111 research outputs found
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 km with 153
radio stations. It detects the radio emission of extensive air showers produced
by cosmic rays in the MHz band. Here, we report the AERA measurements
of the depth of the shower maximum (), a probe for mass
composition, at cosmic-ray energies between to eV,
which show agreement with earlier measurements with the fluorescence technique
at the Pierre Auger Observatory. We show advancements in the method for radio
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 resolution as a function of energy, reaching a
resolution better than g cm at the highest energies, demonstrating
that radio 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 () 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 resolution as a
function of energy and demonstrate the ability to make competitive
high-resolution 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
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