292 research outputs found

    Smad3 promotes cancer progression by inhibiting E4BP4-mediated NK cell development

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    Ameliorative Effects of Neurolytic Celiac Plexus Block on Stress and Inflammation in Rats with Partial Hepatectomy

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    Purpose: To investigate effects of neurolytic celiac plexus block (NCPB) on stress and inflammation in rats with partial hepatectomy (PH).Methods: A model of PH rat was established, and serum C-reactive protein (CRP); corticosterone (GC); adrenocorticotropin (ACTH); noradrenaline (NA); adrenalin (AD); aspartate transaminase (AST); alanine transaminase (ALT); as well as tumor necrosis factor-α (TNF-α); interleukin (IL)-1β and IL-6; high mobility group box1 (HMGB1); and nitric oxide (NO) concentrations in serum assessed after PH. Additionally, Western blotting was performed to determine the effect of NCPB on expressions of glucocorticoid receptors (GR), inhibitor of nuclear factor kappa B (IκB), p65, c-Jun and inducible nitric oxide synthase (iNOS) of PH rats, as well as assay effects of NCPB on nuclear translocation of GR, c- Jun and p65. DNA binding activities of nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) were also determined.Results: NCPB reduced AST and ALT (P < 0.05), decreased secretion of inflammatory cytokines and NO (P < 0.05), as well as decreased CRP, GC, ACTH, NA and AD after PH (p < 0.05). NCPB increased expressions of GR and IκB, but expressions of p65, c-Jun, and iNOS (p < 0.05). Additionally, NCPB increased nuclear translocation of GR (p < 0.01), but decreased nuclear translocation of p65 and c-Jun after PH (p < 0.05). Additionally, DNA binding activity of NF-κB and AP-1 was decreased by NCPB (p < 0.05).Conclusion: The results indicate that NCPB treatment can significantly inhibit stress and inflammation in PH rats.Keywords: Neurolytic celiac plexus block, Cytokine, Nuclear translocation, Partial hepatectomy, Stress, Inflammatio

    A thermally erasable silicon oxide layer for molecular beam epitaxy

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    We present a systematic study of the oxidation and deoxidation behaviours of several kinds of ultrathin silicon oxide layers frequently used in silicon (Si) technology, which in this work serve as surface protecting layers for molecular beam epitaxy (MBE). With various characterization techniques, we demonstrate that a chemically grown silicon oxide layer is the most promising candidate for subsequent removal in an ultra-high vacuum chamber at a temperature of 1000 ∘C, without making use of a reducing agent. As a demonstration, a tensile-strained Ge(100) layer is epitaxially grown on the deoxidised wafer with an atomically flat surface and a low threading dislocation density of 3.33 × 108 cm−2. Our findings reveal that the ultra-thin oxide layer grown using a chemical approach is able to protect Si surfaces for subsequent MBE growth of Ge. This approach is promising for the growth of III/V-on-Si (using Ge as a buffer) and all group-IV related epitaxy for integration on the Si photonics platforms

    Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

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    The decay channel ψ′→π+π−J/ψ(J/ψ→γppˉ)\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) is studied using a sample of 1.06×1081.06\times 10^8 ψ′\psi^\prime events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the ppˉp\bar{p} invariant mass spectrum. The enhancement can be fit with an SS-wave Breit-Wigner resonance function with a resulting peak mass of M=1861−13+6(stat)−26+7(syst)MeV/c2M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2 and a narrow width that is Γ<38MeV/c2\Gamma<38 {\rm MeV/}c^2 at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

