577 research outputs found

    Synthesis, characterization, and catalytic properties of AlPO4-40, CoAPO-40, and ZnAPO-40

    Get PDF
    The experimental conditions leading to the synthesis of pure and highly crystalline AlPO,-40, CoAPO-40, and ZnAPO-40 have been optimized. Although the preparation of these phases is favored by the presence of TMA+ in the synthesis gel, these ions have not been found incorporated in the final AFR structures. All materials have been characterized by powder XRD, t.g./d.s.c., SEM, EDX, 13C, 27AI, and 3’P solid-state n.m.r., diffuse reflectance u.v.-vis spectroscopy, FTi.r., and catalytic tests using the n-t-xylene isomerization as a model reaction. This multitechnique approach provides strong evidence for the framework incorporation of cobalt and zinc. The acid sites generated by the framework insertion of cobalt and zinc are stronger than those generated by the incorporation of silicon

    A human polymorphism affects NEDD4L subcellular targeting by leading to two isoforms that contain or lack a C2 domain

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Ubiquitination serves multiple cellular functions, including proteasomal degradation and the control of stability, function, and intracellular localization of a wide variety of proteins. NEDD4L is a member of the HECT class of E3 ubiquitin ligases. A defining feature of NEDD4L protein isoforms is the presence or absence of an amino-terminal C2 domain, a class of subcellular, calcium-dependent targeting domains. We previously identified a common variant in human <it>NEDD4L </it>that generates isoforms that contain or lack a C2 domain.</p> <p>Results</p> <p>To address the potential functional significance of the <it>NEDD4L </it>common variant on NEDD4L subcellular localization, NEDD4L isoforms that either contained or lacked a C2 domain were tagged with enhanced green fluorescent protein, transfected into <it>Xenopus laevis </it>kidney epithelial cells, and imaged by performing confocal microscopy on live cells. We report that the presence or absence of this C2 domain exerts differential effects on the subcellular distribution of NEDD4L, the ability of C2 containing and lacking NEDD4L isoforms to mobilize in response to a calcium stimulus, and the intracellular transport of subunits of the NEDD4L substrate, ENaC. Furthermore, the ability of the C2-containing isoform to influence ÎČ-ENaC mobilization from intracellular pools involves the NEDD4L active site for ubiquitination. We propose a model to account for the potential impact of this common genetic variant on protein function at the cellular level.</p> <p>Conclusion</p> <p>NEDD4L isoforms that contain or lack a C2 domain target different intracellular locations. Additionally, whereas the C2-containing NEDD4L isoform is capable of shuttling between the plasma membrane and intracellular compartments in response to calcium stimulus the C2-lacking isoform can not. The C2-containing isoform differentially affects the mobilization of ENaC subunits from intracellular pools and this trafficking step requires NEDD4L ubiquitin ligase activity. This observation suggests a new mechanism for the requirement for the PY motif in cAMP-mediated exocytosis of ENaC. We have elucidated how a common genetic variant can underlie significant functional diversity in NEDD4L at the cellular level. We propose a model that describes how that functional variation may influence blood pressure. Moreover, our observations regarding differential function of the NEDD4L isoforms may impact other aspects of physiology that involve this ubiquitin ligase.</p

    Expression and subcellular localization of the bromodomain-containing protein 7 is a prognostic biomarker in breast cancer

    Get PDF
    Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family. Previous studies suggest that BRD7 is predominantly localized in the nucleus, wherein it functions as a transcriptional regulator. Several lines of evidence imply a tumour suppressor function for BRD7. However, the importance of BRD7 in the pathogenesis of breast cancer is not well understood. We have investigated the expression, CpG island methylation and subcellular localization of BRD7 in breast cancer cell lines and clinical cases and thereby assessed its prognostic significance by correlating with clinical-pathological features and time-dependent clinical outcomes. We show that nuclear exclusion of BRD7 occurs commonly in breast cancer and is strongly associated with cases expressing wild-type p53. Moreover, clinical outcomes are significantly less favourable in cases with nuclear exclusion or loss of expression than those in which there is nuclear expression of BRD7. Methylation of the CpG island of BRD7 increases in breast cancer relative to normal breast tissue, but there is not an obvious correlation between methylation and reduced expression or between methylation and clinical outcomes. Overall, our results suggest that nuclear exclusion, rather than transcriptional silencing, is a common mechanism by which the tumour suppressor function of wild-type p53 is inhibited in breast cancer, and show that BRD7 is a promising candidate biomarker in breast cancer

