RIPK1 protects from TNF-α-mediated liver damage during hepatitis

Cell death of hepatocytes is a prominent characteristic in the pathogenesis of liver disease, while hepatolysis is a starting point of inflammation in hepatitis and loss of hepatic function. However, the precise molecular mechanisms of hepatocyte cell death, the role of the cytokines of hepatic microenvironment and the involvement of intracellular kinases, remain unclear. Tumor necrosis factor alpha (TNF-alpha) is a key cytokine involved in cell death or survival pathways and the role of RIPK1 has been associated to the TNF-alpha-dependent signaling pathway. We took advantage of two different deficient mouse lines, the RIPK1 kinase dead knock-in mice (Ripk1K45A) and the conditional knockout mice lacking RIPK1 only in liver parenchymal cells (Ripk1LPC-KO), to characterize the role of RIPK1 and TNF-alpha in hepatitis induced by concanavalin A (ConA). Our results show that RIPK1 is dispensable for liver homeostasis under steady-state conditions but in contrast, RIPK1 kinase activity contributes to caspase-independent cell death induction following ConA injection and RIPK1 also serves as a scaffold, protecting hepatocytes from massive apoptotic cell death in this model. In the Ripk1LPC-KO mice challenged with ConA, TNF-alpha triggers apoptosis, responsible for the observed severe hepatitis. Mechanism potentially involves both TNF-independent canonical NF-kappa B activation, as well as TNF-dependent, but canonical NF-kappa B-independent mechanisms. In conclusion, our results suggest that RIPK1 kinase activity is a pertinent therapeutic target to protect liver against excessive cell death in liver diseases

Odor Perception in Children with Autism Spectrum Disorder and its Relationship to Food Neophobia

Atypical sensory functioning in Autism Spectrum Disorder (ASD) has been well documented in the last decade for the visual, tactile and auditory systems, but olfaction in ASD is still understudied. The aim of the present study was to examine whether children with ASD and neuro-typically (NT) developed children differed in odor perception, at the cognitive (familiarity and identification ability), sensorimotor (olfactory exploration) and affective levels (hedonic evaluation). Because an important function of the sense of smell is its involvement in eating, from food selection to appreciation and recognition, a potential link between odor perception and food neophobia was also investigated. To these ends, 10 children between 6 and 13 years old diagnosed with ASD and 10 NT control children were tested. To compare performance, 16 stimuli were used and food neophobia was assessed by the parents on a short food neophobia scale. Results revealed that (i) significant hedonic discrimination between attractive and aversive odors was observed in NT (p=0.005; d=2.378) and ASD children (p=0.042; d=0.941), and (ii) hedonic discrimination level was negatively correlated with food neophobia scores in ASD (p=0.007) but not NT children. In conclusion, this study offers new insights into odor perception in ASD children, highlighting a relationship between odor hedonic reactivity and eating behavior. This opens up new perspectives on both (i) the role of olfaction in the construction of eating behavior in ASD children, and (ii) the measurement and meaning of food neophobia in this population

Cell Division by Longitudinal Scission in the Insect Endosymbiont

Spiroplasma bacteria are highly motile bacteria with no cell wall and a helical morphology. This clade includes many vertically transmitted insect endosymbionts, including Spiroplasma poulsonii, a natural endosymbiont of Drosophila melanogaster. S. poulsonii bacteria are mainly found in the hemolymph of infected female flies and exhibit efficient vertical transmission from mother to offspring. As is the case for many facultative endosymbionts, S. poulsonii can manipulate the reproduction of its host; in particular, S. poulsonii induces male killing in Drosophila melanogaster. Here, we analyze the morphology of S. poulsonii obtained from the hemolymph of infected Drosophila. This endosymbiont was not only found as long helical filaments, as previously described, but was also found in a Y-shaped form. The use of electron microscopy, immunogold staining of the FtsZ protein, and antibiotic treatment unambiguously linked the Y shape of S. poulsonii to cell division. Observation of the Y shape in another Spiroplasma, S. citri, and anecdotic observations from the literature suggest that cell division by longitudinal scission might be prevalent in the Spiroplasma clade. Our study is the first to report the Y-shape mode of cell division in an endosymbiotic bacterium and adds Spiroplasma to the so far limited group of bacteria known to utilize this cell division mod

Cholecystokinin B Receptor from Human Jurkat Lymphoblastic T Cells Is Involved in Activator Protein-1-Responsive Gene Activation

