Measurement of CP asymmetries and branching fraction ratios of B− decays to two charm mesons

The $CP$ asymmetries of seven $B^-$ decays to two charm mesons are measured using data corresponding to an integrated luminosity of $9\text{fb}^{-1}$ of proton-proton collisions collected by the LHCb experiment. Decays involving a $D^{*0}$ or $D^{*-}_s$ meson are analysed by reconstructing only the $D^0$ or $D^-_s$ decay products. This paper presents the first measurement of $\mathcal{A}^{CP}(B^- \rightarrow D^{*-}_s D^0)$ and $\mathcal{A}^{CP}(B^- \rightarrow D^{-}_s D^{*0})$, and the most precise measurement of the other five $CP$ asymmetries. There is no evidence of $CP$ violation in any of the analysed decays. Additionally, two ratios between branching fractions of selected decays are measured.The CP asymmetries of seven B$^{−}$ decays to two charm mesons are measured using data corresponding to an integrated luminosity of 9 fb$^{−1}$ of proton-proton collisions collected by the LHCb experiment. Decays involving a D$^{*0}$ or ${D}_s^{\ast -}$ meson are analysed by reconstructing only the D$^{0}$ or ${D}_s^{-}$ decay products. This paper presents the first measurement of $\mathcal{A} ^{CP}$(B$^{−}$→${D}_s^{\ast -}$D$^{0}$) and $\mathcal{A} ^{CP}$(B$^{−}$→${D}_s^{-}$D$^{∗0}$), and the most precise measurement of the other five CP asymmetries. There is no evidence of CP violation in any of the analysed decays. Additionally, two ratios between branching fractions of selected decays are measured.[graphic not available: see fulltext]The $CP$ asymmetries of seven $B^-$ decays to two charm mesons are measured using data corresponding to an integrated luminosity of $9\text{ fb}^{-1}$ of proton-proton collisions collected by the LHCb experiment. Decays involving a $D^{*0}$ or $D^{*-}_s$ meson are analysed by reconstructing only the $D^0$ or $D^-_s$ decay products. This paper presents the first measurement of $\mathcal{A}^{CP}(B^- \rightarrow D^{*-}_s D^0)$ and $\mathcal{A}^{CP}(B^- \rightarrow D^{-}_s D^{*0})$, and the most precise measurement of the other five $CP$ asymmetries. There is no evidence of $CP$ violation in any of the analysed decays. Additionally, two ratios between branching fractions of selected decays are measured

The LHCb upgrade I

The LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

Leptin is induced in the ischemic cerebral cortex and exerts neuroprotection through NF-kappaB/c-Rel-dependent transcription

BACKGROUND AND PURPOSE: Leptin is an adipose hormone endowed with angiopoietic, neurotrophic, and neuroprotective properties. We tested the hypothesis that leptin might act as an endogenous mediator of recovery after ischemic stroke and investigated whether nuclear transcription factors kappaB activation is involved in leptin-mediated neuroprotection. METHODS: The antiapoptotic effects of leptin were evaluated in cultured mouse cortical neurons from wild-type or NF-kappaB/c-Rel(-/-) mice exposed to oxygen-glucose deprivation. Wild-type, c-Rel(-/-) and leptin-deficient ob/ob mice were subjected to permanent middle cerebral artery occlusion. Leptin production was measured in brains from wild-type mice with quantitative reverse transcriptase-polymerase chain reaction and immunostaining. Mice received a leptin bolus (20 microg/g) intraperitoneally at the onset of ischemia. RESULTS: Leptin treatment activated the nuclear translocation of nuclear transcription factors kappaB dimers containing the c-Rel subunit, induced the expression of the antiapoptotic c-Rel target gene Bcl-xL in both control and oxygen-glucose deprivation conditions, and counteracted the oxygen-glucose deprivation-mediated apoptotic death of cultured cortical neurons. Leptin-mediated Bcl-xL induction and neuroprotection against oxygen-glucose deprivation were hampered in cortical neurons from c-Rel(-/-) mice. Leptin mRNA was induced and the protein was detectable in microglia/macrophage cells from the ischemic penumbra of wild-type mice subjected to permanent middle cerebral artery occlusion. Ob/ob mice were more susceptible than wild-type mice to the permanent middle cerebral artery occlusion injury. Leptin injection significantly reduced the permanent middle cerebral artery occlusion-mediated cortical damage in wild-type and ob/ob mice, but not in c-Rel(-/-) mice. CONCLUSIONS: Leptin acts as an endogenous mediator of neuroprotection during cerebral ischemia. Exogenous leptin administration protects against ischemic neuronal injury in vitro and in vivo in a c-Rel-dependent manner

Leptin is induced in ischemic cerebral cortex and exerts neuroprotection via NF-κB/c-Rel-dependent transcription.

Background and Purpose— Leptin is an adipose hormone endowed with angiopoietic, neurotrophic, and neuroprotective properties. We tested the hypothesis that leptin might act as an endogenous mediator of recovery after ischemic stroke and investigated whether nuclear transcription factors κB activation is involved in leptin-mediated neuroprotection. Methods— The antiapoptotic effects of leptin were evaluated in cultured mouse cortical neurons from wild-type or NF-κB/c-Rel−/− mice exposed to oxygen–glucose deprivation. Wild-type, c-Rel−/− and leptin-deficient ob/ob mice were subjected to permanent middle cerebral artery occlusion. Leptin production was measured in brains from wild-type mice with quantitative reverse transcriptase–polymerase chain reaction and immunostaining. Mice received a leptin bolus (20 μg/g) intraperitoneally at the onset of ischemia. Results— Leptin treatment activated the nuclear translocation of nuclear transcription factors κB dimers containing the c-Rel subunit, induced the expression of the antiapoptotic c-Rel target gene Bcl-xL in both control and oxygen–glucose deprivation conditions, and counteracted the oxygen–glucose deprivation-mediated apoptotic death of cultured cortical neurons. Leptin-mediated Bcl-xL induction and neuroprotection against oxygen–glucose deprivation were hampered in cortical neurons from c-Rel−/− mice. Leptin mRNA was induced and the protein was detectable in microglia/macrophage cells from the ischemic penumbra of wild-type mice subjected to permanent middle cerebral artery occlusion. Ob/ob mice were more susceptible than wild-type mice to the permanent middle cerebral artery occlusion injury. Leptin injection significantly reduced the permanent middle cerebral artery occlusion-mediated cortical damage in wild-type and ob/ob mice, but not in c-Rel−/− mice. Conclusions— Leptin acts as an endogenous mediator of neuroprotection during cerebral ischemia. Exogenous leptin administration protects against ischemic neuronal injury in vitro and in vivo in a c-Rel-dependent manner

Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity

Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. We characterized the transcriptomes and epigenomes in four primary cell types: monocytes and in vitro-differentiated naive, tolerized, and trained macrophages. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and we identified pathways functionally implicated in trained immunity. beta-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in deoxyribonuclease I hypersensitive sites at cell-type-specific epigenetic loci unveiled differentiation and treatment-specific repertoires. Altogether, we provide a resource to understand the epigenetic changes that underlie innate immunity in humans

Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity

Item does not contain fulltextMonocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. We characterized the transcriptomes and epigenomes in four primary cell types: monocytes and in vitro-differentiated naive, tolerized, and trained macrophages. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and we identified pathways functionally implicated in trained immunity. beta-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in deoxyribonuclease I hypersensitive sites at cell-type-specific epigenetic loci unveiled differentiation and treatment-specific repertoires. Altogether, we provide a resource to understand the epigenetic changes that underlie innate immunity in humans