Brainstem and Spinal Cord Circuitry Regulating REM Sleep and Muscle Atonia

Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM) sleep.To determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuits, we injected an adeno-associated viral vector expressing Cre recombinase (AAV-Cre) into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2) or vesicular GABA-glycine transporter (VGAT) genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD) and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT) and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT-SLD, ventrolateral periaqueductal gray matter (vlPAG) and lateral pontine tegmentum (LPT) are not critically involved in REM sleep control.These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD)

ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe

The Gene Ontology knowledgebase in 2023

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project

Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer fiveoriginal research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams renderedstatistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.</div

Addressing climate change with behavioral science: a global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

The formation and fate of internal waves in the South China Sea

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 521 (2015): 65-69, doi:10.1038/nature14399.Internal gravity waves, the subsurface analogue of the familiar surface gravity waves that break on beaches, are ubiquitous in the ocean. Because of their strong vertical and horizontal currents, and the turbulent mixing caused by their breaking, they impact a panoply of ocean processes, such as the supply of nutrients for photosynthesis1, sediment and pollutant transport2 and acoustic transmission3; they also pose hazards for manmade structures in the ocean4. Generated primarily by the wind and the tides, internal waves can travel thousands of kilometres from their sources before breaking5, posing severe challenges for their observation and their inclusion in numerical climate models, which are sensitive to their effects6-7. Over a decade of studies8-11 have targeted the South China Sea, where the oceans’ most powerful internal waves are generated in the Luzon Strait and steepen dramatically as they propagate west. Confusion has persisted regarding their generation mechanism, variability and energy budget, however, due to the lack of in-situ data from the Luzon Strait, where extreme flow conditions make measurements challenging. Here we employ new observations and numerical models to (i) show that the waves begin as sinusoidal disturbances rather than from sharp hydraulic phenomena, (ii) reveal the existence of >200-m-high breaking internal waves in the generation region that give rise to turbulence levels >10,000 times that in the open ocean, (iii) determine that the Kuroshio western boundary current significantly refracts the internal wave field emanating from the Luzon Strait, and (iv) demonstrate a factor-of-two agreement between modelled and observed energy fluxes that enables the first observationally-supported energy budget of the region. Together, these findings give a cradle-to-grave picture of internal waves on a basin scale, which will support further improvements of their representation in numerical climate predictions.Our work was supported by the U.S. Office of Naval Research and the Taiwan National Science Council.2015-10-2

The formation and fate of internal waves in the South China Sea

Internal gravity waves, the subsurface analogue of the familiar surface gravity waves that break on beaches, are ubiquitous in the ocean. Because of their strong vertical and horizontal currents, and the turbulent mixing caused by their breaking, they affect a panoply of ocean processes, such as the supply of nutrients for photosynthesis¹, sediment and pollutant transport² and acoustic transmission³; they also pose hazards for man-made structures in the ocean⁴. Generated primarily by the wind and the tides, internal waves can travel thousands of kilometres from their sources before breaking⁵, making it challenging to observe them and to include them in numerical climate models, which are sensitive to their effects[superscript 6,7]. For over a decade, studies[superscript 8–11] have targeted the South China Sea, where the oceans’ most powerful known internal waves are generated in the Luzon Strait and steepen dramatically as they propagate west. Confusion has persisted regarding their mechanism of generation, variability and energy budget, however, owing to the lack of in situ data from the Luzon Strait, where extreme flow conditions make measurements difficult. Here we use new observations and numerical models to (1) show that the waves begin as sinusoidal disturbances rather than arising from sharp hydraulic phenomena, (2) reveal the existence of >200-metre-high breaking internal waves in the region of generation that give rise to turbulence levels >10,000 times that in the open ocean, (3) determine that the Kuroshio western boundary current noticeably refracts the internal wave field emanating from the Luzon Strait, and (4) demonstrate a factor-of-two agreement between modelled and observed energy fluxes, which allows us to produce an observationally supported energy budget of the region. Together, these findings give a cradle-to-grave picture of internal waves on a basin scale, which will support further improvements of their representation in numerical climate predictions