342 research outputs found

    A novel route to Pt-Bi2O3 composite thin films and their application in photo-reduction of water

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    A novel homoleptic bismuth(III) β-diketonate (dibenzoylmethane – dbm) complex [Bi(dbm)3]2 has been used as a precursor to thin films of crystalline β-Bi2O3, and hexachloroplatinic acid (H2PtCl6·6H2O) has been demonstrated as a suitable precursor for deposition of platinum nanoparticles, both deposited via aerosol-assisted chemical vapour deposition (AACVD). Thin films of Pt–Bi2O3 were co-deposited from a mixture of [Bi(dbm)3]2 and H2PtCl6·6H2O; the introduction of Pt particles into β-Bi2O3 causes hydrogen to be evolved during photolysis of water over the composite material, a property not found for Pt particles or β-Bi2O3 alone

    Recovery and resilience of tropical forests after disturbance

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    The time taken for forested tropical ecosystems to re-establish post-disturbance is of widespread interest. Yet to date there has been no comparative study across tropical biomes to determine rates of forest re-growth, and how they vary through space and time. Here we present results from a meta-analysis of palaeoecological records that use fossil pollen as a proxy for vegetation change over the past 20,000 years. A total of 283 forest disturbance and recovery events, reported in 71 studies, are identified across four tropical regions. Results indicate that forests in Central America and Africa generally recover faster from past disturbances than those in South America and Asia, as do forests exposed to natural large infrequent disturbances compared with post-climatic and human impacts. Results also demonstrate that increasing frequency of disturbance events at a site through time elevates recovery rates, indicating a degree of resilience in forests exposed to recurrent past disturbance

    The use of implantable cardioverter defibrillators in Iceland: a retrospective population based study

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    BACKGROUND: Indications for implantable cardioverter defibrillator (ICD) implantation have expanded considerably in recent years, resulting in steadily growing numbers of ICD recipients worldwide. The aim of this study was to review the overall experience with ICDs in Iceland. METHODS: This was a retrospective single centre study set at the University Hospital in Iceland. Data on all ICD implantations in Iceland from the first implantation in 1992 till the end of 2002 was reviewed. RESULTS: Sixty-two patients (71% male) received an ICD during this period. There was an increase in the number of implants by year and the number of new implants in 2001 and 2002 amounted to 56 and 38 per million, respectively. The mean age at implantation was 58 (+/-14) years. Forty patients (65%) had coronary artery disease. The most common indications for ICD implantation were cardiac arrest, 32 (52%) and another 26 (42%) had experienced ventricular tachycardia without cardiac arrest. The most common adverse event was inappropriate shocks. Twenty-eight patients (45%) received therapy from their ICDs, with the majority receiving appropriate therapy. Of the thirteen patients deceased before or during the study period, no case of sudden arrhythmic death was observed. CONCLUSION: This study shows that the experience with ICDs in Iceland is in most respects similar to other Western countries

    The spliceosome U2 snRNP factors promote genome stability through distinct mechanisms; transcription of repair factors and R-loop processing

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    Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive. Here we identify two distinct mechanisms of how spliceosome U2 snRNP factors contribute to genome stability. We show that the spliceosome maintains protein levels of essential repair factors, thus contributing to homologous recombination repair. In addition, real-time laser microirradiation analysis identified rapid recruitment of the U2 snRNP factor SNRPA1 to DNA-damage sites. Functional analysis of SNRPA1 revealed a more immediate and direct role in preventing R-loop-induced DNA damage. Our present study implies a complex interrelation between transcription, mRNA splicing and the DDR. Cells require rapid spatio-temporal coordination of these chromatin transactions to cope with various forms of genotoxic stress

    Differential Scanning Fluorometry Signatures as Indicators of Enzyme Inhibitor Mode of Action: Case Study of Glutathione S-Transferase

