Suchergebnisse

Orexins (also called hypocretins) are hypothalamic neuropeptides that carry out essential functions in the central nervous system; however, little is known about their release and range of action in vivo owing to the limited resolution of current detection technologies. Here we developed a genetically encoded orexin sensor (OxLight1) based on the engineering of circularly permutated green fluorescent protein into the human type-2 orexin receptor. In mice OxLight1 detects optogenetically evoked release of endogenous orexins in vivo with high sensitivity. Photometry recordings of OxLight1 in mice show rapid orexin release associated with spontaneous running behavior, acute stress and sleep-to-wake transitions in different brain areas. Moreover, two-photon imaging of OxLight1 reveals orexin release in layer 2/3 of the mouse somatosensory cortex during emergence from anesthesia. Thus, OxLight1 enables sensitive and direct optical detection of orexin neuropeptides with high spatiotemporal resolution in living animals. ; The results are part of a project that has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 891959; to T.P.). We also acknowledge funding from the University of Zurich and the Swiss National Science Foundation (grant no. 310030_196455; to T.P.); Forschungskredit Candoc (to X.Z.); ETH Zurich (to D.B.); Swiss National Science Foundation (grant no. PCEFP3_181282; to M.S.); ERC-2017-STG (grant agreement no. 758448; to N.G.); Swiss National Science Foundation and ERC-2016-CoG (grant agreement no. 725850) (A.R.A.); University of Bern and Inselspital University Hospital (A.R.A. and M.H.S.); ERC-2014-CoG (grant agreement no. 647725) and National Institutes of Health Brain Initiative (U19 NS107464) (both to T.F.); H2020-ICT (grant agreement no. 101016787; to T.P. and T.F.). We thank J.-C. Paterna and the VVF of the Neuroscience Center Zurich for help with virus production, M. Drobizhev (Montana State ...

Yes ; The human- and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to have expanded from a common progenitor in Africa. However, the molecular events that accompanied this emergence remain largely unknown. Here, we describe two MTBC strains isolated from patients with multidrug resistant tuberculosis, representing an as-yet-unknown lineage, named Lineage 8 (L8), seemingly restricted to the African Great Lakes region. Using genome-based phylogenetic reconstruction, we show that L8 is a sister clade to the known MTBC lineages. Comparison with other complete mycobacterial genomes indicate that the divergence of L8 preceded the loss of the cobF genome region - involved in the cobalamin/vitamin B12 synthesis - and gene interruptions in a subsequent common ancestor shared by all other known MTBC lineages. This discovery further supports an East African origin for the MTBC and provides additional molecular clues on the ancestral genome reduction associated with adaptation to a pathogenic lifestyle. ; This work was supported by EDCTP2 grant DRIA2014-326—DIAMA of the European Union, the Belgian General Directorate for Development Cooperation (PhD fellowship to J.C.S.N.), Grant ANR-16-CE35-0009 from Agence Nationale de la Recherche, the Swiss National Science Foundation (Grants 310030_188888, IZRJZ3_164171, IZLSZ3_170834 and CRSII5_177163), and the European Research Council (309540-EVODRTB). The views and opinions of authors expressed herein do not necessarily state or reflect those of EDCTP. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.