Search

Abstract Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth and function throughout life, ensuring the continuous supply of nutrients and oxygen. This involves crucial events during pre- and postnatal stages through key pathways, including vascular endothelial growth factor (VEGF) and Wnt signaling. These pathways are pivotal for brain vascular growth, expansion, and blood–brain barrier (BBB) maturation. Interestingly, during fetal and neonatal life, cerebrovascular formation coincides with the early peak activity of the hypothalamic-pituitary-gonadal axis, supporting the idea of sex hormonal influence on cerebrovascular development and barriergenesis. Sex hormonal dysregulation in early development has been implicated in neurodevelopmental disorders with highly sexually dimorphic features, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Both disorders show higher prevalence in men, with varying symptoms between sexes, with boys exhibiting more externalizing behaviors, such as aggressivity or hyperactivity, and girls displaying higher internalizing behaviors, including anxiety, depression, or attention disorders. Indeed, ASD and ADHD are linked to high prenatal testosterone exposure and reduced aromatase expression, potentially explaining sex differences in prevalence and symptomatology. In line with this, high estrogen levels seem to attenuate ADHD symptoms. At the cerebrovascular level, sex- and region-specific variations of cerebral blood flow perfusion have been reported in both conditions, indicating an impact of gonadal hormones on the brain vascular system, disrupting its ability to respond to neuronal demands. This review aims to provide an overview of the existing knowledge concerning the impact of sex hormones on cerebrovascular formation and maturation, as well as the onset of neurodevelopmental disorders. Here, we explore the concept of gonadal hormone interactions with brain vascular and BBB development to function, with a particular focus on the modulation of VEGF and Wnt signaling. We outline how these pathways may be involved in the underpinnings of ASD and ADHD. Outstanding questions and potential avenues for future research are highlighted, as uncovering sex-specific physiological and pathological aspects of brain vascular development might lead to innovative therapeutic approaches in the context of ASD, ADHD and beyond.

How do voters respond to a co-partisan political candidate after hearing about a serious scandal? We apply qualitative content analysis to open-ended text responses collected from survey respondents, focusing on 159 respondents who remain willing to vote for a hypothetical male candidate after learning that allegations of sexual harassment against him were settled out of court. We uncover two main strategies by which respondents explained and justified their willingness to look past the misconduct allegations. The dominant strategy was to extend moral licence to the candidate based on his prior good deeds; a second prominent strategy was to disbelieve and reject the allegations. Our findings offer new insights on why some political candidates and careers appear untroubled by even serious allegations of misconduct, and frames new research avenues on which voters might be more likely to extend moral licence and in what circumstances.

Abstract The Minamata Convention, a global and legally binding treaty that entered into force in 2017, aims to protect human health and the environment from harmful mercury (Hg) effects by reducing anthropogenic Hg emissions and environmental levels. The Conference of the Parties is to periodically evaluate the Convention’s effectiveness, starting in 2023, using existing monitoring data and observed trends. Monitoring atmospheric Hg levels has been proposed as a key indicator. However, data gaps exist, especially in the Southern Hemisphere. Here, we present over a decade of atmospheric Hg monitoring data at Amsterdam Island (37.80°S, 77.55°E), in the remote southern Indian Ocean. Datasets include gaseous elemental and oxidised Hg species ambient air concentrations from either active/continuous or passive/discrete acquisition methods, and annual total Hg wet deposition fluxes. These datasets are made available to the community to support policy-making and further scientific advancements.

In previous studies, the mean geothermal gradient of the Tlemcen region has been estimated as low (3.7°C/100m). The existing boreholes in the Remchi plain (North of the Tlemcen Mountains) reveal thermal waters (26-48°C) and a remarkable artesianism. To understand the hydrodynamics and origin of thermalism of this groundwater, we merged geophysical and physical-chemical data. Geophysical data allowed us to improve the resolution of the fault network, to estimate the thickness of various sandstone beds connected with the thermal reservoir and to delimit the productive aquifer. Chemical characteristics of waters have been used for a statistical analysis, which displayed two independent water clusters resulting from two hydrodynamic patterns throughout the aquifer. The hydrothermal analysis identifies the depth reached by water and the relationship between water circulation and the fault network. Comparison with previous studies allowed us to build a schematic geological model, which explains hydrodynamics, origin and role of this structure in the groundwater flow.

Objectives: The aim of this study was to demonstrate the performance and added value of rapid glucose determination in cerebrospinal fluid using a connected glucometer. Design and Methods: Intra-assay and inter-assay accuracies were calculated using residual clinical samples. Accuracies were measured by comparing the results obtained with the glucometer to those from the central laboratory on a large routine chemistry platform. Results: The intra-assay coefficients of variation were between 6.1% and 6.2% for low values (18 mg/dL) and between 5.6% and 6.8% for high values (58 mg/dL). The inter-assay coefficients of variation were between 9.4% and 16.3% for the low values (18 mg/dL) and between 5.7% and 8.7% for the high values (pool; ±75 mg/dL). The regression equation by comparison to the central laboratory was y = 4.08 + 0.82 x, with a coefficient of determination (r2) of 0.95. Conclusions: The measurement of glycorrhachia with a connected glucometer before the analysis in the central laboratory allows a rapid orientation in the deferential diagnosis of a meningitis of viral vs bacterial origin. The response time is fast (6 s) and requires only a small amount of fluid (1.2 μL), which is important in infants, especially since lumbar puncture is an integral part of the investigation of the origin of a fever in this population.

