNA-dependent protein kinase.

Platelet activation is a frontline response to injury, not only essential for clot formation but also important for tissue repair. Indeed, the reparative influence of platelets has long been exploited therapeutically where application of platelet concentrates expedites wound recovery. Despite this, the mechanisms of platelet-triggered cytoprotection are poorly understood.

Oxidation of an exposed methionine instigates the aggregation of glyceraldehyde-3-phosphate dehydrogenase.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous and abundant protein that participates in cellular energy production. GAPDH normally exists in a soluble form; however, following necrosis, GAPDH and numerous other intracellular proteins convert into an insoluble disulfide-cross-linked state via the process of "nucleocytoplasmic coagulation." Here, free radical-induced aggregation of GAPDH was studied as an in vitro model of nucleocytoplasmic coagulation.

The eyes have it: the role of attention in cognitive reappraisal of social stimuli.

Cognitive reappraisal (CR) is a commonly used emotion-regulation strategy that has been shown to influence affective, cognitive, and social outcomes. Although progress has been made in elucidating the mechanisms underlying CR, the role of attention remains unclear. In the present study, we investigated the role of attention in CR by tracking participants' gazes during the presentation of videos depicting people in negative moods.