Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells.

NKT cells, defined as T cells expressing the NK cell marker NK1.1, are involved in tumor rejection and regulation of autoimmunity via the production of cytokines. We show in this study that two types of NKT cells can be defined on the basis of their reactivity to the monomorphic MHC class I-like molecule CD1d. One type of NKT cell is positively selected by CD1d and expresses a biased TCR repertoire together with a phenotype found on activated T cells. A second type of NKT cell, in contrast, develops in the absence of CD1d, and expresses a diverse TCR repertoire and a phenotype found on naive T cells and NK cells. Importantly, the two types of NKT cells segregate in distinct tissues. Whereas thymus and liver contain primarily CD1d-dependent NKT cells, spleen and bone marrow are enriched in CD1d-independent NKT cells. Collectively, our data suggest that recognition of tissue-specific ligands by the TCR controls localization and activation of NKT cells

Mitochondrial Fusion in Human Cells Is Efficient, Requires the Inner Membrane Potential, and Is Mediated by Mitofusins

Mitochondrial fusion remains a largely unknown process despite its observation by live microscopy and the identification of few implicated proteins. Using green and red fluorescent proteins targeted to the mitochondrial matrix, we show that mitochondrial fusion in human cells is efficient and achieves complete mixing of matrix contents within 12 h. This process is maintained in the absence of a functional respiratory chain, despite disruption of microtubules or after significant reduction of cellular ATP levels. In contrast, mitochondrial fusion is completely inhibited by protonophores that dissipate the inner membrane potential. This inhibition, which results in rapid fragmentation of mitochondrial filaments, is reversible: small and punctate mitochondria fuse to reform elongated and interconnected ones upon withdrawal of protonophores. Expression of wild-type or dominant-negative dynamin-related protein 1 showed that fragmentation is due to dynamin-related protein 1-mediated mitochondrial division. On the other hand, expression of mitofusin 1 (Mfn1), one of the human Fzo homologues, increased mitochondrial length and interconnectivity. This process, but not Mfn1 targeting, was dependent on the inner membrane potential, indicating that overexpressed Mfn1 stimulates fusion. These results show that human mitochondria represent a single cellular compartment whose exchanges and interconnectivity are dynamically regulated by the balance between continuous fusion and fission reactions

Theia: an advanced optical neutrino detector

© 2020, The Author(s). New developments in liquid scintillators, high-efficiency, fast photon detectors, and chromatic photon sorting have opened up the possibility for building a large-scale detector that can discriminate between Cherenkov and scintillation signals. Such a detector could reconstruct particle direction and species using Cherenkov light while also having the excellent energy resolution and low threshold of a scintillator detector. Situated deep underground, and utilizing new techniques in computing and reconstruction, this detector could achieve unprecedented levels of background rejection, enabling a rich physics program spanning topics in nuclear, high-energy, and astrophysics, and across a dynamic range from hundreds of keV to many GeV. The scientific program would include observations of low- and high-energy solar neutrinos, determination of neutrino mass ordering and measurement of the neutrino CP-violating phase δ, observations of diffuse supernova neutrinos and neutrinos from a supernova burst, sensitive searches for nucleon decay and, ultimately, a search for neutrinoless double beta decay, with sensitivity reaching the normal ordering regime of neutrino mass phase space. This paper describes Theia, a detector design that incorporates these new technologies in a practical and affordable way to accomplish the science goals described above11sci