3,731 research outputs found

    Modulation of Ku70/80, clusterin/ApoJ isoforms and Bax expression in indocyanine-green-mediated photo-oxidative cell damage

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    In order to characterize the biological effects and molecular mechanism underlying indocyanine-green (ICG)-mediated photo-oxidative cell damage, human cultured retinal pigmented epithelium (RPE) cells preloaded with ICG were exposed to 810-nm laser irradiation. Cell viability and death induction were examined, as well as the modulation of proteins involved in cell death and DNA repair

    Measurement of the tt production cross section in the dilepton channel in pp collisions at √s = 8 TeV

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    Journal of High Energy Physics 2012.2 (2014): 024 reproduced by permission of Scuola Internazionale Superiore di Studi Avanzati (SISSA)ArtĂ­culo escrito por un elevado nĂșmero de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboraciĂłn, si le hubiere, y los autores pertenecientes a la UAMThe top-antitop quark (tt̄) production cross section is measured in proton-proton collisions at √s = 8 TeV with the CMS experiment at the LHC, using a data sample corresponding to an integrated luminosity of 5.3 fb -1. The measurement is performed by analysing events with a pair of electrons or muons, or one electron and one muon, and at least two jets, one of which is identified as originating from hadronisation of a bottom quark. The measured cross section is 239 ± 2 (stat.) ± 11 (syst.) ± 6 (lum.) pb, for an assumed top-quark mass of 172.5 GeV, in agreement with the prediction of the standard mode

    Inhibition of Akt signaling in hepatoma cells induces apoptotic cell death independent of Akt activation status

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    Cataloged from PDF version of article.The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is involved in cell survival and anti-apoptotic signaling. Akt has been shown to be constitutively expressed in a variety of human tumors including hepatocellular carcinoma (HCC). In this report we analyzed the status of Akt pathway in three HCC cell lines, and tested cytotoxic effects of Akt pathway inhibitors LY294002, Wortmannin and Inhibitor VIII. In Mahlavu human hepatoma cells Akt was constitutively activated, as demonstrated by its Ser473 phosphorylation, downstream hyperphosphorylation of BAD on Ser136, and by a specific cell-free kinase assay. In contrast, Huh7 and HepG2 did not show hyperactivation when tested by the same criteria. Akt enzyme hyperactivation in Mahlavu was associated with a loss of PTEN protein expression. Akt signaling was inhibited by the upstream kinase inhibitors, LY294002, Wortmannin, as well as by the specific Akt Inhibitor VIII in all three hepatoma cell lines. Cytotoxicity assays with Akt inhibitors in the same cell lines indicated that they were all sensitive, but with different IC50 values as assayed by RT-CES. We also demonstrated that the cytotoxic effect was through apoptotic cell death. Our findings provide evidence for its constitutive activation in one HCC cell line, and that HCC cell lines, independent of their Akt activation status respond to Akt inhibitors by apoptotic cell death. Thus, Akt inhibition may be considered as an attractive therapeutic intervention in liver cancer. © Springer Science+Business Media, LLC 2010

    "It All Ended in an Unsporting Way": Serbian Football and the Disintegration of Yugoslavia, 1989-2006

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    Part of a wider examination into football during the collapse of Eastern European Communism between 1989 and 1991, this article studies the interplay between Serbian football and politics during the period of Yugoslavia's demise. Research utilizing interviews with individuals directly involved in the Serbian game, in conjunction with contemporary Yugoslav media sources, indicates that football played an important proactive role in the revival of Serbian nationalism. At the same time the Yugoslav conflict, twinned with a complex transition to a market economy, had disastrous consequences for football throughout the territories of the former Yugoslavia. In the years following the hostilities the Serbian game has suffered decline, major financial hardship and continuing terrace violence, resulting in widespread nostalgia for the pre-conflict era

    Aharonov-Bohm effect and resonances in the circular quantum billiard with two leads

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    We calculate the conductance through a circular quantum billiard with two leads and a point magnetic flux at the center. The boundary element method is used to solve the Schrodinger equation of the scattering problem, and the Landauer formula is used to calculate the conductance from the transmission coefficients. We use two different shapes of leads, straight and conic, and find that the conductance is affected by lead geometry, the relative positions of the leads and the magnetic flux. The Aharonov-Bohm effect can be seen from shifts and splittings of fluctuations. When the flux is equal to (h/2e) and the angle between leads is 180 degree, the conductance tends to be suppressed to zero in the low energy range due to the Aharonov-Bohm effect.Comment: LaTeX2e, 8 pages, 6 figures, submitted to Phys. Rev. B (Two references added. A discussion on discrete symmetries removed.

