77 research outputs found

    Fat and Sugar—A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease

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    Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver damage in patients are not fully understood. A deeper investigation of NAFLD pathogenesis is possible due to the many different animal models developed recently. In this review, we present a comparative overview of the most common dietary NAFLD rodent models with respect to their metabolic phenotype and morphological manifestation. Moreover, we describe similarities and controversies concerning the effect of NAFLD-inducing diets on mitochondria as well as mitochondria-derived oxidative stress in the progression of NAFLD

    Recent glitches detected in the Crab pulsar

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    From 2000 to 2010, monitoring of radio emission from the Crab pulsar at Xinjiang Observatory detected a total of nine glitches. The occurrence of glitches appears to be a random process as described by previous researches. A persistent change in pulse frequency and pulse frequency derivative after each glitch was found. There is no obvious correlation between glitch sizes and the time since last glitch. For these glitches ΔΜp\Delta\nu_{p} and ΔΜ˙p\Delta\dot{\nu}_{p} span two orders of magnitude. The pulsar suffered the largest frequency jump ever seen on MJD 53067.1. The size of the glitch is ∌\sim 6.8 ×10−6\times 10^{-6} Hz, ∌\sim 3.5 times that of the glitch occured in 1989 glitch, with a very large permanent changes in frequency and pulse frequency derivative and followed by a decay with time constant ∌\sim 21 days. The braking index presents significant changes. We attribute this variation to a varying particle wind strength which may be caused by glitch activities. We discuss the properties of detected glitches in Crab pulsar and compare them with glitches in the Vela pulsar.Comment: Accepted for publication in Astrophysics & Space Scienc

    Sensitizing thermochemotherapy with a PARP1-inhibitor

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    Cis-diamminedichloroplatinum(II) (cisplatin, cDDP) is an effective chemotherapeutic agent that induces DNA double strand breaks (DSBs), primarily in replicating cells. Generally, such DSBs can be repaired by the classical or backup non-homologous end joining (c-NHEJ/b-NHEJ) or homologous recombination (HR). Therefore, inhibiting these pathways in cancer cells should enhance the efficiency of cDDP treatments. Indeed, inhibition of HR by hyperthermia (HT) sensitizes cancer cells to cDDP and in the Netherlands this combination is a standard treatment option for recurrent cervical cancer after previous radiotherapy. Additionally, cDDP has been demonstrated to disrupt c-NHEJ, which likely further increases the treatment efficacy. However, if one of these pathways is blocked, DSB repair functions can be sustained by the Poly-(ADP-ribose)-polymerase1 (PARP1)-dependent b-NHEJ. Therefore, disabling b-NHEJ should, in principle, further inhibit the repair of cDDP-induced DNA lesions and enhance the toxicity of thermochemotherapy. To explore this hypothesis, we treated a panel of cancer cell lines with HT, cDDP and a PARP1-i and measured various end-point relevant in cancer treatment. Our results demonstrate that PARP1-i does not considerably increase the efficacy of HT combined with standard, commonly used cDDP concentrations. However, in the presence of a PARP1-i, ten-fold lower concentration of cDDP can be used to induce similar cytotoxic effects. PARP1 inhibition may thus permit a substantial lowering of cDDP concentrations without diminishing treatment efficacy, potentially reducing systemic side effects

    Enhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient tumour cells with hyperthermia

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    Background: Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA double strand breaks, which are generally repaired by homologous recombination (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be temporarily inhibited by hyperthermia, thereby inducing synthetic lethal conditions in every tumor type. Since cisplatin is successfully used combined with hyperthermia (thermochemotherapy), we investigated the effectiveness of combining PARP1-i with thermochemotherapy. Results: The in vitro data demonstrate a decreased in cell survival after addition of PARP1-i to thermochemotherapy, which can be explained by increased DNA damage induction and less DSB repair. These in vitro findings are in line with in vivo model, in which a decreased tumor growth is observed upon addition of PARP1-i. Materials and Methods: Survival of three HR-proficient cell lines after cisplatin, hyperthermia and/or PARP1-i was studied. Cell cycle analyses, quantification of Îł-H2AX foci and apoptotic assays were performed to understand these survival data. The effects of treatments were further evaluated by monitoring tumor responses in an in vivo rat model. Conclusions: Our results in HR-proficient cell lines suggest that PARP1-i combined with thermochemotherapy can be a promising clinical approach for all tumors independent of HR status

