Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease

The scurfy mutant mouse strain suffers from a fatal lymphoproliferative disease leading to early death within 3–4 wk of age. A frame-shift mutation of the forkhead box transcription factor Foxp3 has been identified as the molecular cause of this multiorgan autoimmune disease. Foxp3 is a central control element in the development and function of regulatory T cells (T reg cells), which are necessary for the maintenance of self-tolerance. However, it is unclear whether dysfunction or a lack of T reg cells is etiologically involved in scurfy pathogenesis and its human correlate, the IPEX syndrome. We describe the generation of bacterial artificial chromosome–transgenic mice termed “depletion of regulatory T cell” (DEREG) mice expressing a diphtheria toxin (DT) receptor–enhanced green fluorescent protein fusion protein under the control of the foxp3 gene locus, allowing selective and efficient depletion of Foxp3+ T reg cells by DT injection. Ablation of Foxp3+ T reg cells in newborn DEREG mice led to the development of scurfy-like symptoms with splenomegaly, lymphadenopathy, insulitis, and severe skin inflammation. Thus, these data provide experimental evidence that the absence of Foxp3+ T reg cells is indeed sufficient to induce a scurfy-like phenotype. Furthermore, DEREG mice will allow a more precise definition of the function of Foxp3+ T reg cells in immune reactions in vivo

Detection in the summer polar stratosphere of pollution plume from East Asia and North America by balloon-borne in situ CO measurements

The SPIRALE and SWIR balloon-borne instruments have been launched in the Arctic polar region (near Kiruna, Sweden, 67.9° N, 21.1° E) during summer on 7 and 24 August 2009 and on 14 August 2009, respectively. The SPIRALE instrument performed in situ measurements of several trace gases including CO and O3 between 9 and 34 km height, with very high vertical resolution (~5 m). The SWIR-balloon instrument measured total and partial column of several species including CO. The CO stratospheric profile from SPIRALE on 7 August 2009 shows some specific structures with strong abundance of CO in the low levels (potential temperatures between 320 and 380 K, i.e. 10-14 km height). These structures are not present in the CO vertical profile of SPIRALE on 24 August 2009, for which the volume mixing ratios are typical from polar latitudes (~30 ppb). CO total columns retrieved from the IASI-MetOp satellite sounder for the three dates of flights are used to understand this spatial and temporal CO variability. SPIRALE and SWIR CO partial columns between 9 and 34 km are compared, allowing us to confirm that the enhancement of CO is localised in the stratosphere. The measurements are investigated also in terms of CO:O3 correlations and with the help of several modelling approaches (trajectory calculations, potential vorticity fields, results of chemistry transport model), in order to characterize the origin of the air masses sampled. The emission sources are qualified in terms of source type (fires, urban pollution) using NH3 and CO measurements from IASI-MetOp and MODIS data on board the TERRA/AQUA satellite. The results give strong evidence that the unusual abundance of CO on 7 August is due to surface pollution plumes from East Asia and North America transported to the upper troposphere and then entering the lower stratosphere by isentropic advection. This study highlights that the composition of low polar stratosphere in summer can be affected by anthropogenic surface emissions through long range transport

Evaluating the consistency between OCO-2 and OCO-3 XCO₂ estimates derived from the NASA ACOS version 10 retrieval algorithm

Abstract. The version 10 (v10) Atmospheric Carbon Observations from Space (ACOS) Level 2 full-physics (L2FP) retrieval algorithm has been applied to multiyear records of observations from NASA's Orbiting Carbon Observatory 2 and 3 sensors (OCO-2 and OCO-3, respectively) to provide estimates of the carbon dioxide (CO2) column-averaged dry-air mole fraction (XCO2). In this study, a number of improvements to the ACOS v10 L2FP algorithm are described. The post-processing quality filtering and bias correction of the XCO2 estimates against multiple truth proxies are also discussed. The OCO v10 data volumes and XCO2 estimates from the two sensors for the time period of August 2019 through February 2022 are compared, highlighting differences in spatiotemporal sampling but demonstrating broad agreement between the two sensors where they overlap in time and space. A number of evaluation sources applied to both sensors suggest they are broadly similar in data and error characteristics. Mean OCO-3 differences relative to collocated OCO-2 data are approximately 0.2 and −0.3 ppm for land and ocean observations, respectively. Comparison of XCO2 estimates to collocated Total Carbon Column Observing Network (TCCON) measurements shows root mean squared errors (RMSEs) of approximately 0.8 and 0.9 ppm for OCO-2 and OCO-3, respectively. An evaluation against XCO2 fields derived from atmospheric inversion systems that assimilated only near-surface CO2 observations, i.e., did not assimilate satellite CO2 measurements, yielded RMSEs of 1.0 and 1.1 ppm for OCO-2 and OCO-3, respectively. Evaluation of uncertainties in XCO2 over small areas, as well as XCO2 biases across land–ocean crossings, also indicates similar behavior in the error characteristics of both sensors. Taken together, these results demonstrate a broad consistency of OCO-2 and OCO-3 XCO2 measurements, suggesting they may be used together for scientific analyses

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing