The orphan G protein-coupled receptor (GPCR) GPR161 plays a central role in development by suppressing Hedgehog signaling. The fundamental basis of how GPR161 is activated remains unclear. Here, we determined a cryogenic-electron microscopy structure of active human GPR161 bound to heterotrimeric G.
View Article and Find Full Text PDFThe orphan G protein-coupled receptor (GPCR) GPR161 is enriched in primary cilia, where it plays a central role in suppressing Hedgehog signaling. GPR161 mutations lead to developmental defects and cancers. The fundamental basis of how GPR161 is activated, including potential endogenous activators and pathway-relevant signal transducers, remains unclear.
View Article and Find Full Text PDFBackground: On 6 March 2020, a big fire in a village forced the firefighters to draw water simultaneously from many sources, including the Adige river. From 9 March, an increasing number of inhabitants reported gastrointestinal symptoms. We describe the outbreak and the challenges linked to the concurrent COVID-19 spread.
View Article and Find Full Text PDFMNX1 encodes a homeobox transcription factor with conserved embryonic requirements in spinal motor neuron formation and pancreatic beta-cell differentiation. Mutations in MNX1 are associated with dominantly inherited Currarino syndrome and neonatal diabetes. To better understand embryonic MNX1 functions we generated an hiPSC-1 knock-in line heterozygously expressing MNX1 C-terminally tagged with 2xTY1 together with a T2A-separated red fluorescent reporter mScarlet.
View Article and Find Full Text PDFHedgehog (Hh) ligands act as morphogens to direct patterning and proliferation during embryonic development. Protein kinase A (PKA) is a central negative regulator of Hh signalling, and in the absence of Hh ligands, PKA activity prevents inappropriate expression of Hh target genes. The orphan G-protein-coupled receptor Gpr161 contributes to the basal Hh repression machinery by activating PKA.
View Article and Find Full Text PDFBackground: Seasonal influenza vaccination (SIV) is an effective and safe way to prevent influenza. Public health institutions around the world consequently recommend SIV to certain groups at risk, including healthcare worker's (HCWs). Even if SIV is free of charge, the vaccination coverage rate remains low, however.
View Article and Find Full Text PDFPharmacologically or immunologically induced hypersensitivity to penicillin is frequent. Immunological, i.e.
View Article and Find Full Text PDFA 24-year-old woman with lymph vessel dysplasia had experienced a progressive edema of her legs since her second year of life and progressive facial edema for the past year. She also had telangiectasias and papules on the background of a diffuse erythema as well as marked seborrhea on her face. Histopathological examination of a representative facial lesion revealed a granulomatous dermatitis with periadnexal distribution mainly consisting of lymphocytes and histiocytes.
View Article and Find Full Text PDFThe recent structural and functional analysis of the high affinity receptor for IgE (Fc epsilon RI) expressed on human epidermal Langerhans cells (LC) revealed new aspects of the biology of this structure. In contrast to basophils and mast cells where this receptor seems to be expressed constitutively at a constant level, the expression of Fc epsilon RI on LC varies on the donor and the inflammatory environment of the cells and lacks the classical beta-chain. This also implies functional differences most probably related to the expression level.
View Article and Find Full Text PDFTreatment of animals with superantigens results in profound immunological changes. A major fraction of all peripheral T cells becomes activated in vivo. Subsequently, successive waves of cytokines are produced with TNF playing a central pathophysiologic role.
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