65 research outputs found

    Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma

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    Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients

    Observation of Two New Excited Ξb0 States Decaying to Λb0 K-π+

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    Two narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]<2.20(2.56) and Γ[Ξb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

    Angular Analysis of the B+ -> K*(+)mu(+) mu(-) Decay

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    We present an angular analysis of the B + → K * + ( → K 0 S π + ) μ + μ − decay using 9     fb − 1 of p p collision data collected with the LHCb experiment. For the first time, the full set of C P -averaged angular observables is measured in intervals of the dimuon invariant mass squared. Local deviations from standard model predictions are observed, similar to those in previous LHCb analyses of the isospin-partner B 0 → K * 0 μ + μ − decay. The global tension is dependent on which effective couplings are considered and on the choice of theory nuisance parameters

    Precise determination of the B-s(0)-B-s(-0) oscillation frequency

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    Mesons comprising a beauty quark and a strange quark can oscillate between particle (B0s) and antiparticle (B0s) flavour eigenstates, with a frequency given by the mass difference between heavy and light mass eigenstates, deltams. Here we present ameasurement of deltams using B0s2DsPi decays produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The oscillation frequency is found to be deltams = 17.7683 +- 0.0051 +- 0.0032 ps-1, where the first uncertainty is statistical and the second systematic. This measurement improves upon the current deltams precision by a factor of two. We combine this result with previous LHCb measurements to determine deltams = 17.7656 +- 0.0057 ps-1, which is the legacy measurement of the original LHCb detector.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2021-005.html (LHCb public pages

    Search for the doubly heavy baryons Omega(0)(bc) and Xi(0)(bc) decaying to Lambda(+)(c)pi(-) and Xi(+)(c)pi-

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    Abstract available from publisher's website

    Search for time-dependent CPCP violation in D0K+KD^0 \to K^+ K^- and D0π+πD^0 \to π^+ π^- decays

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    A search for time-dependent violation of the charge-parity symmetry in D0K+KD^0 \to K^+ K^- and D0π+πD^0 \to \pi^+ \pi^- decays is performed at the LHCb experiment using proton-proton collision data recorded from 2015 to 2018 at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb1^{-1}. The D0D^0 meson is required to originate from a D(2010)+D0π+D^*(2010)^+ \to D^0 \pi^+ decay, such that its flavour at production is identified by the charge of the accompanying pion. The slope of the time-dependent asymmetry of the decay rates of D0D^0 and Dˉ0\bar{D}^0 mesons into the final states under consideration is measured to be ΔYK+K=(2.3±1.5±0.3)×104\Delta Y_{K^+ K^-} = (-2.3 \pm 1.5 \pm 0.3) \times 10^{-4}, ΔYπ+π=(4.0±2.8±0.4)×104\Delta Y_{\pi^+ \pi^-} = (-4.0 \pm 2.8 \pm 0.4)\times 10^{-4}, where the first uncertainties are statistical and the second are systematic. These results are compatible with the conservation of the charge-parity symmetry at the level of 2 standard deviations and improve the precision by nearly a factor of two
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