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The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins

Eukaryotic cells have evolved quality control mechanisms to degrade aberrant mRNA molecules and prevent the synthesis of defective proteins that could be deleterious for the cell. The exosome, a protein complex with ribonuclease activity, is a key player in quality control. An early quality checkpoint takes place cotranscriptionally but little is known about the molecular mechanisms by which the e

Evolution of chain migration in an aerial insectivorous bird, the common swift Apus apus

Spectacular long-distance migration has evolved repeatedly in animals enabling exploration of resources separated in time and space. In birds, these patterns are largely driven by seasonality, cost of migration, and asymmetries in competition leading most often to leapfrog migration, where northern breeding populations winter furthest to the south. Here, we show that the highly aerial common swift

A European industrial development policy for prosperity and zero emissions

The objective of this paper is to outline and discuss the key elements of an EU industrial development policy consistent with the Paris Agreement. We also assess the current EU Industrial Strategy proposal against these elements. The “well below 2 °C” target sets a clear limit for future global greenhouse gas emissions and thus strict boundaries for the development of future material demand, indus

Clarification of the risk for venous thrombosis associated with hereditary protein S deficiency by investigation of a large kindred with a characterized gene defect

BACKGROUND: Protein S is an important regulatory protein of the coagulation cascade. The risk for venous thrombosis associated with protein S deficiency has been uncertain because all previous risk estimates used phenotypic evaluation alone, which can be ambiguous.OBJECTIVE: To quantitate the risk for thrombosis associated with a characterized protein S gene mutation that causes a Gly295-->Val sub

4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer

Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity

The GALAH survey : Unresolved triple Sun-like stars discovered by the Gaia mission

The latest Gaia data release enables us to accurately identify stars that are more luminous than would be expected on the basis of their spectral type and distance. During an investigation of the 329 best solar twin candidates uncovered among the spectra acquired by the GALAH survey, we identified 64 such overluminous stars. In order to investigate their exact composition, we developed a data-driv

Inhibition of pro-inflammatory myeloid cell responses by short-term S100A9 blockade improves cardiac function after myocardial infarction

AIMS: Neutrophils have both detrimental and beneficial effects in myocardial infarction (MI), but little is known about the underlying pathways. S100A8/A9 is a pro-inflammatory alarmin abundantly expressed in neutrophils that is rapidly released in the myocardium and circulation after myocardial ischaemia. We investigated the role of S100A8/A9 in the innate immune response to MI. METHODS AND RESUL

MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset

Macrophages contribute in the initiation and progression of insulitis during type 1 diabetes (T1D). However, the mechanisms governing their recruitment into the islets as well as the manner of retention and activation are incompletely understood. Here, we investigated a role for macrophage migration inhibitory factor (MIF) and its transmembrane receptor, CD74, in the progression of T1D. Our data i

Costs of Care of Agitation Associated With Dementia in 8 European Countries : Results From the RightTimePlaceCare Study

Objective To estimate the additional societal costs for people living with dementia (PwD) with agitation in home care (HC) and institutional long-term care (ILTC) settings in 8 European countries. Design Cross-sectional data from the RightTimePlaceCare cohort. Setting HC and ILTC settings from 8 European countries (Estonia, Finland, France, Germany, Netherlands, Spain, Sweden, and England). Partic

A post hoc study on gene panel analysis for the diagnosis of dystonia

Background: Genetic disorders causing dystonia show great heterogeneity. Recent studies have suggested that next-generation sequencing techniques such as gene panel analysis can be effective in diagnosing heterogeneous conditions. The objective of this study was to investigate whether dystonia patients with a suspected genetic cause could benefit from the use of gene panel analysis. Methods: In th

Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma

The N-methyl-d-aspartate receptor (NMDAR) coagonists glycine, d-serine and l-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general populati

Extracellular lipid loading augments hypoxic paracrine signaling and promotes glioma angiogenesis and macrophage infiltration

BackgroundPrimary brain tumors, in particular glioblastoma (GBM), remain among the most challenging cancers. Like most malignant tumors, GBM is characterized by hypoxic stress that triggers paracrine, adaptive responses, such as angiogenesis and macrophage recruitment, rescuing cancer cells from metabolic catastrophe and conventional oncological treatments. The unmet need of strategies to efficien

A new food-composition database for 437 polyphenols in 19,899 raw and prepared foods used to estimate polyphenol intakes in adults from 10 European countries

Background: Accurate assessment of polyphenol intakes is needed in epidemiologic research in order to study their health effects, and this can be particularly challenging in international study settings. Objective: The purpose of this work is to describe the procedures to prepare a comprehensive polyphenol food-composition database that was used to calculate standardized polyphenol intakes from 24

Early diagnosis of primary Sjögren's syndrome: EULAR-SS task force clinical recommendations.

Sjögren's syndrome (SjS) is a systemic autoimmune disease that mainly affects the exocrine glands, leading to generalized mucosal dryness. However, primary SjS may initially present with non-sicca (systemic) manifestations. When these features appear before the onset of an overt sicca syndrome, we may talk of an underlying 'occult' SjS. The European League Against Rheumatism (EULAR) has promoted a

GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis.

Glucagon secretion is inhibited by glucagon-like peptide-1 (GLP-1) and stimulated by adrenaline. These opposing effects on glucagon secretion are mimicked by low (1-10 nM) and high (10 muM) concentrations of forskolin, respectively. The expression of GLP-1 receptors in alpha cells is <0.2% of that in beta cells. The GLP-1-induced suppression of glucagon secretion is PKA dependent, is glucose indep

Stratospheric ozone depletion: High arctic tundra plant growth on Svalbard is not affected by enhanced UV-B after 7 years of UV-B supplementation in the field

The response of tundra plants to enhanced UV-B radiation simulating 15 and 30% ozone depletion was studied at two high arctic sites (Isdammen and Adventdalen, 78 degrees N, Svalbard).The set-up of the UV-B supplementation systems is described, consisting of large and small UV lamp arrays, installed in 1996 and 2002. After 7 years of exposure to enhanced UV-B radiation, plant cover, density, morpho

Screening and Prostate-Cancer Mortality in a Randomized European Study

Background The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer. Methods We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned

Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.

Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung

Second-generation colon capsule endoscopy compared with colonoscopy

Background: Colon capsule endoscopy (CCE) represents a noninvasive technology that allows visualization of the colon without requiring sedation and air insufflation. A second-generation colon capsule endoscopy system (PillCam Colon 2) (CCE-2) was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. Objective: To assess the feasibility, accurac

Artefactual Intelligence: The Development and Use of Cognitively Congenial Artefacts

How can tools help structure tasks to make them cognitively easier to perform? How do artefacts, and our strategies for using them, develop over time in cognitively beneficial ways? These are two of the main questions that are explored in the five papers collected in this thesis. The first paper details an ethnographic study conducted on people cooking in their homes. The study is a first pass ov