    Diverse Forms of RPS9 Splicing Are Part of an Evolving Autoregulatory Circuit

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    Ribosomal proteins are essential to life. While the functions of ribosomal protein-encoding genes (RPGs) are highly conserved, the evolution of their regulatory mechanisms is remarkably dynamic. In Saccharomyces cerevisiae, RPGs are unusual in that they are commonly present as two highly similar gene copies and in that they are over-represented among intron-containing genes. To investigate the role of introns in the regulation of RPG expression, we constructed 16 S. cerevisiae strains with precise deletions of RPG introns. We found that several yeast introns function to repress rather than to increase steady-state mRNA levels. Among these, the RPS9A and RPS9B introns were required for cross-regulation of the two paralogous gene copies, which is consistent with the duplication of an autoregulatory circuit. To test for similar intron function in animals, we performed an experimental test and comparative analyses for autoregulation among distantly related animal RPS9 orthologs. Overexpression of an exogenous RpS9 copy in Drosophila melanogaster S2 cells induced alternative splicing and degradation of the endogenous copy by nonsense-mediated decay (NMD). Also, analysis of expressed sequence tag data from distantly related animals, including Homo sapiens and Ciona intestinalis, revealed diverse alternatively-spliced RPS9 isoforms predicted to elicit NMD. We propose that multiple forms of splicing regulation among RPS9 orthologs from various eukaryotes operate analogously to translational repression of the alpha operon by S4, the distant prokaryotic ortholog. Thus, RPS9 orthologs appear to have independently evolved variations on a fundamental autoregulatory circuit

    Mechanism of cell death resulting from DNA interstrand cross-linking in mammalian cells

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    DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced cell death is unclear. Here, we show a novel mechanism of p53-independent apoptotic cell death involving prolonged cell-cycle (G2) arrest, ICL repair involving HR, transient mitosis, incomplete cytokinesis, and gross chromosomal abnormalities resulting from ICLs in mammalian cells. This characteristic ‘giant' cell death, observed by using time-lapse video microscopy, was reduced in ICL repair ERCC1- and XRCC3-deficient cells. Collectively, the results illustrate the coordination of ICL-induced cellular responses, including cell-cycle arrest, DNA damage repair, and cell death

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

    The Transcriptomes of Two Heritable Cell Types Illuminate the Circuit Governing Their Differentiation

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    The differentiation of cells into distinct cell types, each of which is heritable for many generations, underlies many biological phenomena. White and opaque cells of the fungal pathogen Candida albicans are two such heritable cell types, each thought to be adapted to unique niches within their human host. To systematically investigate their differences, we performed strand-specific, massively-parallel sequencing of RNA from C. albicans white and opaque cells. With these data we first annotated the C. albicans transcriptome, finding hundreds of novel differentially-expressed transcripts. Using the new annotation, we compared differences in transcript abundance between the two cell types with the genomic regions bound by a master regulator of the white-opaque switch (Wor1). We found that the revised transcriptional landscape considerably alters our understanding of the circuit governing differentiation. In particular, we can now resolve the poor concordance between binding of a master regulator and the differential expression of adjacent genes, a discrepancy observed in several other studies of cell differentiation. More than one third of the Wor1-bound differentially-expressed transcripts were previously unannotated, which explains the formerly puzzling presence of Wor1 at these positions along the genome. Many of these newly identified Wor1-regulated genes are non-coding and transcribed antisense to coding transcripts. We also find that 5′ and 3′ UTRs of mRNAs in the circuit are unusually long and that 5′ UTRs often differ in length between cell-types, suggesting UTRs encode important regulatory information and that use of alternative promoters is widespread. Further analysis revealed that the revised Wor1 circuit bears several striking similarities to the Oct4 circuit that specifies the pluripotency of mammalian embryonic stem cells. Additional characteristics shared with the Oct4 circuit suggest a set of general hallmarks characteristic of heritable differentiation states in eukaryotes

    Improved gradient descent algorithms for time-delay rational state-space systems: Intelligent search method and momentum method

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    This study proposes two improved gradient descent parameter estimation algorithms for rational state-space models with time-delay. These two algorithms, based on intelligent search method and momentum method, can simultaneously estimate the time-delay and parameters without the matrix eigenvalue calculation in each iteration. Compared with the traditional gradient descent algorithm, the improved algorithms come with two advantages: having quicker convergence rates and less computational efforts, particularly meaningful for those large scale systems. A simulated example is selected to illustrate the efficiency of the proposed algorithms
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