European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.</p

Determination of the spatial frequencies caused by segmented cortical surfaces with spherical harmonic functions

In 2006 Ramon, Freeman, Haueisen und Schimpf made the case that the spatial structure of the cortex possibly influences the measurable EEG. To prove this thesis they’ve compared the power spectral density (PSD) of the spatial course of the cortex with the PSD of the simulated EEG. The thesis could be proven for the one-dimensional case by analyzing one MRT-Slice of one subject. As suboperation to prove the thesis for the more common two-dimensional case, the spectra of the spatial structure of segmented cortical surfaces were determined in this work using spherical harmonic functions (SHF), which are defined on the surface of a sphere. To do frequency analysis this way, the cortical surfaces need to be transformed to the surface of a sphere.To do so, two different methods were investigated. The first one is the Direct Sphere Projection (DSP), which just projects the outer surface of the cortex radially to the surface of the sphere. Hidden parts of the cortex become lost here. Furthermore there is no active prevention of the occurring length distortion. Therefore the DSP turned out to be unsuitable as projection method. The second investigated method was an inflation process similar to the bloating of a balloon, which was done using the software FreeSurfer. During this inflation process the original distance of the points on the cortical surfaces are actively tried to be kept. Because of the almost isometric mapping (average error 19.4% ± 0.67%) it is possible to do a correct interpretation of the determined spectra. It could be determined that the relevant frequencies are below 128 oscillations on the surface of the sphere. The 99.7%-limit (3-Sigma) of the total power is normally reached some degrees before this point. In the frequency range which was expected (8 – 30 oscillations) coves and peaks could be found in the angular power density, which can be attributed to the presence of the gyri and sulci. Therefore these wide structures could be found in the frequency spectra. The analyses were applied to 15 subjects of different age and gender.Ramon, Freeman, Haueisen und Schimpf stellten 2006 die These auf, dass die räumliche Struktur des Kortex die Möglichkeit besitzt das EEG zu beeinflussen. Zum Nachweis dieser These verglichen sie das Leistungsdichtespektrum des räumlichen Verlaufs des Kortex‘ mit dem des simulierten EEGs. Die These konnte für den eindimensionalen Fall bestätigt werden, indem ein MRT-Slice eines Probanden für die Untersuchung verwendet wurde. Als Teilarbeit zum Nachweis für den allgemeineren zweidimensionalen Fall, wurden in dieser Arbeit die Spektren der Struktur von segmentierten kortikalen Oberflächen mit Hilfe von sphärischen harmonischen Funktionen (SHF) ermittelt, welche auf der Kugeloberfläche definiert sind. Um auf diese Art eine Frequenzanalyse durchführen zu können, müssen die kortikalen Oberflächen zunächst in die Kugeldomäne überführt werden. Hierzu wurden zwei verschiedene Verfahren untersucht. Das erste Verfahren ist die Direkte Kugelprojektion (DKP), welches nur die äußere Oberfläche des Kortex radial auf die Kugeloberfläche abbildet. Verdeckte Anteile des Kortex gehen hierbei verloren. Weiterhin findet keine aktive Vermeidung der auftretenden Längenverzerrungen statt. Aus diesem Grund hat sich die DKP als unzureichendes Abbildungsverfahren herausgestellt. Das zweite untersuchte Verfahren, ist ein Aufblähungsprozess ähnlich dem Aufblasen eines Luftballons, welches mit Hilfe der Software FreeSurfer durchgeführt wurde. Hierbei wird aktiv versucht, die ursprünglichen Abstände der Punkte auf den kortikalen Oberflächen von ihren Nachbarn während des Aufblasens zu einer Kugeloberfläche beizubehalten. Aufgrund der annähernd längentreuen Abbildung (durchschnittlicher Fehler 19,4% ± 0,67%) kann somit eine korrekte Interpretation der ermittelten Spektren stattfinden. Ermittelt werden konnte, dass die relevanten Frequenzanteile unterhalb von 128 Schwingungen auf der Kugeloberfläche liegen. Die 99,7%-Grenze (3-Sigma) der Gesamtleistung wird i.d.R. schon einige Grade vorher erreicht. Im zu erwartenden Frequenzbereich (8 – 30 Schwingungen), treten Wölbungen und Peaks in den angularen Leistungsdichten auf, welche auf die Anwesenheit der Gyri und Sulci zurückzuführen sind. Somit konnten diese großen Strukturen im Frequenzspektrum wiedergefunden werden. Die Analysen wurden auf die MRT-Datensätze von 15 Probanden unterschiedlichen Alters und Geschlechts angewendet.Ilmenau, Techn. Univ., Diplomarbeit, 200

Environmental effects of stratospheric ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2019

This assessment, by the United Nations Environment Programme (UNEP) Environmental Effects Assessment Panel (EEAP), one of three Panels informing the Parties to the Montreal Protocol, provides an update, since our previous extensive assessment (Photochem. Photobiol. Sci., 2019, 18, 595–828), of recent findings of current and projected interactive environmental effects of ultraviolet (UV) radiation, stratospheric ozone, and climate change. These effects include those on human health, air quality, terrestrial and aquatic ecosystems, biogeochemical cycles, and materials used in construction and other services. The present update evaluates further evidence of the consequences of human activity on climate change that are altering the exposure of organisms and ecosystems to UV radiation. This in turn reveals the interactive effects of many climate change factors with UV radiation that have implications for the atmosphere, feedbacks, contaminant fate and transport, organismal responses, and many outdoor materials including plastics, wood, and fabrics. The universal ratification of the Montreal Protocol, signed by 197 countries, has led to the regulation and phase-out of chemicals that deplete the stratospheric ozone layer. Although this treaty has had unprecedented success in protecting the ozone layer, and hence all life on Earth from damaging UV radiation, it is also making a substantial contribution to reducing climate warming because many of the chemicals under this treaty are greenhouse gases

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020

This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive assessment (Photochemical and Photobiological Sciences, 2019, 18, 595–828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.ISSN:1474-905XISSN:1474-909