Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood

BACKGROUND: Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early-life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. OBJECTIVE: Our aim was to identify new loci interacting with ELTS exposure on time-to-asthma onset (TAO) in childhood. METHODS: We conducted genome-wide interaction analyses of ELTS exposure on time-to-asthma onset in childhood in five European-ancestry studies (totaling 8,273 subjects) using Cox proportional-hazard model. The results of all five genome-wide analyses were meta-analyzed. RESULTS: The 13q21 locus showed genome-wide significant interaction with ELTS exposure (P=4.3x10-8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P<5x10-6 ) were found at three other loci: 20p12 (rs13037508 within MACROD2; P=4.9x10-7 ), 14q22 (rs7493885 near NIN; P=2.9x10-6 ) and 2p22 (rs232542 near CYP1B1; P=4.1x10-6 ). Functional annotations and the literature showed that the lead SNPs at these four loci influence DNA methylation in the blood and are located nearby CpG sites reported to be associated with exposure to tobacco smoke components, which strongly support our findings. CONCLUSION AND CLINICAL RELEVANCE: We identified novel candidate genes interacting with ELTS exposure on time-to-asthma onset in childhood. These genes have plausible biological relevance related to tobacco smoke exposure. Further epigenetic and functional studies are needed to confirm these findings and to shed light on the underlying mechanisms. This article is protected by copyright. All rights reserved

Transport of Canadian forest fire smoke over the UK as observed by lidar

Layers of aerosol at heights between 2 and 11&thinsp;km were observed with Raman lidars in the UK between 23 and 31 May 2016. A network of these lidars, supported by ceilometer observations, is used to map the extent of the aerosol and its optical properties. Space-borne lidar profiles show that the aerosol originated from forest fires over western Canada around 17 May, and indeed the aerosol properties – weak volume depolarisation ( &lt; 5&thinsp;%) and a lidar ratio at 355&thinsp;nm in the range 35–65&thinsp;sr – were consistent with long-range transport of forest fire smoke. The event was unusual in its persistence – the smoke plume was drawn into an atmospheric block that kept it above north-western Europe for 9 days. Lidar observations show how the smoke layers became optically thinner during this period, but the lidar ratio and aerosol depolarisation showed little change. The results demonstrate the value of a dense network of observations for tracking forest fire smoke, and show how the dispersion of smoke in the free troposphere leads to the emergence of discrete thin layers in the far field. They also show how atmospheric blocking can keep a smoke plume in the same geographic area for over a week.</p

Design and Reliability Performance Evaluation of Network Coding Schemes for Lossy Wireless Networks

This thesis investigates lossy wireless networks, which are wireless communication networks consisting of lossy wireless links, where the packet transmission via a lossy wireless link is successful with a certain value of probability. In particular, this thesis analyses all-to-all broadcast in lossy wireless networks, where every node has a native packet to transmit to all other nodes in the network. A challenge of all-to-all broadcast in lossy wireless networks is the reliability, which is defined as the probability that every node in the network successfully obtains a copy of the native packets of all other nodes. In this thesis, two novel network coding schemes are proposed, which are the neighbour network coding scheme and the random neighbour network coding scheme. In the two proposed network coding schemes, a node may perform a bit-wise exclusive or (XOR) operation to combine the native packet of itself and the native packet of its neighbour, called the coding neighbour, into an XOR coded packet. The reliability of all-to-all broadcast under both the proposed network coding schemes is investigated analytically using Markov chains. It is shown that the reliability of all-to-all broadcast can be improved considerably by employing the proposed network coding schemes, compared with non-coded networks with the same link conditions, i.e. same probabilities of successful packet transmission via wireless channels. Further, the proposed schemes take the link conditions of each node into account to maximise the reliability of a given network. To be more precise, the first scheme proposes the optimal coding neighbour selection method while the second scheme introduces a tuning parameter to control the probability that a node performs network coding at each transmission. The observation that channel condition can have a significant impact on the performance of network coding schemes is expected to be applicable to other network coding schemes for lossy wireless networks

Genome-wide association and Meta-analysis of age at onset in Parkinson Disease

Background and Objectives Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Methods A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). Results The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10−8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025): (rs34311866: β(SE)COURAGE = 0.477(0.203), pCOURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE)COURAGE+IPDGC = 0.720(0.122), pCOURAGE+IPDGC = 3.13 × 10−9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = −0.526(0.096), pCOURAGE+IPDGC = 4.41 × 10−8). Discussion Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of BST1 as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Background Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. Objective We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. Methods We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. Results We confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31). Conclusions We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA

Zróżnicowanie zawartości glikozydów fenolowych i makroelementów (K, Ca, Mg) w korze wierzb zielarskich

