Merida, I. | bioRxiv Science

bioRxiv2020

CERMEP-IDB-MRXFDG: A database of 37 normal adult human brain FDG PET, T1 and FLAIR MRI, and CT images available for research

We present a database of cerebral PET FDG and anatomical MRI for 37 normal adult human subjects (CERMEP-IDB-MRXFDG). Thirty-nine participants underwent [18F]FDG PET/CT and MRI, resulting in [18F]FDG PET, T1 MPRAGE MRI, FLAIR MRI, and CT images. Two participants were excluded after visual quality control. We describe the acquisition parameters, the image processing pipeline and provide participants individual demographics (mean age 38 {+/-} 11.5 years, range 23-65, 20 women). Volumetric analysis of the 37 T1 MRIs showed results in line with the literature. A leave-one-out assessment of the 37 FDG images using Statistical Parametric Mapping (SPM) yielded a low number of false positives after exclusion of artefacts. The database is stored in three different formats, following the BIDS common specification: 1) DICOM (data not processed), 2) NIFTI (multimodal images coregistered to PET subject space), 3) NIFTI normalized (images normalized to MNI space). Bona fide researchers can request access to the database via a short form.

neuroscience↗

bioRxiv2020

Diacylglycerol kinase ζ deficiency triggers early signs of aplastic anemia in mice

Acquired aplastic anemia (AA) is a rare blood disorder that results from immune-mediated destruction of bone marrow (BM) progenitor cells. Improved understanding of the mechanisms that favor T cell attack in BM could help to improve early diagnosis and disease treatment. Diacylglycerol kinase {zeta} (DGK{zeta}) limits T cell responses through phosphorylation of diacylglycerol into phosphatidic acid. This reaction attenuates diacylglycerol-dependent activation of the Ras/ERK/CD69 and PKC{theta}/NF{kappa}B pathways in response to antigen. Here we show that, in contrast to the lack of basal activation observed in peripheral lymphoid organs, DGK{zeta}-/- mice showed increased numbers of activated T cells in BM, together with a significant increase in IFN{gamma} as well as perforin and granzyme B and C levels. The enhanced presence of T cells in DGK{zeta}-/- mouse BM correlates with reduced BM cellularity, impaired hematopoiesis, and lower frequency of circulating red cells, granulocytes, and platelets. Our studies coincide with the recent characterization of lower DGK{zeta} expression in T cells isolated from the BM of patients with acquired AA, and suggest that limited DGK{zeta} expression and/or functions predispose to T cell-mediated BM destruction. This study identifies the BM as a niche particularly sensitive to DGK{zeta} deficiency and indicates that this mouse model could be of interest for studying the mechanism that contributes to AA development. Key pointsO_LIDGK{zeta}-deficiency in mice results in larger numbers of CD69-positive T cells in bone marrow, with enhanced expression of IFN{gamma} and lytic enzymes. C_LIO_LIDGK{zeta} loss recapitulates many clinical aspects of human aplastic anemia, identifying a critical hub for immune system-dependent bone marrow failure. C_LI Visual abstract O_FIG O_LINKSMALLFIG WIDTH=140 HEIGHT=200 SRC="FIGDIR/small/136390v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@d485b2org.highwire.dtl.DTLVardef@9599c1org.highwire.dtl.DTLVardef@1a17842org.highwire.dtl.DTLVardef@1de640d_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