    Seasonal H1N1 2007 influenza virus infection is associated with elevated pre‐exposure antibody titers to the 2009 pandemic influenza A (H1N1) virus

    Get PDF
    AbstractThe new influenza strain detected in humans in April 2009 has caused the first influenza pandemic of the 21st century. A cross‐reactive antibody response, in which antibodies against seasonal H1N1 viruses neutralized the 2009 pandemic influenza A (H1N1) virus (2009 pH1N1), was detected among individuals aged >60 years. However, factors other than age associated with such a cross‐reactive antibody response are poorly documented. Our objective was to examine factors potentially associated with elevated pre‐exposure viro‐neutralization and hemagglutination‐inhibition antibody titers against the 2009 pH1N1. We also studied factors associated with antibody titers against the 2007 seasonal H1N1 virus. One hundred subjects participating in an influenza cohort were selected. Sera collected in 2008 were analysed using hemagglutination inhibition and viro‐neutralization assays for the 2009 pH1N1 virus and the 2007 seasonal H1N1 virus. Viro‐neutralization results were explored using a linear mixed‐effect model and hemagglutination‐inhibition results using linear‐regression models for interval‐censored data. Elevated antibody titers against 2009 pH1N1 were associated with seasonal 2007 H1N1 infection (viro‐neutralization, p 0.006; hemagglutination‐inhibition, p 0.018). Elevated antibody titers were also associated with age in the viro‐neutralization assay (p <0.0001). Seasonal 2007 H1N1 infection is an independent predictor of elevated pre‐exposure antibody titers against 2009 pH1N1 and may have contributed to lowering the burden of the 2009 pH1N1 pandemic

    Analysis of new control applications

    Get PDF
    This document reports the results of the activities performed during the first year of the CRUTIAL project, within the Work Package 1 "Identification and description of Control System Scenarios". It represents the outcome of the analysis of new control applications in the Power System and the identification of critical control system scenarios to be explored by the CRUTIAL project

    STUDY OF "BLOWN PACK" SPOILAGE OF CHILLED VACUUM PACKED BEEF

    Get PDF
    Blown pack spoilage of vacuum packed chilled beef was characterised by chemical (GCMS) analysis, microscope evaluation and microbiological analysis. Large amounts of butyric acid were found; the alteration was probably caused by psychrotrophic clostridia

    First diagnosis of multisystem inflammatory syndrome in children (MIS-C): an analysis of PoCUS findings in the ED

    Get PDF
    Children with multisystem inflammatory syndrome (MIS-C) tend to develop a clinical condition of fluid overload due both to contractile cardiac pump deficit and to endotheliitis with subsequent capillary leak syndrome. In this context, the ability of point-of-care ultrasound (PoCUS) to simultaneously explore multiple systems and detect polyserositis could promote adequate therapeutic management of fluid balance. We describe the PoCUS findings in a case-series of MIS-C patients admitted to the Emergency Department. At admission 10/11 patients showed satisfactory clinical condition without signs and symptoms suggestive for cardiovascular impairment/shock, but PoCUS showed pathological findings in 11/11 (100%). In particular, according to Rapid Ultrasound in SHock (RUSH) protocol, cardiac hypokinesis was detected in 5/11 (45%) and inferior vena cava dilatation in 3/11 (27%). Peritoneal fluid was reported in 6/11 cases (54%). Lung ultrasound (LUS) evaluation revealed an interstitial syndrome in 11/11 (100%), mainly localized in posterior basal lung segments. We suggest PoCUS as a useful tool in the first evaluation of children with suspected MIS-C for the initial therapeutic management and the following monitoring of possible cardiovascular deterioration

    Electrical Properties of Meso-Porous Silicon: from a surface effect to Coulomb Blockade and more