The willows with high phenolic glycosides concentrations are used in herbal production. The knowledge about these metabolites are well documented, but less is known about macroelement concentration in the bark of herb willows. The aims of this study were to evaluate the content of phenolic glycosides and macroelements in the bark of Salix alba, S. daphnoides and S. purpurea originating from their natural habitats and cultivated on the two different soil types. The study was carried out in 2009 and 2010 on a 5–6 year-old plantation. All the species cultivated on the loess soil were characterized by the highest concentration of phenolic glycosides in the bark. The soil type under willow plantation determined both the content of phenolic glycosides and the content of macroelements in the bark of all the three willow species. Calcium primarily determined the difference in the chemical composition of the bark. Among the species studied, Salix alba was characterized by the highest content of K, Ca and Mg in the bark, compared to the other species studied, irrespective of the soil conditions.Wierzby charakteryzujące się dużą zawartością glikozydów fenolowych są wykorzystywane jako surowiec zielarski. Koncentracja tych metabolitów w korze jest stosunkowo dobrze udokumentowana, natomiast niewiele jest informacji odnośnie zawartości makroelementów. Celem badań było określenie zawartości glikozydów fenolowych oraz makroelementów (K, Ca, Mg) w korze Salix alba, S. daphnoides i S. purpurea, pozyskanych z naturalnych siedlisk występowania tych gatunków i uprawianych na różnych jednostkach glebowych. Badania były przeprowadzone w latach 2009 i 2010 na pięcioboi sześcioletniej plantacji. Wszystkie badane gatunki uprawiane na glebie lessowej charakteryzowały się większą zawartością glikozydów fenolowych w korze w porównaniu z uprawianymi na glebie piaszczystej. Właściwości gleby determinowały zarówno zawartość glikozydów fenolowych, jak i zawartość makroelementów w korze wszystkich ocenianych gatunków Salix sp. Z badanych pierwiastków zawartość wapnia w Salicis cortex była najbardziej zróżnicowana. Salix alba odznaczała się największą zawartością potasu, wapnia i magnezu w korze w porównaniu z pozostałymi gatunkami, niezależnie od warunków glebowych

Salix myrsinifolia Salisb. źródłem glikozydów fenolowych: rozmieszczenie i charakterystyka warunków siedliskowych w Polsce środkowowschodniej

In Poland, Salix myrsinifolia Salisb. reaches the south-western border of the dense geographical range. Therefore, the number of natural stands of this species is limited. The aims of this study were: to evaluate the content of phenolic glycosides in darkleaved willow bark taken from natural sites, and to investigate the habitat conditions and natural resources of this species in mid-eastern Poland. In the sites of S. myrsinifolia the annual shoots were taken, and the content of phenolic glycosides in willow bark was determined. The plant communities with the share of this species were characterised, and pH, organic matter, macro- and microelements in soils were determined. The bark of the dark-leaved willow is characterised by a very high content of phenolic glycosides and is considered to be potential natural source of salicylates. The plant communities with share of this species were formed spontaneously on highly transformed calcareous fens where peat was mined and on agriculturally developed peatlands. The number of natural stands is small, and gather from natural habitats is limited. Therefore, this species can be a good source of quality raw material during cultivating.W Polsce Salix myrsinifolia Salisb. osiąga południowo-zachodnią granicę zwartego geograficznego zasięgu, toteż liczba naturalnych stanowisk tego gatunku jest ograniczona. Celem badań było określenie zawartości glikozydów fenolowych w korze wierzby czarniawej ze stanowisk naturalnych, ocena warunków siedliskowych oraz zasobów tego gatunku w Polsce środkowo-wschodniej. W korze pobranej z jednorocznych pędów S. myrsinifolia oznaczono zawartość glikozydów fenolowych. Scharakteryzowano zbiorowiska roślinne z udziałem tego gatunku, a w pobranych próbkach glebowych oznaczono pH, materię organiczną oraz makro- i mikroelementy. Kora wierzby czarniawej charakteryzowała się bardzo wysoką zawartością glikozydów fenolowych i może być traktowana jako potencjalne źródło salicylanów. Zbiorowiska roślinne z udziałem tego gatunku wykształciły się spontanicznie na torfowiskach węglanowych przekształconych w związku z eksploatacją torfu oraz rolniczo zagospodarowanych. Liczba naturalnych stanowisk Salix myrsinifolia jest niewielka, a pozyskiwanie kory ze stanu naturalnego ograniczone. Celowe wydaje się wprowadzenie tego gatunku do uprawy

Zasoby Nuphar lutea (L.) Sibth. &amp; Sm. w Polsce środkowowschodniej jako potencjalne źródło surowca zielarskiego

The aim of this study was to characterize the phytocoenoses with a share of Nuphar lutea (L.) Sibth. & Sm. and to evaluate the area of patches of Nupharo-Nymphaeetum albae Tomaszewicz 1977 as well as resources of the yellow water lily that can be used as a source of valuable medicinal raw material. The field investigations were carried out in the summer seasons of 2009–2018, and fifty-eight lakes were included in this study. Nuphar lutea is a very interesting plant species due to considerable concentration of secondary metabolites and their biological activity. Therefore, under conditions of eastern Poland, it can be a valuable raw material for pharmaceutical purposes. The largest Nupharo-Nymphaeetum albae phytocoenoses with N. lutea as the main floristic component are localized especially in retention reservoirs connected with the Wieprz-Krzna Canal and other lakes of a natural character. They are often very shallow basins. Therefore, removal of a biomass, especially in the case of small lakes that overgrow at a very rapid rate, can significantly slow down their shallowing and they will remain and function in the landscape over a longer time. Harvesting the N. lutea leaves can decelerate the process of shallowing of water bodies, especially in the case of retention reservoirs, and may contribute to their better functioning. Collected raw material can be a source of valuable secondary metabolites suitable for the pharmaceutical industry