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The CHaracterising ExOPlanet Satellite (CHEOPS) was selected in 2012, as the first small mission in the ESA Science Programme and successfully launched in December 2019. CHEOPS is a partnership between ESA and Switzerland with important contributions by ten additional ESA Member States. CHEOPS is the first mission dedicated to search for transits of exoplanets using ultrahigh precision photometry on bright stars already known to host planets. As a follow-up mission, CHEOPS is mainly dedicated to improving, whenever possible, existing radii measurements or provide first accurate measurements for a subset of those planets for which the mass has already been estimated from ground-based spectroscopic surveys and to following phase curves. CHEOPS will provide prime targets for future spectroscopic atmospheric characterisation. Requirements on the photometric precision and stability have been derived for stars with magnitudes ranging from 6 to 12 in the V band. In particular, CHEOPS shall be able to detect Earth-size planets transiting G5 dwarf stars in the magnitude range between 6 and 9 by achieving a photometric precision of 20 ppm in 6 hours of integration. For K stars in the magnitude range between 9 and 12, CHEOPS shall be able to detect transiting Neptune-size planets achieving a photometric precision of 85 ppm in 3 hours of integration. This is achieved by using a single, frame-transfer, back-illuminated CCD detector at the focal plane assembly of a 33.5 cm diameter telescope. The 280 kg spacecraft has a pointing accuracy of about 1 arcsec rms and orbits on a sun-synchronous dusk-dawn orbit at 700 km altitude. The nominal mission lifetime is 3.5 years. During this period, 20% of the observing time is available to the community through a yearly call and a discretionary time programme managed by ESA.

FOXP3 deficiency in mice and in patients with immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome results in fatal autoimmunity by altering regulatory T (T reg ) cells. CD4 + T cells in patients with IPEX syndrome and Foxp3 -deficient mice were analyzed by single-cell cytometry and RNA-sequencing, revealing heterogeneous T reg -like cells, some very similar to normal T reg cells, others more distant. Conventional T cells showed no widespread activation or helper T cell bias, but a monomorphic disease signature affected all CD4 + T cells. This signature proved to be cell extrinsic since it was extinguished in mixed bone marrow chimeric mice and heterozygous mothers of patients with IPEX syndrome. Normal T reg cells exerted dominant suppression, quenching the disease signature and revealing in mutant T reg -like cells a small cluster of genes regulated cell-intrinsically by FOXP3, including key homeostatic regulators. We propose a two-step pathogenesis model: cell-intrinsic downregulation of core FOXP3-dependent genes destabilizes T reg cells, de-repressing systemic mediators that imprint the disease signature on all T cells, furthering T reg cell dysfunction. Accordingly, interleukin-2 treatment improved the T reg -like compartment and survival. FOXP3 deficiency leads to dramatic loss of immune homeostasis. This multicenter collaborative group finds that loss of FOXP3 function only disrupts a few core genes, but this unmasks a degree of systemic inflammation, and it is this environment that then strongly perturbs T reg cells.

This work focuses on the manufacture of core-sheath nanofibers (NFs) based on chitosan (CHT) as sheath and cyclodextrin polymer (PCD) as core and loaded with triclosan (TCL). In parallel, monolithic NFs consisting of blended CHT-PCD and TCL were prepared. Nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier Transform Infrared spectroscopy (FTIR). SEM displayed the morphology of NFs and the structure of the nanowebs, while TEM evidenced the core-sheath structure of NFs prepared by coaxial electrospinning. The core diameters and sheath thicknesses were found dependent on respective flow rates of both precursor solutions. Nanofibers stability and TCL release in aqueous medium were studied and correlated with the antibacterial activity against Staphylococcus aureus and Escherichia coli. Results showed that the release profiles of TCL and therefore the antibacterial activity were directly related to the type of nanofibers. In the case of monolithic nanofibers, the NFs matrix was composed of polyelectrolyte complex (PEC formed between CHT and PCD) and resulted in a prolonged release of TCL and a sustained antibacterial effect. In the case of core-sheath NFs, the PEC was formed only at the core-sheath interface, leading to less stable NFs and therefore to a faster release of TCL, and to a less extended antibacterial activity compared to monolithic ones.

This work focuses on the manufacture of core-sheath nanofibers (NFs) based on chitosan (CHT) as sheath and cyclodextrin polymer (PCD) as core and loaded with triclosan (TCL). In parallel, monolithic NFs consisting of blended CHT-PCD and TCL were prepared. Nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier Transform Infrared spectroscopy (FTIR). SEM displayed the morphology of NFs and the structure of the nanowebs, while TEM evidenced the core-sheath structure of NFs prepared by coaxial electrospinning. The core diameters and sheath thicknesses were found dependent on respective flow rates of both precursor solutions. Nanofibers stability and TCL release in aqueous medium were studied and correlated with the antibacterial activity against Staphylococcus aureus and Escherichia coli. Results showed that the release profiles of TCL and therefore the antibacterial activity were directly related to the type of nanofibers. In the case of monolithic nanofibers, the NFs matrix was composed of polyelectrolyte complex (PEC formed between CHT and PCD) and resulted in a prolonged release of TCL and a sustained antibacterial effect. In the case of core-sheath NFs, the PEC was formed only at the core-sheath interface, leading to less stable NFs and therefore to a faster release of TCL, and to a less extended antibacterial activity compared to monolithic ones.

