Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.

Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4+ T cells. Memory CD4+ T cells primed in high-fat diet-fed donors preferentially migrated to non-lymphoid, inflammatory sites, independent of the metabolic status of the hosts. This was due to biased CD4+ T cell differentiation into CD44hi-CCR7lo-CD62Llo-CXCR3+-LFA1+ effector memory-like T cells upon priming in high-fat diet-fed animals. Similar phenotype was observed in obese subjects in a cohort of free-living people. This developmental bias was independent of any crosstalk between CD4+ T cells and dendritic cells and was mediated via direct exposure of CD4+ T cells to palmitate, leading to increased activation of a PI3K p110δ-Akt-dependent pathway upon priming

Zebrafish Tmem230a cooperates with the Delta/Notch signaling pathway to modulate endothelial cell number in angiogenic vessels

During embryonic development, new arteries, and veins form from preexisting vessels in response to specific angiogenic signals. Angiogenic signaling is complex since not all endothelial cells exposed to angiogenic signals respond equally. Some cells will be selected to become tip cells and acquire migration and proliferation capacity necessary for vessel growth while others, the stalk cells become trailer cells that stay connected with pre-existing vessels and act as a linkage to new forming vessels. Additionally, stalk and tip cells have the capacity to interchange their roles. Stalk and tip cellular responses are mediated in part by the interactions of components of the Delta/Notch and Vegf signaling pathways. We have identified in zebrafish, that the transmembrane protein Tmem230a is a novel regulator of angiogenesis by its capacity to regulate the number of the endothelial cells in intersegmental vessels by co-operating with the Delta/Notch signaling pathway. Modulation of Tmem230a expression by itself is sufficient to rescue improper number of endothelial cells induced by aberrant expression or inhibition of the activity of genes associated with the Dll4/Notch pathway in zebrafish. Therefore, Tmem230a may have a modulatory role in vessel-network formation and growth. As the Tmem230 sequence is conserved in human, Tmem230 may represent a promising novel target for drug discovery and for disease therapy and regenerative medicine in promoting or restricting angiogenesis

HHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development.

Formation of the lymphatic system requires the coordinated expression of several key regulators: vascular endothelial growth factor C (VEGFC), its receptor FLT4, and a key transcriptional effector, PROX1. Yet, how expression of these signaling components is regulated remains poorly understood. Here, using a combination of genetic and molecular approaches, we identify the transcription factor hematopoietically expressed homeobox (HHEX) as an upstream regulator of VEGFC, FLT4, and PROX1 during angiogenic sprouting and lymphatic formation in vertebrates. By analyzing zebrafish mutants, we found that hhex is necessary for sprouting angiogenesis from the posterior cardinal vein, a process required for lymphangiogenesis. Furthermore, studies of mammalian HHEX using tissue-specific genetic deletions in mouse and knockdowns in cultured human endothelial cells reveal its highly conserved function during vascular and lymphatic development. Our findings that HHEX is essential for the regulation of the VEGFC/FLT4/PROX1 axis provide insights into the molecular regulation of lymphangiogenesis

The effects of long-term saturated fat enriched diets on the brain lipidome

The brain is highly enriched in lipids, where they influence neurotransmission, synaptic plasticity and inflammation. Non-pathological modulation of the brain lipidome has not been previously reported and few studies have investigated the interplay between plasma lipid homeostasis relative to cerebral lipids. This study explored whether changes in plasma lipids induced by chronic consumption of a well-tolerated diet enriched in saturated fatty acids (SFA) was associated with parallel changes in cerebral lipid homeostasis. Male C57Bl/6 mice were fed regular chow or the SFA diet for six months. Plasma, hippocampus (HPF) and cerebral cortex (CTX) lipids were analysed by LC-ESI-MS/MS. A total of 348 lipid species were determined, comprising 25 lipid classes. The general abundance of HPF and CTX lipids was comparable in SFA fed mice versus controls, despite substantial differences in plasma lipid-class abundance. However, significant differences in 50 specific lipid species were identified as a consequence of SFA treatment, restricted to phosphatidylcholine (PC), phosphatidylethanolamine (PE), alkyl-PC, alkenyl-PC, alkyl-PE, alkenyl-PE, cholesterol ester (CE), diacylglycerol (DG), phosphatidylinositol (PI) and phosphatidylserine (PS) classes. Partial least squares regression of the HPF/CTX lipidome versus plasma lipidome revealed the plasma lipidome could account for a substantial proportion of variation. The findings demonstrate that cerebral abundance of specific lipid species is strongly associated with plasma lipid homeostasis

