Human inborn errors of immunity mediated by the cytokines interleukin (IL)-17A/F underlie mucocutaneous candidiasis, whereas inborn errors of interferon (IFN)-γ immunity underlie mycobacterial disease. We report the discovery of bi-allelic RORC loss-of-function mutations in seven individuals from three kindreds of different ethnic origins with both candidiasis and mycobacteriosis. The lack of functional RORγ and RORγT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORγ- and RORγT-deficient individuals also displayed an impaired IFN-γ response to Mycobacterium. This principally reflected profoundly defective IFN-γ production by circulating γδ T cells and CD4+CCR6+ CXCR3+ αβ T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORγ, or RORγT, or both.

The European Space Agency (ESA) and Roscosmos ExoMars mission will launch the “Rosalind Franklin” rover in 2022 for a landing on Mars in goals of the mission are to search for signs of past and present life on Mars, investigate the water/geochemical environment as a function of depth in the shallow subsurface, and characterize the surface environment. To meet these scientific objectives while minimizing the risk for landing, a 5-year-long landing site selection process was conducted by ESA, during which eight candidate sites were down selected to one: Oxia Planum. Oxia Planum is a 200 km-wide low-relief terrain characterized by hydrous clay-bearing bedrock units located at the southwest margin of Arabia Terra. This region exhibits Noachian-aged terrains. We show in this study that the selected landing site has recorded at least two distinct aqueous environments, both of which occurred during the Noachian: (1) a first phase that led to the deposition and alteration of ∼100 m of layered clay-rich deposits and (2) a second phase of a fluviodeltaic system that postdates the widespread clay-rich layered unit. Rounded isolated buttes that overlie the clay-bearing unit may also be related to aqueous processes. Our study also details the formation of an unaltered mafic-rich dark resistant unit likely of Amazonian age that caps the other units and possibly originated from volcanism. Oxia Planum shows evidence for intense erosion from morphology (inverted features) and crater statistics. Due to these erosional processes, two types of Noachian sedimentary rocks are currently exposed. We also expect rocks at the surface to have been exposed to cosmic bombardment only recently, minimizing organic matter damage.

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These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.

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Dark magnetic spots crossing the stellar disk lead to quasiperiodic brightness variations, which allow us to constrain stellar surface rotation and photometric activity. The current work is the second of this series, where we analyze the Kepler long-cadence data of 132,921 main-sequence F and G stars and late subgiant stars. Rotation-period candidates are obtained by combining wavelet analysis with autocorrelation function. Reliable rotation periods are then selected via a machine-learning (ML) algorithm, automatic selection, and complementary visual inspection. The ML training data set comprises 26,521 main-sequence K and M stars from Paper I. To supplement the training, we analyze in the same way as Paper I, i.e., automatic selection and visual inspection, 34,100 additional stars. We finally provide rotation periods P rot and associated photometric activity proxy S ph for 39,592 targets. Hotter stars are generally faster rotators than cooler stars. For main-sequence G stars, S ph spans a wider range of values with increasing effective temperature, while F stars tend to have smaller S ph values in comparison with cooler stars. Overall for G stars, fast rotators are photometrically more active than slow rotators, with S ph saturating at short periods. The combined outcome of the two papers accounts for average P rot and S ph values for 55,232 main-sequence and subgiant FGKM stars (out of 159,442 targets), with 24,182 new P rot detections in comparison with McQuillan et al. The upper edge of the P rot distribution is located at longer P rot than found previously.

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Multicentric carpo-tarsal osteolysis (MCTO) with or without nephropathy is a rare osteolysis disorder beginning in early childhood and involving mainly carpal and tarsal bones. Renal disease appears later in life in the majority of cases and evolves quickly to end stage renal failure. Autosomal dominant (AD) inheritance has been demonstrated, with a high frequency of sporadic cases. Recently, mutations in a highly conserved region of the MAFB gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B) have been identified in MCTO patients by exome sequencing. MafB, known as a regulator of various developmental processes, is essential for osteoclastogenesis and renal development. We report here the molecular screening of MAFB in eight MCTO patients from six families. We identified MAFB mutations in all, including three novel missense mutations clustering within the hot spot mutation region. Among the eight patients, six only presented renal disease. Our report confirms the genetic homogeneity of MCTO and provides data underlying the clinical variability of this disorder.