26 research outputs found

    Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation

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    Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

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    Symptoms of depersonalisation/derealisation disorder as measured by brain electrical activity: A systematic review

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    Depersonalisation/derealisation disorder (DPD) refers to frequent and persistent detachment from bodily self and disengagement from the outside world. As a dissociative disorder, DPD affects 1–2 % of the population, but takes 7–12 years on average to be accurately diagnosed. In this systematic review, we comprehensively describe research targeting the neural correlates of core DPD symptoms, covering publications between 1992 and 2020 that have used electrophysiological techniques. The aim was to investigate the diagnostic potential of these relatively inexpensive and convenient neuroimaging tools. We review the EEG power spectrum, components of the event-related potential (ERP), as well as vestibular and heartbeat evoked potentials as likely electrophysiological biomarkers to study DPD symptoms. We argue that acute anxiety- or trauma-related impairments in the integration of interoceptive and exteroceptive signals play a key role in the formation of DPD symptoms, and that future research needs analysis methods that can take this integration into account. We suggest tools for prospective studies of electrophysiological DPD biomarkers, which are urgently needed to fully develop their diagnostic potential

    Combination of searches for Higgs boson decays into a photon and a massless dark photon using pp collisions at √s = 13 TeV with the ATLAS detector

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    A combination of searches for Higgs boson decays into a visible photon and a massless dark photon (H → γγd) is presented using 139 fb−1 of proton-proton collision data at a centre-of-mass energy of √s = 13 TeV recorded by the ATLAS detector at the Large Hadron Collider. The observed (expected) 95% confidence level upper limit on the Standard Model Higgs boson decay branching ratio is determined to be B(H → γγd) < 1.3% (1.5)%. The search is also sensitive to higher-mass Higgs bosons decaying into the same final state. The observed (expected) 95% confidence level limit on the cross-section times branching ratio ranges from 16 fb (20 fb) for mH = 400 GeV to 1.0 fb (1.5 fb) for mH = 3 TeV. Results are also interpreted in the context of a minimal simplified model

    Finite element analysis of composite forming at macroscopic and mesoscopic scale

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    International audienceFinite element analyses of composite reinforcement forming are presented at macroscopic and mesoscopic scale. Simulations of 3-D interlock fabric deformations are based on a hyperelastic model. The strain energy model uses the strain invariants representative to independent deformation modes of the interlock fabric. In a second part, a simulation at mescoscale of the deformation of a textile composite reinforcement is presented. The finite element model is obtained from X-ray computed tomography of the fabric in order to be close to the real geometry. The advantage of such an approach in comparison with the use of a textile geometrical modeler is shown
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