Targeted therapeutics for high-risk cancers remain an unmet medical need. Here we report the results of a large-scale screen of over 11,000 molecules for their ability to inhibit the survival and growth in vitro of human leukemic cells from multiple sources including patient samples, de novo generated human leukemia models, and established human leukemic cell lines. The responses of cells from de novo models were most similar to those of patient samples, both of which showed striking differences from the cell-line responses. Analysis of differences in subtype-specific therapeutic vulnerabilities made possible by the scale of this screen enabled the identification of new specific modulators of apoptosis, while also highlighting the complex polypharmacology of anti-leukemic small molecules such as shikonin. These findings introduce a new platform for uncovering new therapeutic options for high-risk human leukemia, in addition to reinforcing the importance of the test sample choice for effective drug discovery.

FOXP3 deficiency in mice and in patients with immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome results in fatal autoimmunity by altering regulatory T (T.sub.reg) cells. CD4.sup.+ T cells in patients with IPEX syndrome and Foxp3-deficient mice were analyzed by single-cell cytometry and RNA-sequencing, revealing heterogeneous T.sub.reg-like cells, some very similar to normal T.sub.reg cells, others more distant. Conventional T cells showed no widespread activation or helper T cell bias, but a monomorphic disease signature affected all CD4.sup.+ T cells. This signature proved to be cell extrinsic since it was extinguished in mixed bone marrow chimeric mice and heterozygous mothers of patients with IPEX syndrome. Normal T.sub.reg cells exerted dominant suppression, quenching the disease signature and revealing in mutant T.sub.reg-like cells a small cluster of genes regulated cell-intrinsically by FOXP3, including key homeostatic regulators. We propose a two-step pathogenesis model: cell-intrinsic downregulation of core FOXP3-dependent genes destabilizes T.sub.reg cells, de-repressing systemic mediators that imprint the disease signature on all T cells, furthering T.sub.reg cell dysfunction. Accordingly, interleukin-2 treatment improved the T.sub.reg-like compartment and survival.

Type II collagen is a marker of articular cartilage encoded by the COL2A1 gene. The nature of the trans factors involved in the upregulation of this gene by insulin-like growth factor-I (IGF-I) remains unclear. We found that IGF-I increased type II collagen synthesis by a transcriptional control mechanism involving a 715-bp region within the COL2A1 first-intron specific enhancer. The overproduction of L-Sox5/Sox6/Sox9 and Sp1 and decoy experiments targeting these factors demonstrated their action in concert in IGF-I trans -activation. These results were supported by the data obtained in knockdown experiments in which siRNA against Sox9/Sox6 and Sp1 prevented the IGF-I-induced increase in collagen II production. Indeed, each of these trans -activators increased the expression of others. IGF-I increased the binding of Sox9 and Sp1/Sp3 to their cis elements in the enhancer, and we provide the first evidence of Sox9 interaction with the promoter by chromatin immunoprecipitation. Interactions with COL2A1 were also observed for Sp1, p300/CBP, and Tip60. Finally, a physical interaction between Sox9, p300, Sp3, and Sp1 was detected. These data demonstrate the role of Sox9, Sp1/Sp3, and euchromatin-associated factors (p300, Tip60) in the IGF-I-induced upregulation of COL2A1 , indicating possible use of this growth factor in articular cartilage engineering applications to promote repair in patients with degenerative diseases, such as osteoarthritis.

    Independently, obesity and physical activity (PA) influence cerebral structure in aging, yet their interaction has not been investigated. We examined sex differences in the relationships among PA, obesity, and cerebral structure in aging with 340 participants who completed magnetic resonance imaging (MRI) acquisition to quantify grey matter volume (GMV) and white matter volume (WMV). Height and weight were measured to calculate body mass index (BMI). A PA questionnaire was used to estimate weekly Metabolic Equivalents. The relationships between BMI, PA, and their interaction on GMV Regions of Interest (ROIs) and WMV ROIs were examined. Increased BMI was associated with higher GMV in females, an inverse U relationship was found between PA and GMV in females, and the interaction indicated that regardless of BMI greater PA was associated with enhanced GMV. Males demonstrated an inverse U shape between BMI and GMV, and in males with high PA and had normal weight demonstrated greater GMV than normal weight low PA revealed by the interaction. WMV ROIs had a linear relationship with moderate PA in females, whereas in males, increased BMI was associated with lower WMV as well as a positive relationship with moderate PA and WMV. Males and females have unique relationships among GMV, PA and BMI, suggesting sex-aggregated analyses may lead to biased or non-significant results. These results suggest higher BMI, and PA are associated with increased GMV in females, uniquely different from males, highlighting the importance of sex-disaggregated models. Future work should include other imaging parameters, such as perfusion, to identify if these differences co-occur in the same regions as GMV.

Durum wheat (Triticum turgidum L. subsp. durum) landraces represent a prominent genetic resource for Mediterranean farming systems and breeding programs. Fourteen landraces sampled in Tunisia were genotyped with 9 microsatellite markers and characterized with 15 morphological descriptors, including resistance to the fungal disease Septoria tritici blotch (STB). The genetic diversity, nearly was as important within landraces populations (45%) than between populations (54%). It was structured in seven genetic groups and was only partly explained by the variety name or the locality of origin. Populations were also greatly diversified phenotypically (Shannon-Weaver H'=0.54) with traits related to spike and awn colours being the most diversified. Resistance to STB was either qualitative in two populations or with varying degrees of quantitative resistance in the others. A Pst-Fst comparison indicate a local adaptation of the populations. Overall, the genetic structure of Tunisian durum wheat landraces revealed a complex selection trajectory and seed exchanges between farmers. Competing Interest Statement The authors have declared no competing interest.