    AKT1 (v-akt murine thymoma viral oncogene homolog 1)

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    Review on AKT1 (v-akt murine thymoma viral oncogene homolog 1), with data on DNA, on the protein encoded, and where the gene is implicated

    From Bed to Bench and Back: TNF-α, IL-23/IL-17A, and JAK-Dependent Inflammation in the Pathogenesis of Psoriatic Synovitis

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    Psoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease with a burdensome impact on quality of life and substantial healthcare costs. To date, pharmacological interventions with different mechanisms of action, including conventional synthetic (cs), biological (b), and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs), have been proven efficacious, despite a relevant proportion of failures. The current approach in clinical practice and research is typically “predictive”: the expected response is based on stratification according to clinical, imaging, and laboratory data, with a “heuristic” approach based on “trial and error”. Several available therapeutic options target the TNF-α pathway, while others are directed against the IL-23/IL-17A axis. Janus kinase inhibitors (JAKis), instead, simultaneously block different pathways, endowing these drugs with a potentially “broad-spectrum” mechanism of action. It is not clear, however, whether targeting a specific pathway (e.g., TNF-α or the IL-23/IL-17 axis) could result in discordant effects over other approaches. In particular, in the case of “refractory to a treatment” patients, other pathways might be hyperactivated, with opposing, synergistic, or redundant biological significance. On the contrary, refractory states could be purely resistant to treatment as a whole. Since chronic synovitis is one of the primary targets of inflammation in PsA, synovial biomarkers could be useful in depicting specific biological characteristics of the inflammatory burden at the single-patient level, and despite not yet being implemented in clinical practice, these biomarkers might help in selecting the proper treatment. In this narrative review, we will provide an up-to-date overview of the knowledge in the field of psoriatic synovitis regarding studies investigating the relationships among different activated proinflammatory processes suitable for targeting by different available drugs. The final objective is to clarify the state of the art in the field of personalized medicine for psoriatic disease, aiming at moving beyond the current treatment schedules toward a patient-centered approach

    Defective endoplasmic reticulum-mitochondria contacts and bioenergetics in SEPN1-related myopathy

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    SEPN1-related myopathy (SEPN1-RM) is a muscle disorder due to mutations of the SEPN1 gene, which is characterized by muscle weakness and fatigue leading to scoliosis and life-threatening respiratory failure. Core lesions, focal areas of mitochondria depletion in skeletal muscle fibers, are the most common histopathological lesion. SEPN1-RM underlying mechanisms and the precise role of SEPN1 in muscle remained incompletely understood, hindering the development of biomarkers and therapies for this untreatable disease. To investigate the pathophysiological pathways in SEPN1-RM, we performed metabolic studies, calcium and ATP measurements, super-resolution and electron microscopy on in vivo and in vitro models of SEPN1 deficiency as well as muscle biopsies from SEPN1-RM patients. Mouse models of SEPN1 deficiency showed marked alterations in mitochondrial physiology and energy metabolism, suggesting that SEPN1 controls mitochondrial bioenergetics. Moreover, we found that SEPN1 was enriched at the mitochondria-associated membranes (MAM), and was needed for calcium transients between ER and mitochondria, as well as for the integrity of ER-mitochondria contacts. Consistently, loss of SEPN1 in patients was associated with alterations in body composition which correlated with the severity of muscle weakness, and with impaired ER-mitochondria contacts and low ATP levels. Our results indicate a role of SEPN1 as a novel MAM protein involved in mitochondrial bioenergetics. They also identify a systemic bioenergetic component in SEPN1-RM and establish mitochondria as a novel therapeutic target. This role of SEPN1 contributes to explain the fatigue and core lesions in skeletal muscle as well as the body composition abnormalities identified as part of the SEPN1-RM phenotype. Finally, these results point out to an unrecognized interplay between mitochondrial bioenergetics and ER homeostasis in skeletal muscle. They could therefore pave the way to the identification of biomarkers and therapeutic drugs for SEPN1-RM and for other disorders in which muscle ER-mitochondria cross-talk are impaired
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