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    Differential scanning fluorometry (DSF), also referred to as fluorescence thermal shift, is emerging as a convenient method to evaluate the stabilizing effect of small molecules on proteins of interest. However, its use in the mechanism of action studies has received far less attention. Herein, the ability of DSF to report on inhibitor mode of action was evaluated using glutathione S-transferase (GST) as a model enzyme that utilizes two distinct substrates and is known to be subject to a range of inhibition modes. Detailed investigation of the propensity of small molecule inhibitors to protect GST from thermal denaturation revealed that compounds with different inhibition modes displayed distinct thermal shift signatures when tested in the presence or absence of the enzyme's native co-substrate glutathione (GSH). Glutathione-competitive inhibitors produced dose-dependent thermal shift trendlines that converged at high compound concentrations. Inhibitors acting via the formation of glutathione conjugates induced a very pronounced stabilizing effect toward the protein only when GSH was present. Lastly, compounds known to act as noncompetitive inhibitors exhibited parallel concentration-dependent trends. Similar effects were observed with human GST isozymes A1-1 and M1-1. The results illustrate the potential of DSF as a tool to differentiate diverse classes of inhibitors based on simple analysis of co-substrate dependency of protein stabilization

    Flow-to-fracture transition and pattern formation in a discontinuous shear thickening fluid

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    Recent theoretical and experimental work suggests a frictionless-frictional transition with increasing inter-particle pressure explains the extreme solid-like response of discontinuous shear thickening suspensions. However, analysis of macroscopic discontinuous shear thickening flow in geometries other than the standard rheometry tools remain scarce. Here we use a Hele-Shaw cell geometry to visualise gas-driven invasion patterns in discontinuous shear thickening cornstarch suspensions. We plot quantitative results from pattern analysis in a volume fraction-pressure phase diagram and explain them in context of rheological measurements. We observe three distinct pattern morphologies: viscous fingering, dendritic fracturing, and system-wide fracturing, which correspond to the same packing fraction ranges as weak shear thickening, discontinuous shear thickening, and shear-jammed regimes

    Urinary Aminopeptidase Activities as Early and Predictive Biomarkers of Renal Dysfunction in Cisplatin-Treated Rats

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    This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.This study was supported by a grant (R1/12/2010/66) from the University of Jaén with the participation of Caja Rural of Jaén, and from the Carlos III Health Institute of the Spanish Ministry of Health and Consumer Affairs (Red de Investigación Renal, REDinREN RD06/0016/0017 and RD07/0016/2008), “FEDER una manera de hacer Europa.

    Differential Interactions of the Autonomous Pathway RRM Proteins and Chromatin Regulators in the Silencing of Arabidopsis Targets

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    We have recently shown that two proteins containing RRM-type RNA-binding domains, FCA and FPA, originally identified through their role in flowering time control in Arabidopsis, silence transposons and other repeated sequences in the Arabidopsis genome. In flowering control, FCA and FPA function in the autonomous pathway with conserved chromatin regulators, the histone demethylase FLD and the MSI1-homologue FVE, a conserved WD-repeat protein found in many chromatin complexes. Here, we investigate how the RRM proteins interact genetically with these chromatin regulators at a range of loci in the Arabidopsis genome. We also investigate their interaction with the DNA methylation pathway. In several cases the RRM protein activity at least partially required a chromatin regulator to effect silencing. However, the interactions of the autonomous pathway components differed at each target analysed, most likely determined by certain properties of the target loci and/or other silencing pathways. We speculate that the RNA-binding proteins FCA and FPA function as part of a transcriptome surveillance mechanism linking RNA recognition with chromatin silencing mechanisms

    CD9 Tetraspanin Interacts with CD36 on the Surface of Macrophages: A Possible Regulatory Influence on Uptake of Oxidized Low Density Lipoprotein

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    CD36 is a type 2 scavenger receptor with multiple functions. CD36 binding to oxidized LDL triggers signaling cascades that are required for macrophage foam cell formation, but the mechanisms by which CD36 signals remain incompletely understood. Mass spectrometry analysis of anti-CD36 immuno-precipitates from macrophages identified the tetraspanin CD9 as a CD36 interacting protein. Western blot showed that CD9 was precipitated from mouse macrophages by anti-CD36 monoclonal antibody and CD36 was likewise precipitated by anti-CD9, confirming the mass spectrometry results. Macrophages from cd36 null mice were used to demonstrate specificity. Membrane associations of the two proteins on intact cells was analyzed by confocal immunofluorescence microscopy and by a novel cross linking assay that detects proteins in close proximity (<40 nm). Functional significance was determined by assessing lipid accumulation, foam cell formation and JNK activation in wt, cd9 null and cd36 null macrophages exposed to oxLDL. OxLDL uptake, lipid accumulation, foam cell formation, and JNK phosphorylation were partially impaired in cd9 null macrophages. The present study demonstrates that CD9 associates with CD36 on the macrophage surface and may participate in macrophage signaling in response to oxidized LDL
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