Mutations in fetal genes involved in innate immunity and host defense against microbes increase risk of preterm premature rupture of membranes (PPROM)

BackgroundTwin studies have revealed a significant contribution of the fetal genome to risk of preterm birth. Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm delivery. Infection and inflammation of the fetal membranes is commonly found associated with PPROM.MethodsWe carried out whole exome sequencing (WES) of genomic DNA from neonates born of Africanâ American mothers whose pregnancies were complicated by PPROM (76) or were normal term pregnancies (N = 43) to identify mutations in 35 candidate genes involved in innate immunity and host defenses against microbes. Targeted genotyping of mutations in the candidates discovered by WES was conducted on an additional 188 PPROM cases and 175 controls.ResultsWe identified rare heterozygous nonsense and frameshift mutations in several of the candidate genes, including CARD6, CARD8, DEFB1, FUT2, MBL2, NLP10, NLRP12, and NOD2. We discovered that some mutations (CARD6, DEFB1, FUT2, MBL2, NLRP10, NOD2) were present only in PPROM cases.ConclusionsWe conclude that rare damaging mutations in innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by PPROM. These findings suggest that the risk of preterm birth in Africanâ Americans may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products.Rare damaging mutations in fetal innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by preterm premature rupture of membranes. An increased risk of preterm birth may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140041/1/mgg3330.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140041/2/mgg3330_am.pd

A summary of pain and pain-related variables in the Avon Longitudinal Study of Parents and Children

To study pain, data on pain characteristics, possible triggers and consequences - such as the impact of pain on people's lives - need to be available. When not collated, described and/or organised in a systematic manner, it can be difficult to assess how useful an existing dataset may be for one's project. This data note describes and categorises the complex and multi-modal indices of pain available in the Avon Longitudinal Study of Parents and Children (ALSPAC). Data from two generations of the ALSPAC cohort; index child participants (Generation 1, G1), their mothers and fathers/mothers' partners (Generation 0, G0) were used. Search terms such as 'pain', 'ache', 'hurt', 'sore', specific pain conditions, labour pain and methods of pain relief were used to identify pain and pain-related variables. These data were extracted from all waves of data collection. We developed pain categories and subsequently categorised variables in an iterative process. Repeated measurements of the same variables over waves of data collection were also identified. We identified 21 categories of pain variables, which were subsequently grouped into themes: pain characteristics, extended pain characteristics and causes, treatment for pain, pain interference and pain-related to specific events. Pain and pain-related data have been collected from G1 participants, G0 mothers, and G0 partners, although there are fewer data for the partners. There were some repeated measurements, most commonly, of pain location. As is typical with longitudinal birth cohort studies, maternal proxy-reports were used during participants' younger years and self-reports were utilised from adolescence onwards. Researchers interested in studying pain can feasibly do so in two generations of a regional UK population who have been followed up over 30 years. ALSPAC can be used to study pain from the early years through to young adulthood and in mothers from the perinatal period onwards. [Abstract copyright: Copyright: © 2024 Ly A et al.

Associations of risk factors of e-cigarette and cigarette use and susceptibility to use among baseline PATH study youth participants (2013–2014)

Introduction: Improved understanding of the distribution of traditional risk factors of cigarette smoking among youth who have ever used or are susceptible to e-cigarettes and cigarettes will inform future longitudinal studies examining transitions in use. Methods: Multiple logistic regression analysis was conducted using data from youth (ages 12–17 years) who had ever heard of e-cigarettes at baseline of the PATH Study (n = 12,460) to compare the distribution of risk factors for cigarette smoking among seven mutually exclusive groups based on ever cigarette/e-cigarette use and sus- ceptibility status. Results: Compared to committed never users, youth susceptible to e-cigarettes, cigarettes, or both had increasing odds of risk factors for cigarette smoking, with those susceptible to both products at highest risk, followed by cigarettes and e-cigarettes. Compared to e-cigarette only users, dual users had higher odds of nearly all risk factors (aOR range = 1.6–6.8) and cigarette only smokers had higher odds of other (non-e-cigarette) tobacco use (aOR range=1.5–2.3), marijuana use (aOR=1.9, 95%CI=1.4–2.5), a high GAIN substance use score (aOR = 1.9, 95%CI = 1.1–3.4), low academic achievement (aOR range = 1.6–3.4), and exposure to smoking (aOR range = 1.8–2.1). No differences were observed for externalizing factors (depression, anxiety, etc.), sen- sation seeking, or household use of non-cigarette tobacco. Conclusions: Among ever cigarette and e-cigarette users, dual users had higher odds of reporting traditional risk factors for smoking, followed by single product cigarette smokers and e-cigarette users. Understanding how e- cigarette and cigarette users differ may inform youth tobacco use prevention efforts and advise future studies assessing probability of progression of cigarette and e-cigarette use

Climate change and outdoor regional living plant collections: an example from mainland Portugal