    Flavor changing Z-decays from scalar interactions at a Giga-Z Linear Collider

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    The flavor changing decay Z -> d_I \bar{d}_J is investigated with special emphasis on the b \bar{s} final state. Various models for flavor violation are considered: two Higgs doublet models (2HDM's), supersymmetry (SUSY) with flavor violation in the up and down-type squark mass matrices and SUSY with flavor violation mediated by R-parity-violating interaction. We find that, within the SUSY scenarios for flavor violation, the branching ratio for the decay Z -> b \bar{s} can reach 10^{-6} for large \tan\beta values, while the typical size for this branching ratio in the 2HDM's considered is about two orders of magnitudes smaller at best. Thus, flavor changing SUSY signatures in radiative Z decays such as Z -> b \bar{s} may be accessible to future ``Z factories'' such as a Giga-Z version of the TESLA design.Comment: 27 pages, 15 figures, REVTeX4. A new section added and a few minor corrections were made in the tex

    Study of the lineshape of the chi(c1) (3872) state

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    A study of the lineshape of the chi(c1) (3872) state is made using a data sample corresponding to an integrated luminosity of 3 fb(-1) collected in pp collisions at center-of-mass energies of 7 and 8 TeV with the LHCb detector. Candidate chi(c1)(3872) and psi(2S) mesons from b-hadron decays are selected in the J/psi pi(+)pi(-) decay mode. Describing the lineshape with a Breit-Wigner function, the mass splitting between the chi(c1 )(3872) and psi(2S) states, Delta m, and the width of the chi(c1 )(3872) state, Gamma(Bw), are determined to be (Delta m=185.598 +/- 0.067 +/- 0.068 Mev,)(Gamma BW=1.39 +/- 0.24 +/- 0.10 Mev,) where the first uncertainty is statistical and the second systematic. Using a Flatte-inspired model, the mode and full width at half maximum of the lineshape are determined to be (mode=3871.69+0.00+0.05 MeV.)(FWHM=0.22-0.04+0.13+0.07+0.11-0.06-0.13 MeV, ) An investigation of the analytic structure of the Flatte amplitude reveals a pole structure, which is compatible with a quasibound D-0(D) over bar*(0) state but a quasivirtual state is still allowed at the level of 2 standard deviations

    Measurement of the CKM angle γγ in B±→DK±B^\pm\to D K^\pm and B±→Dπ±B^\pm \to D π^\pm decays with D→KS0h+h−D \to K_\mathrm S^0 h^+ h^-

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    A measurement of CPCP-violating observables is performed using the decays B±→DK±B^\pm\to D K^\pm and B±→Dπ±B^\pm\to D \pi^\pm, where the DD meson is reconstructed in one of the self-conjugate three-body final states KSπ+π−K_{\mathrm S}\pi^+\pi^- and KSK+K−K_{\mathrm S}K^+K^- (commonly denoted KSh+h−K_{\mathrm S} h^+h^-). The decays are analysed in bins of the DD-decay phase space, leading to a measurement that is independent of the modelling of the DD-decay amplitude. The observables are interpreted in terms of the CKM angle Îł\gamma. Using a data sample corresponding to an integrated luminosity of 9 fb−19\,\text{fb}^{-1} collected in proton-proton collisions at centre-of-mass energies of 77, 88, and 13 TeV13\,\text{TeV} with the LHCb experiment, Îł\gamma is measured to be (68.7−5.1+5.2)∘\left(68.7^{+5.2}_{-5.1}\right)^\circ. The hadronic parameters rBDKr_B^{DK}, rBDπr_B^{D\pi}, ÎŽBDK\delta_B^{DK}, and ÎŽBDπ\delta_B^{D\pi}, which are the ratios and strong-phase differences of the suppressed and favoured B±B^\pm decays, are also reported

    Detachment tectonics during continental rifting off the west Iberia Atlantic margin: seismic reflection and drilling constraints

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    Lithospheric extension and thinning leading to complete continental rupture and the formation of rifted margins are among the most fundamental geological processes. The west Iberia Atlantic margin represents a type-example of a non-volcanic rifted margin, and is an ideal site to study the nature of lithospheric extension. It is relatively sediment-starved and exhibits in the Galicia Bank area landward tilted crustal blocks, which are bound by west-dipping normal faults. Seismic time sections image these faults underlain by an apparently undulating and discontinuous bright reflection, the S reflector, terminating further west near the ocean-continent boundary (OCT). This boundary is marked by a mantle outcrop shown by drilling to consist of serpentinised peridotite. Similar observations in the Iberia Abyssal Plain had not been reported until the beginning of this study, except the hypothesis of mantle material at the OCT proved in 1993 by drilling. (orig.)Available from TIB Hannover: RR 1846(37) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDeutsche Forschungsgemeinschaft (DFG), Bonn (Germany)DEGerman
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