The Pierre Auger Observatory Open Data

The Pierre Auger Collaboration has embraced the concept of open access to their research data since its foundation, with the aim of giving access to the widest possible community. A gradual process of release began as early as 2007 when 1% of the cosmic-ray data was made public, along with 100% of the space-weather information. In February 2021, a portal was released containing 10% of cosmic-ray data collected from 2004 to 2018, during Phase I of the Observatory. The Portal included detailed documentation about the detection and reconstruction procedures, analysis codes that can be easily used and modified and, additionally, visualization tools. Since then the Portal has been updated and extended. In 2023, a catalog of the 100 highest-energy cosmic-ray events examined in depth has been included. A specific section dedicated to educational use has been developed with the expectation that these data will be explored by a wide and diverse community including professional and citizen-scientists, and used for educational and outreach initiatives. This paper describes the context, the spirit and the technical implementation of the release of data by the largest cosmic-ray detector ever built, and anticipates its future developments.Comment: 19 pages, 8 figure

Radio Measurements of the Depth of Air-Shower Maximum at the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA), part of the Pierre Auger Observatory, is currently the largest array of radio antenna stations deployed for the detection of cosmic rays, spanning an area of $17$ km$^2$ with 153 radio stations. It detects the radio emission of extensive air showers produced by cosmic rays in the $30-80$ MHz band. Here, we report the AERA measurements of the depth of the shower maximum ($X_\text{max}$), a probe for mass composition, at cosmic-ray energies between $10^{17.5}$ to $10^{18.8}$ eV, which show agreement with earlier measurements with the fluorescence technique at the Pierre Auger Observatory. We show advancements in the method for radio $X_\text{max}$ reconstruction by comparison to dedicated sets of CORSIKA/CoREAS air-shower simulations, including steps of reconstruction-bias identification and correction, which is of particular importance for irregular or sparse radio arrays. Using the largest set of radio air-shower measurements to date, we show the radio $X_\text{max}$ resolution as a function of energy, reaching a resolution better than $15$ g cm$^{-2}$ at the highest energies, demonstrating that radio $X_\text{max}$ measurements are competitive with the established high-precision fluorescence technique. In addition, we developed a procedure for performing an extensive data-driven study of systematic uncertainties, including the effects of acceptance bias, reconstruction bias, and the investigation of possible residual biases. These results have been cross-checked with air showers measured independently with both the radio and fluorescence techniques, a setup unique to the Pierre Auger Observatory.Comment: Submitted to Phys. Rev.

Demonstrating Agreement between Radio and Fluorescence Measurements of the Depth of Maximum of Extensive Air Showers at the Pierre Auger Observatory

We show, for the first time, radio measurements of the depth of shower maximum ($X_\text{max}$) of air showers induced by cosmic rays that are compared to measurements of the established fluorescence method at the same location. Using measurements at the Pierre Auger Observatory we show full compatibility between our radio and the previously published fluorescence data set, and between a subset of air showers observed simultaneously with both radio and fluorescence techniques, a measurement setup unique to the Pierre Auger Observatory. Furthermore, we show radio $X_\text{max}$ resolution as a function of energy and demonstrate the ability to make competitive high-resolution $X_\text{max}$ measurements with even a sparse radio array. With this, we show that the radio technique is capable of cosmic-ray mass composition studies, both at Auger and at other experiments.Comment: Submitted to Phys. Rev. Let

Ground observations of a space laser for the assessment of its in-orbit performance

The wind mission Aeolus of the European Space Agency was a groundbreaking achievement for Earth observation. Between 2018 and 2023, the space-borne lidar instrument ALADIN onboard the Aeolus satellite measured atmospheric wind profiles with global coverage which contributed to improving the accuracy of numerical weather prediction. The precision of the wind observations, however, declined over the course of the mission due to a progressive loss of the atmospheric backscatter signal. The analysis of the root cause was supported by the Pierre Auger Observatory in Argentina whose fluorescence detector registered the ultraviolet laser pulses emitted from the instrument in space, thereby offering an estimation of the laser energy at the exit of the instrument for several days in 2019, 2020 and 2021. The reconstruction of the laser beam not only allowed for an independent assessment of the Aeolus performance, but also helped to improve the accuracy in the determination of the laser beam's ground track on single pulse level. The results presented in this paper set a precedent for the monitoring of space lasers by ground-based telescopes and open new possibilities for the calibration of cosmic-ray observatories.Comment: 10 pages, 10 figure