Abstract Quinones are electrochemical probes which are used for a large range of applications including bioenergetics. One electrochemical feature of quinones is their possible slow electron transfer kinetics. In this article we compared several quinones towards electron transfer kinetics and the ability of anodic pretreatment to increase electron transfer rate constant. Rotating disk electrode and chronoamperometry measurements were used to revisit their electrochemical behavior. Additionally, the number of electrons exchanged as a function of the characteristic time was used as a proxy to investigate kinetic limitations. A model was suggested to rationalize our results. Beyond a classification of quinones regarding the kinetic and thermodynamic ability of the hydroquinone form to be re‐oxidized, some intrinsic physicochemical properties were identified from our model (such as a time dependency of the exchanged number of electrons) to characterize such important redox mediators.

Abstract The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species prediction and identification of acquired resistance genes.

Lentiviral vectors (LVVs) play a critical role in gene delivery for ex vivo gene-modified cell therapies. However, the lack of scalable LVV production methods and the high cost associated with them may limit their use. In this work, we demonstrate the optimization and development of a scalable, chemically defined, animal component-free LVV production process using adherent human embryonic kidney 293T cells in a fixed-bed bioreactor. The initial studies focused on the optimization of the culture process in 2D static cultures. Process changes such as decreasing cell seeding density on day 0 from 2.5 × 104 to 5 × 103 cells/cm2, delaying the transient transfection from 24 to 120 h post-seeding, reducing plasmid DNA to 167 ng/cm2, and adding 5 mM sodium butyrate 6 h post-transfection improved functional LVV titers by 26.9-fold. The optimized animal component-free production process was then transferred to the iCELLis Nano bioreactor, a fixed-bed bioreactor, where titers of 1.2 × 106 TU/cm2 were achieved when it was operated in perfusion. In this work, comparable functional LVV titers were obtained with FreeStyle 293 Expression medium and the conventional Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum both at small and large scale.

In recent years, the global economy has been hit by a sequence of severe shocks that affected the two largest economies, the USA and the Euro Area, severely. Uncertainties about the future abound. While the challenges are similar for both economies and the policy tools resemble each other, they apply to different economic landscapes. What can they learn from each other? This paper looks at the basic structural facts, the nature of uncertainty shocks, and the efficiency of policy tools in the two economies. The key to understanding recent developments is uncertainty. This paper argues that the channel through which uncertainty influences inflation, wage cost, and unemployment is the markup firms charge to cover their cost of capital. While the measurements of uncertainty are uncertain, adding a proxy for uncertainty can improve the estimates of the basic New Keynesian model. The Federal Reserve Bank has been more successful because it operates in a more integrated capital market. In the Euro Area, uncertainty is higher than in the US and this could make disinflation in Europe more painful in terms of unemployment.

Background/Objectives: BRCA1, BRCA2, ATM, and CHEK2 are known cancer predisposition genes (CPGs), but tumor risk in patients with simultaneous pathogenic variants (PVs) in CPGs remains largely unknown. In this study, we describe six patients from five families with multiple cancers who coinherited a combination of PVs in these genes. Methods: PVs were identified using NGS DNA sequencing and were confirmed by Sanger. Results: Families 1, 2, and 3 presented PVs in BRCA2 and ATM, family 4 in BRCA2 and BRCA1, and family 5 in BRCA2 and CHEK2. PVs were identified using NGS DNA sequencing and were confirmed by Sanger. The first family included patients with kidney, prostate, and breast cancer, in addition to pancreatic adenocarcinomas. In the second family, a female had breast cancer, while a male from the third family had prostate, gastric, and pancreatic cancer. The fourth family included a male with pancreatic cancer, and the fifth family a female with breast cancer. Conclusions: The early age of diagnosis and the development of multiple cancers in the reported patients indicate a very high risk of cancer in double-heterozygous patients associated with PVs in HR-related CPGs. Therefore, in families with patients who differ from other family members in terms of phenotype, age of diagnosis, or type of cancer, the cascade testing needs to include the study of other CPGs.

The emerging heteropathotype shigatoxigenic (STEC) and extra-intestinal pathogenic Escherichia coli (ExPEC) O80:H2 has been the second leading cause of pediatric HUS in France since the mid-2010s. In contrast with other highly pathogenic STEC serotypes, for which ruminants have clearly been identified as the main human infection source, this heteropathotype’s reservoir remains unknown. In this context, we describe for the first time the isolation of seven STEC O80:H2 strains from healthy cattle on a single cattle farm in France. This study aimed at (i) characterizing the genome and (ii) investigating the phylogenetic positions of these O80:H2 STEC strains. The virulomes, resistomes, and phylogenetic positions of the seven bovine isolates were investigated using in silico typing tools, antimicrobial susceptibility testing and cgMLST analysis after short-read whole genome sequencing (WGS). One representative isolate (A13P112V1) was also subjected to long-read sequencing. The seven isolates possessed ExPEC-related virulence genes on a pR444_A-like mosaic plasmid, previously described in strain RDEx444 and known to confer multi-drug resistance. All isolates were clonally related and clustered with human clinical strains from France and Switzerland with a range of locus differences of only one to five. In conclusion, our findings suggest that healthy cattle in France could potentially act as a reservoir of the STEC-ExPEC O80:H2 pathotype.