    Get PDF
    Abstract: since the Volker Lehmann&apos;s paper &quot;Resistivity of Porous Silicon: a surface effect&quot; published in 1995 [1], a great deal of efforts has been produced in understanding the basic mechanisms ruling the electron transport in Si mesostructures and how these phenomena are affected by external environment. After more than 10 years, new experimental evidences and physical insights have been obtained, like gas sensitivity [2], chemisorption phenomena [3], Coulomb blockade [4] and glassy dynamics In the first half of the &apos;90s, the most studied porous silicon morphology was from high resistivity p-type wafers, because of the high luminescence efficiency. The Lehmann&apos;s paper on electrical properties of porous silicon from p+ doped wafers, addressed few unanswered crucial questions regarding resistivity, impurity role, carrier freeze out and surface conditioning proposing a microscopic model of transport in mesoPS, in analogy to submicron channels of CMOS devices, whose figures of telegraph noise are affected by single charge trapping at the oxide-semiconductor interface. In 1999, the first report of strong interaction between mesoporous p+ silicon was announced in Strasbourg, EMRS by our group The successive years were so devoted to a fundamental study of mesoporous silicon in interaction with gas, by means of IR spectroscopy, ESR, NMR and ab-initio calculations Since the former paper of 1999 other groups contributed to study the phenomenon of NO 2 interaction with detailed papers on IR spectroscopy and Drude effect due to free carriers restored by nitrogen dioxid

    Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3

    Get PDF
    ABSTRACT In normal subjects the main form of circulating insulin-like growth factor (IGF) is the 150-kDa complex. This complex is formed by the IGF peptide, the acid-stable IGF-binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS). Experimental and clinical data have demonstrated that ALS is primarily under the control ofGHand plays a critical role in maintaining constant levels of circulating IGF-I. In this study we evaluated ALS, IGF-I, and IGFBP-1, -2, and -3 in 45 acromegalic patients in basal conditions and, in 37 of these, twice after surgical therapy compared with 100 age- and sex-matched control subjects to estimate their value as parameter of GH secretory state. The results demonstrated that in acromegaly before treatment all parameters (ALS, 523 6 26; IGF-I, 129 6 6; IGFBP-1, 0.7 6 0.1; IGFBP-3, 234 6 21; nmol/L; mean 6 SEM) but IGFBP-2 were significantly different (P , 0.0001) from those in healthy subjects (ALS, 281 6 4; IGF-I, 22 6 1; IGFBP-1, 1.6 6 0.1; IGFBP-3, 91 6 3). IGF-I was more sensitive (100%) than ALS (89%), and both were more predictive of disease status than IGFBP-3, in that 27% of the patients had IGFBP-3 levels within the normal range. Considering the ALS/ IGFBP-3 molar ratio, almost 55% of ALS circulated in a free form in active acromegaly. Before treatment, the IGF-I/IGFBPs (21122 1 23) molar ratio, which can be regarded as free, biologically active, IGF-I, was greatly increased (0.77 6 0.06; P , 0.0001) compared with that in control subjects (0.23 6 0.01). After surgery, all 10 patients with controlled disease showed normalization of ALS (100% sensitivity), whereas 9 of them had normal IGFBP-3; reevaluation after varying lengths of time showed all these parameters within the normal range. In the 27 patients with active disease, IGF-I and ALS were more predictive of disease status (91% and 83% negative predictive values, respectively) than IGFBP-3 (53%).The basal ALS concentration correlated only with IGFBP-3 (r 5 0.70; P , 0.001). In postsurgery samples (first control) a statistically significant (P , 0.001) correlation was found between mean GH values as well as minimum GH after oral glucose tolerance test and ALS (r 5 0.72 and 0.83, respectively), IGF-I (r 5 0.69 and 0.77), IGFBP-3 (r 5 0.50 and 0.72), and IGFBP-2 (r 5 20.36 and 20.63). Similarly, IGF-I, IGFBP-3, and ALS were positively correlated among themselves and negatively correlated with IGFBP-2 (P , 0.001). In conclusion, in the diagnosis of acromegaly, the measurement of total IGF-I appears to be the most sensitive parameter among the subunits of the 150K complex, and IGFBP-3 the least sensitive. For ALS, this subunit is quite sensitive and appears to be a useful parameter in reassessment after surgical treatment
    • 

    corecore