Original PaperClimate change threatens not only plant species occurring naturally, but also impacts on regional living plant collections, which play an important role in ex situ conservation strategies. In the last few years, several global circulation models have been used to predict different global climate change scenarios. Due to their coarse resolutions, and while more detailed regional approaches are not available, downscaling techniques have been proposed, as a very simple first approach to increase detail. We analysed seven sites on mainland Portugal with potential for species conservation (four botanic gardens and three universities), in the light of downscaled climate change scenarios, using an environmental envelope approach and a predefined bioclimatic neighbourhood for each site. Thresholds for the bioclimatic neighbourhood were based on Rivas-Martı´nez’s Bioclimatic Classification of the Earth. For each site, the expected geographical shift of its original bioclimatic neighbourhood (1950–2000) was mapped for 2020, 2050 and 2080. Analysing those shifts enabled us to delineate knowledge-transfer paths between sites, according to the analysed scenarios. We concluded that, according to the Intergovernmental Panel on Climate Change A2 scenario, all considered sites will be outside the predefined bioclimatic neighbourhood by 2080, while according to the B2 scenario all of them will be inside that neighbourhood, although sometimes marginally so. Therefore, the implementation of global sustainability measures as considered in the B2 scenario family can be of great importance in order to delay significantly the impacts of climate change, giving extra time for the adaptation of the outdoor regional living plant collectionsinfo:eu-repo/semantics/publishedVersio

The effects of explicit versus parameterized convection on the MJO in a large-domain high-resolution tropical case study. Part I: Characterization of large-scale organization and propagation

High-resolution simulations over a large tropical domain (∼20◦S–20◦N and 42◦E–180◦E) using both explicit and parameterized convection are analyzed and compared to observations during a 10-day case study of an active Madden-Julian Oscillation (MJO) event. The parameterized convection model simulations at both 40 km and 12 km grid spacing have a very weak MJO signal and little eastward propagation. A 4 km explicit convection simulation using Smagorinsky subgrid mixing in the vertical and horizontal dimensions exhibits the best MJO strength and propagation speed. 12 km explicit convection simulations also perform much better than the 12 km parameterized convection run, suggesting that the convection scheme, rather than horizontal resolution, is key for these MJO simulations. Interestingly, a 4 km explicit convection simulation using the conventional boundary layer scheme for vertical subgrid mixing (but still using Smagorinsky horizontal mixing) completely loses the large-scale MJO organization, showing that relatively high resolution with explicit convection does not guarantee a good MJO simulation. Models with a good MJO representation have a more realistic relationship between lower-free-tropospheric moisture and precipitation, supporting the idea that moisture-convection feedback is a key process for MJO propagation. There is also increased generation of available potential energy and conversion of that energy into kinetic energy in models with a more realistic MJO, which is related to larger zonal variance in convective heating and vertical velocity, larger zonal temperature variance around 200 hPa, and larger correlations between temperature and ascent (and between temperature and diabatic heating) between 500–400 hPa

Forcing single-column models using high-resolution model simulations

To use single column models (SCMs) as a research tool for parametrisation development and process studies, the SCM must be supplied with realistic initial profiles, forcing fields and boundary conditions. We propose a new technique for deriving these required profiles, motivated by the increase in number and scale of high-resolution convection-permitting simulations. We suggest that these high-resolution simulations be coarse-grained to the required resolution of an SCM, and thereby be used as a proxy for the ‘true’ atmosphere. This paper describes the implementation of such a technique. We test the proposed methodology using high-resolution data from the UK Met Office’s Unified Model (MetUM), with a resolution of 4 km, covering a large tropical domain. This data is coarse grained and used to drive the European Centre for Medium-Range Weather Forecast’s (ECMWF) Integrated Forecasting 26 System (IFS) SCM. The proposed method is evaluated by deriving IFS SCM forcing profiles from a consistent T639 IFS simulation. The SCM simulations track the global model, indicating a consistency between the estimated forcing fields and the ‘true’ dynamical forcing in the global model. We demonstrate the benefits of selecting SCM forcing profiles from across a large-domain, namely robust statistics, and the ability to test the SCM over a range of boundary conditions. We also compare driving the SCM with the coarse-grained datase to driving it using the ECMWF operational analysis. We conclude by highlighting the importance of understanding biases in the high-resolution dataset, and suggest that our approach be used in combination with observationally derived forcing datasets

ENM2020 : A FREE ONLINE COURSE AND SET OF RESOURCES ON MODELING SPECIES NICHES AND DISTRIBUTIONS

The field of distributional ecology has seen considerable recent attention, particularly surrounding the theory, protocols, and tools for Ecological Niche Modeling (ENM) or Species Distribution Modeling (SDM). Such analyses have grown steadily over the past two decades-including a maturation of relevant theory and key concepts-but methodological consensus has yet to be reached. In response, and following an online course taught in Spanish in 2018, we designed a comprehensive English-language course covering much of the underlying theory and methods currently applied in this broad field. Here, we summarize that course, ENM2020, and provide links by which resources produced for it can be accessed into the future. ENM2020 lasted 43 weeks, with presentations from 52 instructors, who engaged with >2500 participants globally through >14,000 hours of viewing and >90,000 views of instructional video and question-and-answer sessions. Each major topic was introduced by an "Overview" talk, followed by more detailed lectures on subtopics. The hierarchical and modular format of the course permits updates, corrections, or alternative viewpoints, and generally facilitates revision and reuse, including the use of only the Overview lectures for introductory courses. All course materials are free and openly accessible (CC-BY license) to ensure these resources remain available to all interested in distributional ecology.Peer reviewe