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  • 1
    Publication Date: 2018-09-28
    Description: Correction: The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation Correction: The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation, Published online: 27 September 2018; doi:10.1038/s41388-018-0502-y Correction: The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation
    Print ISSN: 0950-9232
    Topics: Medicine
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  • 2
    Publication Date: 2018-10-10
    Description: The Fas receptor/ligand system plays a prominent role in hepatic apoptosis and hepatocyte death. Although hepatitis B virus (HBV) surface Ag (HBsAg) is the most abundant HBV protein in the liver and peripheral blood of patients with chronic HBV infection, its role in Fas-mediated hepatocyte apoptosis has not been disclosed. In this study, we report that HBsAg sensitizes HepG2 cells to agonistic anti-Fas Ab CH11-induced apoptosis through increasing the formation of SDS-stable Fas aggregation and procaspase-8 cleavage but decreasing both the expression of cellular FLIP L/S and the recruitment of FLIP L/S at the death-inducing signaling complex (DISC). Notably, HBsAg increased endoplasmic reticulum stress and consequently reduced AKT phosphorylation by deactivation of phosphoinositide-dependent kinase-1 (PDPK1) and mechanistic target of rapamycin complex 2 (mTORC2), leading to enhancement of Fas-mediated apoptosis. In a mouse model, expression of HBsAg in mice injected with recombinant adenovirus-associated virus 8 aggravated Jo2-induced acute liver failure, which could be effectively attenuated by the AKT activator SC79. Based on these results, it is concluded that HBsAg predisposes hepatocytes to Fas-mediated apoptosis and mice to acute liver failure via suppression of AKT prosurviving activity, suggesting that interventions directed at enhancing the activation or functional activity of AKT may be of therapeutic value in Fas-mediated progressive liver cell injury and liver diseases.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 3
    Publication Date: 2018-10-28
    Description: IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma, Published online: 27 October 2018; doi:10.1038/s41388-018-0525-4 IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma
    Print ISSN: 0950-9232
    Topics: Medicine
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  • 4
    Publication Date: 2018-01-10
    Description: We read with interest the article of recent advances in clinical practice of hepatocellular carcinoma (HCC) treatment by Bruix et al in Gut. 1 In this review, the Barcelona Clinic Liver Cancer (BCLC) Group recommended sorafenib as the standard treatment for BCLC-C stage (advanced stage) HCC. However, application of sorafenib as first treatment for advanced HCC worldwide was low according to a multiregional, large-scale, longitudinal cohort study. 2 This may be attributed to some limitations of sorafenib: low response rate, modest survival advantage, complex mechanism underlying acquired resistance and high-level heterogeneity of individual response. 3 4 Recently, evidence from an individual patient data meta-analysis of phase III randomised controlled trial showed no improvement in overall survival attributable to sorafenib for HBV-related HCC. 5 Therefore, more alternative strategies are highly required. 6 Hepatic arterial infusion (HAI) chemotherapy (HAIC) attracted more attentions in recent...
    Keywords: Gut
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 5
    Publication Date: 2018-02-09
    Description: There are no approved drugs for the treatment of heart failure with preserved ejection fraction (HFpEF), which is characterized by left ventricular (LV) diastolic dysfunction. We demonstrate that ITF2357 (givinostat), a clinical-stage inhibitor of histone deacetylase (HDAC) catalytic activity, is efficacious in two distinct murine models of diastolic dysfunction with preserved EF. ITF2357 blocked LV diastolic dysfunction due to hypertension in Dahl salt-sensitive (DSS) rats and suppressed aging-induced diastolic dysfunction in normotensive mice. HDAC inhibitor–mediated efficacy was not due to lowering blood pressure or inhibiting cellular and molecular events commonly associated with diastolic dysfunction, including cardiac fibrosis, cardiac hypertrophy, or changes in cardiac titin and myosin isoform expression. Instead, ex vivo studies revealed impairment of cardiac myofibril relaxation as a previously unrecognized, myocyte-autonomous mechanism for diastolic dysfunction, which can be ameliorated by HDAC inhibition. Translating these findings to humans, cardiac myofibrils from patients with diastolic dysfunction and preserved EF also exhibited compromised relaxation. These data suggest that agents such as HDAC inhibitors, which potentiate cardiac myofibril relaxation, hold promise for the treatment of HFpEF in humans.
    Print ISSN: 1946-6234
    Electronic ISSN: 1946-6242
    Topics: Medicine
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  • 6
    Publication Date: 2018-06-22
    Description: Borrelia burgdorferi , the agent of Lyme disease (LD), uses host-derived signals to modulate gene expression during the vector and mammalian phases of infection. Microarray analysis of mutants lacking the B orrelia host ad aptation r egulator (BadR) revealed the downregulation of genes encoding enzymes whose role in the pathophysiology of B. burgdorferi is unknown. Immunoblot analysis of the badR mutants confirmed reduced levels of these enzymes, and one of these enzymes, encoded by bb0086 , shares homology to prokaryotic magnesium chelatase and Lon-type proteases. The BB0086 levels in B. burgdorferi were higher under conditions mimicking those in fed ticks. Mutants lacking bb0086 had no apparent in vitro growth defect but were incapable of colonizing immunocompetent C3H/HeN or immunodeficient SCID mice. Immunoblot analysis revealed reduced levels of proteins critical for the adaptation of B. burgdorferi to the mammalian host, such as OspC, DbpA, and BBK32. Both RpoS and BosR, key regulators of gene expression in B. burgdorferi , were downregulated in the bb0086 mutants. Therefore, we designated BB0086 the B orrelia host ad aptation p rotein (BadP). Unlike badP mutants, the control strains established infection in C3H/HeN mice at 4 days postinfection, indicating an early colonization defect in mutants due to reduced levels of the lipoproteins/regulators critical for initial stages of infection. However, badP mutants survived within dialysis membrane chambers (DMCs) implanted within the rat peritoneal cavity but, unlike the control strains, did not display complete switching of OspA to OspC, suggesting incomplete adaptation to the mammalian phase of infection. These findings have opened a novel regulatory mechanism which impacts the virulence potential of B . burgdorferi .
