Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates

Some but not all neonates are affected by prenatal exposure to serotonin reuptake inhibitor antidepressants (SRI) and maternal mood disturbances. Distinguishing the impact of these 2 exposures is challenging and raises critical questions about whether pharmacological, genetic, or epigenetic factors can explain the spectrum of reported outcomes. Using unbiased DNA methylation array measurements followed by a detailed candidate gene approach, we examined whether prenatal SRI exposure was associated with neonatal DNA methylation changes and whether such changes were associated with differences in birth outcomes. Prenatal SRI exposure was first associated with increased DNA methylation status primarily at CYP2E1(βNon-exposed = 0.06, βSRI-exposed = 0.30, FDR = 0); however, this finding could not be distinguished from the potential impact of prenatal maternal depressed mood. Then, using pyrosequencing of CYP2E1 regulatory regions in an expanded cohort, higher DNA methylation status both the mean across 16 CpG sites (P < 0.01) and at each specific CpG site (P < 0.05) was associated with exposure to lower 3rd trimester maternal depressed mood symptoms only in the SRI-exposed neonates, indicating a maternal mood x SRI exposure interaction. In addition, higher DNA methylation levels at CpG2 (P = 0.04), CpG9 (P = 0.04) and CpG10 (P = 0.02), in the interrogated CYP2E1 region, were associated with increased birth weight independently of prenatal maternal mood, SRI drug exposure, or gestational age at birth. Prenatal SRI antidepressant exposure and maternal depressed mood were associated with altered neonatal CYP2E1 DNA methylation status, which, in turn, appeared to be associated with birth weight

A Survey of Volunteered Open Geo-Knowledge Bases in the Semantic Web

Over the past decade, rapid advances in web technologies, coupled with innovative models of spatial data collection and consumption, have generated a robust growth in geo-referenced information, resulting in spatial information overload. Increasing 'geographic intelligence' in traditional text-based information retrieval has become a prominent approach to respond to this issue and to fulfill users' spatial information needs. Numerous efforts in the Semantic Geospatial Web, Volunteered Geographic Information (VGI), and the Linking Open Data initiative have converged in a constellation of open knowledge bases, freely available online. In this article, we survey these open knowledge bases, focusing on their geospatial dimension. Particular attention is devoted to the crucial issue of the quality of geo-knowledge bases, as well as of crowdsourced data. A new knowledge base, the OpenStreetMap Semantic Network, is outlined as our contribution to this area. Research directions in information integration and Geographic Information Retrieval (GIR) are then reviewed, with a critical discussion of their current limitations and future prospects

The extracellular juncture domains in the intimin passenger adopt a constitutively extended conformation inducing restraints to its sphere of action

Enterohemorrhagic and enteropathogenic Escherichia coli are among the most important food-borne pathogens, posing a global health threat of bloody diarrhea and hemolytic uremic syndrome outbreaks. The virulence factor intimin is essential for attachment and internalization into the host cells of a broad range of effacing pathogens. Intimin is translocated to the bacterial outer membrane and includes an extracellular passenger, which consists of four bacterial immunoglobulin (Big) like domains, D00-D2, extending into the fifth subdomain, a C-terminal lectin domain (D3) that binds to the Tir-receptor on the host cell. Here, we present the crystal structures of D00-D0 at 1.5 Å and D0-D1 at 1.8 Å resolution that confirm that the passenger of intimin has five distinct domains. SAXS and MD simulations show that the connector region between D00-D0 has a higher degree of rigidity and D00 likely functions as a juncture domain at the outer membrane-extracellular medium interface. We describe D00 as a Big domain with a specific topology found in the equivalent position in a broad range of other inverse autotransporters, including the structurally uncharacterized D0 domain in invasin. The accumulated data allows us to model the complete passenger of intimin and propose functionality to the Big domains, D00-D0-D1, extending directly from the membrane

Two-stage laser-driven plasma acceleration with external injection for EuPRAXIA

The EuPRAXIA (European Particle Research Accelerator with excellence In Applications) project aims at producing a conceptual design for the worldwide plasma-based accelerator facility, capable of delivering multi-GeV electron beams with high quality. This accelerator facility will be used for various user applications such as compact X-ray sources for medical imaging and high-energy physics detector tests. EuPRAXIA explores different approaches to plasma acceleration techniques. Laser-driven plasma wakefield acceleration with external injection of an RF-generated electron beam is one of the basic research directions of EuPRAXIA. We present studies of electron beam acceleration to GeV energies by a two-stage laser wakefield acceleration with external injection from an RF accelerator. Electron beam injection, acceleration and extraction from the plasma, using particle-in-cell simulations, are investigated

Eupraxia, a step toward a plasma-wakefield based accelerator with high beam quality

The EuPRAXIA project aims at designing the world's first accelerator based on advanced plasma-wakefield techniques to deliver 5 GeV electron beams that simultaneously have high charge, low emittance and low energy spread, which are required for applications by future user communities. Meeting this challenging objective will only be possible through dedicated effort. Many injection/acceleration schemes and techniques have been explored by means of thorough simulations in more than ten European research institutes. This enables selection of the most appropriate methods for solving each particular problem. The specific challenge of generating, extracting and transporting high charge beams, while maintaining the high quality needed for user applications, are being tackled using innovative approaches. This article highlights preliminary results obtained by the EuPRAXIA collaboration, which also exhibit the required laser and plasma parameters

Status of the Horizon 2020 EuPRAXIA conceptual design study

The Horizon 2020 project EuPRAXIA (European Plasma Research Accelerator with eXcellence In Applications) is producing a conceptual design report for a highly compact and cost-effective European facility with multi-GeV electron beams accelerated using plasmas. EuPRAXIA will be set up as a distributed Open Innovation platform with two construction sites, one with a focus on beam-driven plasma acceleration (PWFA) and another site with a focus on laser-driven plasma acceleration (LWFA). User areas at both sites will provide access to free-electron laser pilot experiments, positron generation and acceleration, compact radiation sources, and test beams for high-energy physics detector development. Support centres in four different countries will complement the pan-European implementation of this infrastructure

Status of the Horizon 2020 EuPRAXIA conceptual design study

The Horizon 2020 project EuPRAXIA (European Plasma Research Accelerator with eXcellence In Applications) is producing a conceptual design report for a highly compact and cost-effective European facility with multi-GeV electron beams accelerated using plasmas. EuPRAXIA will be set up as a distributed Open Innovation platform with two construction sites, one with a focus on beam-driven plasma acceleration (PWFA) and another site with a focus on laser-driven plasma acceleration (LWFA). User areas at both sites will provide access to free-electron laser pilot experiments, positron generation and acceleration, compact radiation sources, and test beams for high-energy physics detector development. Support centres in four different countries will complement the pan-European implementation of this infrastructure

EuPRAXIA - A compact, cost-efficient particle and radiation source

Plasma accelerators present one of the most suitable candidates for the development of more compact particle acceleration technologies, yet they still lag behind radiofrequency (RF)-based devices when it comes to beam quality, control, stability and power efficiency. The Horizon 2020-funded project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") aims to overcome the first three of these hurdles by developing a conceptual design for a first international user facility based on plasma acceleration. In this paper we report on the main features, simulation studies and potential applications of this future research infrastructure

Erratum to: EuPRAXIA Conceptual Design Report – Eur. Phys. J. Special Topics 229, 3675-4284 (2020), https://doi.org/10.1140/epjst/e2020-000127-8

International audienceThe online version of the original article can be found at http://https://doi.org/10.1140/epjst/e2020-000127-8</A