SUMMARY The aim of this study was to analyze the role of cholecystokinin (CCK B ) receptor in human lymphoblastic Jurkat T cells. We investigated the trophic effect resulting from activation of such a receptor by using the reporter gene strategy. For this purpose, we transiently transfected Jurkat T cells with the reporter plasmid p[(TRE)3-tk-Luc] and found that CCK-8 was able to dose-dependently induce luciferase expression related to activator protein-1 (AP-1) activation with a maximal response identical to that obtained with compounds known to activate AP-1 complex (quantitatively, the same level of induction was obtained with 1 nM 12-O-tetradecanoylphorbol-13-acetate, 100 M diacylglycerol, or 4 nM epidermal growth factor). The involvement of the CCK B receptor in such a stimulation was demonstrated by the inhibiting effect of the selective CCK B receptor antagonist 158. This effect was confirmed in COS-7 cells transfected with the cDNA of CCK B receptor cloned from Jurkat T cells. To better understand the AP-1-dependent luciferase expression in Jurkat T cells, we tested two specific inhibitors of serine/threonine phosphatases-1 and -2A: okadaic acid and calyculin A. These compounds strongly increased the phorbol-12-myristate-13-acetate response, whereas we have not observed a contribution of phosphatase inhibitors on a CCK-8-induced luciferase activity. To confirm that CCK B receptors are involved in AP-1 response, we investigated the CCK-8 effect on interleukin-2 expression, a natural endogenous gene regulated by several factors, including AP-1. In Jurkat T cells activated by phorbol-12-myristate-13-acetate and phytohemagglutinin, CCK-8 induced IL-2 expression. This induction was abolished by PD-135,158. Our results indicate that CCK-8 exerts a trophic effect in Jurkat T cells through stimulation of CCK B receptors by modulation of expression of AP-1-regulated genes. Several studies have shown that various gastrointestinal peptides may be involved in the control of proliferation of various tissues and neoplastic cells (1). For example, CCK was shown to increase growth of tumors in nude mice bearing transplanted pancreatic cancer tissues (2). CCK is also known to increase the number of animals developing nitrosamine-induced pancreatic cancers (3), and CCK was shown to increase the rate of growth of cultured pancreatic cancer cells (2). Similar observations were described for bombesin/ gastrin-releasing peptide in human glioblastoma in vitro and in vivo in small-cell lung carcinoma, prostatic, mammary, and pancreatic cancer cell lines (1). In addition, gastrointestinal peptides can function as autocrine growth factors in neoplastic tissues as shown for bombesin/gastrin-releasing peptide in small-cell lung carcinoma cells, for gastrin an

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Pathogenic Mouse Hepatitis Virus or Poly(I:C) Induce IL-33 in Hepatocytes in Murine Models of Hepatitis.

International audienceThe IL-33/ST2 axis is known to be involved in liver pathologies. Although, the IL-33 levels increased in sera of viral hepatitis patients in human, the cellular sources of IL-33 in viral hepatitis remained obscure. Therefore, we aimed to investigate the expression of IL-33 in murine fulminant hepatitis induced by a Toll like receptor (TLR3) viral mimetic, poly(I:C) or by pathogenic mouse hepatitis virus (L2-MHV3). The administration of poly(I:C) plus D-galactosamine (D-GalN) in mice led to acute liver injury associated with the induction of IL-33 expression in liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells (VEC), while the administration of poly(I:C) alone led to hepatocyte specific IL-33 expression in addition to vascular IL-33 expression. The hepatocyte-specific IL-33 expression was down-regulated in NK-depleted poly(I:C) treated mice suggesting a partial regulation of IL-33 by NK cells. The CD1d KO (NKT deficient) mice showed hepatoprotection against poly(I:C)-induced hepatitis in association with increased number of IL-33 expressing hepatocytes in CD1d KO mice than WT controls. These results suggest that hepatocyte-specific IL-33 expression in poly(I:C) induced liver injury was partially dependent of NK cells and with limited role of NKT cells. In parallel, the L2-MHV3 infection in mice induced fulminant hepatitis associated with up-regulated IL-33 expression as well as pro-inflammatory cytokine microenvironment in liver. The LSEC and VEC expressed inducible expression of IL-33 following L2-MHV3 infection but the hepatocyte-specific IL-33 expression was only evident between 24 to 32h of post infection. In conclusion, the alarmin cytokine IL-33 was over-expressed during fulminant hepatitis in mice with LSEC, VEC and hepatocytes as potential sources of IL-33

The 13th Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-IV Survey Mapping Nearby Galaxies at Apache Point Observatory

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in July 2014. It pursues three core programs: APOGEE-2,MaNGA, and eBOSS. In addition, eBOSS contains two major subprograms: TDSS and SPIDERS. This paper describes the first data release from SDSS-IV, Data Release 13 (DR13), which contains new data, reanalysis of existing data sets and, like all SDSS data releases, is inclusive of previously released data. DR13 makes publicly available 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA,the first data released from this survey. It includes new observations from eBOSS, completing SEQUELS. In addition to targeting galaxies and quasars, SEQUELS also targeted variability-selected objects from TDSS and X-ray selected objects from SPIDERS. DR13 includes new reductions ofthe SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification. DR13 releases new reductions of the APOGEE-1data from SDSS-III, with abundances of elements not previously included and improved stellar parameters for dwarf stars and cooler stars. For the SDSS imaging data, DR13 provides new, more robust and precise photometric calibrations. Several value-added catalogs are being released in tandem with DR13, in particular target catalogs relevant for eBOSS, TDSS, and SPIDERS, and an updated red-clump catalog for APOGEE.This paper describes the location and format of the data now publicly available, as well as providing references to the important technical papers that describe the targeting, observing, and data reduction. The SDSS website, http://www.sdss.org, provides links to the data, tutorials and examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ~6-year operations of SDSS-IV.PostprintPeer reviewe