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Allogeneic chimaeras that utilize C. B. 17 SCID mice (H-2d) as recipients of MHC mismatched bone marrow from C57B1/6(H-2nd) or SJL/J (H-2d) mice have been used to provide experimental evidence demonstrating the necessity for a direct interaction between an effector T helper and the cytotoxic T-cell precursor in order to generate cytotoxic effector T cells specific for the minor histocompatibility (H) antigens of DBA/2 (H) mice. No effect of helpers specific for antigen processed or not-presented on antigen-presenting cells could be observed. Allo-chimaeras that contain T cells hearing H-2d, and which are restricted to H-2d, make a cytotoxic T-cell response to minor H antigens which is H-2d restricted if, and only cloned anti-H-2d effector T helpers are present during the vivo printing step. Cloned anti-H-2d effector helpers, which are without effect in the allo-chimaeras, do provide a strong helper activity when tested in normal H-2d mice. These findings cannot reconciled with a strict single recognitive model of restrictive antigen recognition, but they are consistent with a dual recognitive model, which incorporates many of the features of the single recognitive model.
    Type of Medium: Electronic Resource
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2018-06-23
    Description: Lithium-ion batteries (LIBs) are considered to be one of the most important energy storage technologies. As the energy density of batteries increases, battery safety becomes even more critical if the energy is released unintentionally. Accidents related to fires and explosions of LIBs occur frequently worldwide. Some have caused serious threats to human life and health and have led to numerous product recalls by manufacturers. These incidents are reminders that safety is a prerequisite for batteries, and serious issues need to be resolved before the future application of high-energy battery systems. This Review aims to summarize the fundamentals of the origins of LIB safety issues and highlight recent key progress in materials design to improve LIB safety. We anticipate that this Review will inspire further improvement in battery safety, especially for emerging LIBs with high-energy density.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 9
    Publication Date: 2018-06-28
    Description: As national efforts to reduce CO 2 emissions intensify, policy-makers need increasingly specific, subnational information about the sources of CO 2 and the potential reductions and economic implications of different possible policies. This is particularly true in China, a large and economically diverse country that has rapidly industrialized and urbanized and that has pledged under the Paris Agreement that its emissions will peak by 2030. We present new, city-level estimates of CO 2 emissions for 182 Chinese cities, decomposed into 17 different fossil fuels, 46 socioeconomic sectors, and 7 industrial processes. We find that more affluent cities have systematically lower emissions per unit of gross domestic product (GDP), supported by imports from less affluent, industrial cities located nearby. In turn, clusters of industrial cities are supported by nearby centers of coal or oil extraction. Whereas policies directly targeting manufacturing and electric power infrastructure would drastically undermine the GDP of industrial cities, consumption-based policies might allow emission reductions to be subsidized by those with greater ability to pay. In particular, sector-based analysis of each city suggests that technological improvements could be a practical and effective means of reducing emissions while maintaining growth and the current economic structure and energy system. We explore city-level emission reductions under three scenarios of technological progress to show that substantial reductions (up to 31%) are possible by updating a disproportionately small fraction of existing infrastructure.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 10
    Publication Date: 2018-08-02
    Description: Pre-eclampsia is one of the main causes of perinatal mortality and morbidity. Many biomarkers for diagnosing pre-eclampsia have been found but most have low accuracy. Therefore, a potential marker that can detect pre-eclampsia with high accuracy is required. Infection has been reported as a cause of pre-eclampsia. In recent years, protein microarray chips have been recognized as a strong and robust tool for profiling antibodies for infection diagnoses. The purpose of the present study was to profile antibodies in the human plasma of healthy and pre-eclamptic pregnancies to identify suitable biomarkers. In this study, an Escherichia coli chip was probed with samples from 29 individuals (16 pre-eclamptic women and 13 healthy pregnant women) to profile plasma antibodies. Bioinformatics tools were used to analyze the results, discover conserved motifs, compare against the entire human proteome, and perform protein functional analysis. An antibody classifier was identified using k -top scoring pairs and additional samples for a blinded test were collected. The findings indicated that compared with the healthy women, the pre-eclamptic women exhibited 108 and 130 differentially immunogenic proteins against human immunoglobulins G and M, respectively. In addition, pre-eclamptic women developed more immunoglobulin G but less immunoglobulin M against bacterial surface proteins compared with healthy women. The k-top scoring pairs identified five pairs of immunogenic proteins as classifiers with a high accuracy of 90% in the blind test. [AG] [ISV] GV [AE] L [LF] and [IV] [IV] RI [AG] [AD] E were the consensus motifs observed in immunogenic proteins in the immunoglobulin G and immunoglobulin M of pre-eclamptic women, respectively, whereas GA [AG] [AL] L [LF] and [SRY] [IQML] [ILV] [ILV] [ACG] GI [GH] [AEF] [AK] [ATY] [RG] N [IV] were observed in the immunoglobulins G and immunoglobulin M of healthy women, respectively.
    Print ISSN: 1535-9476
    Electronic ISSN: 1535-9484
    Topics: Biology , Medicine
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