420 research outputs found

    Peptide transport by embryos of germinating barley (hordeum vulgare)

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    Two new fluorescent-labelling techniques for studying peptide transport are described. A peptide transport system has been demonstrated in a higher plant tissue, the scutellum of germinating barley embryos. This system has been extensively characterized, and found to have many similarities to peptide transport systems in microorganisms and mammalian tissues. Evidence has also been obtained for the existence of a peptide transport system in the membrane of an intracellular organelle, possibly the vacuole. Peptide transport is an active process and appears to require the production of a proton gradient across the plasmalemma. Disruption of the proton gradient not only inhibits peptide transport, but also causes general exodus of amino acids from the embryo and affects amino acid metabolism. Considerable pools of small peptides have been detected in both the endosperm and embryo of the germinating barley grain. The concentrations of peptides achieved in the endo sperm are of the right order of magnitude for the efficient operation of the peptide transport system. It seems that the uptake of small peptides by the scutellum of germinating barley embryos is of considerable importance in the transfer of nitrogen from the endosperm to the embryo during the iLobilization of zhe protein storage reserves

    The P2X(7 )receptor is a candidate product of murine and human lupus susceptibility loci: a hypothesis and comparison of murine allelic products

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    Systemic lupus erythematosus and its murine equivalent, modelled in the New Zealand Black and New Zealand White (NZB × NZW)F(1 )hybrid strain, are polygenic inflammatory diseases, probably reflecting an autoimmune response to debris from cells undergoing programmed cell death. Several human and murine loci contributing to disease have been defined. The present study asks whether the proinflammatory purinergic receptor P2X(7), an initiator of a form of programmed cell death known as aponecrosis, is a candidate product of murine and human lupus susceptibility loci. One such locus in (NZB × NZW)F(1 )mice is lbw3, which is situated at the distal end of NZW chromosome 5. We first assess whether NZB mice and NZW mice carry distinct alleles of the P2RX(7 )gene as expressed by common laboratory strains, which differ in sensitivity to ATP stimulation. We then compare the responses of NZB lymphocytes, NZW lymphocytes and (NZB × NZW)F(1 )lymphocytes to P2X(7 )stimulation. NZB and NZW parental strains express the distinct P2X(7)-L and P2X(7)-P alleles of P2RX(7), respectively, while lymphocytes from these and (NZB × NZW)F(1 )mice differ markedly in their responses to P2X(7 )receptor stimulation. NZB mice and NZW mice express functionally distinct alleles of the proinflammatory receptor, P2X(7). We show that current mapping suggests that murine and human P2RX(7 )receptor genes lie within lupus susceptibility loci lbw3 and SLEB4, and we argue that these encode a product with the functional characteristics consistent with a role in lupus. Furthermore, we argue that aponecrosis as induced by P2X(7 )is a cell death mechanism with characteristics that potentially have particular relevance to disease pathogenesis

    Gas-Diffusion Electrodes for Carbon-Dioxide Reduction: A New Paradigm

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    Significant advances have been made in recent years discovering new electrocatalysts and developing a fundamental understanding of electrochemical CO_2 reduction processes. This field has progressed to the point that efforts can now focus on translating this knowledge toward the development of practical CO_2 electrolyzers, which have the potential to replace conventional petrochemical processes as a sustainable route to produce fuels and chemicals. In this Perspective, we take a critical look at the progress in incorporating electrochemical CO_2 reduction catalysts into practical device architectures that operate using vapor-phase CO_2 reactants, thereby overcoming intrinsic limitations of aqueous-based systems. Performance comparison is made between state-of-the-art CO_2 electrolyzers and commercial H_2O electrolyzers—a well-established technology that provides realistic performance targets. Beyond just higher rates, vapor-fed reactors represent new paradigms for unprecedented control of local reaction conditions, and we provide a perspective on the challenges and opportunities for generating fundamental knowledge and achieving technological progress toward the development of practical CO_2 electrolyzers

    Gas-Diffusion Electrodes for Carbon-Dioxide Reduction: A New Paradigm

    Get PDF
    Significant advances have been made in recent years discovering new electrocatalysts and developing a fundamental understanding of electrochemical CO_2 reduction processes. This field has progressed to the point that efforts can now focus on translating this knowledge toward the development of practical CO_2 electrolyzers, which have the potential to replace conventional petrochemical processes as a sustainable route to produce fuels and chemicals. In this Perspective, we take a critical look at the progress in incorporating electrochemical CO_2 reduction catalysts into practical device architectures that operate using vapor-phase CO_2 reactants, thereby overcoming intrinsic limitations of aqueous-based systems. Performance comparison is made between state-of-the-art CO_2 electrolyzers and commercial H_2O electrolyzers—a well-established technology that provides realistic performance targets. Beyond just higher rates, vapor-fed reactors represent new paradigms for unprecedented control of local reaction conditions, and we provide a perspective on the challenges and opportunities for generating fundamental knowledge and achieving technological progress toward the development of practical CO_2 electrolyzers

    MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review

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    BACKGROUND: The DNA repair protein O6 methylguanine-DNA methyltransferase (MGMT) causes resistance of tumour cells to alkylating agents. It is a predictive biomarker in high grade gliomas treated with temozolomide, however there is no consensus on which test method, methylation sites, and cut-off values to use. METHODS: We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; where MGMT status was determined in tumour tissue, and assessed by one or more technique; and where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios. Two or more methods were compared in 32 independent cohorts with 3474 patients. RESULTS: Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP. CONCLUSIONS: We cannot draw strong conclusions about use of frozen tissue versus formalin-fixed paraffin embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and Pyrosequencing at CpG sites ranging from 72 to 95. A cut-off threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies. 190 studies were identified presenting hazard ratios from survival analysis in patients in which MGMT methylation was measured by one technique only

    Two novel missense mutations in ABCA1 result in altered trafficking and cause severe autosomal recessive HDL deficiency

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    AbstractExtremely low concentrations of high density lipoprotein (HDL)-cholesterol and apolipoprotein (apo) AI are features of Tangier disease caused by autosomal recessive mutations in ATP-binding cassette transporter A1 (ABCA1). Less deleterious, but dominantly inherited mutations cause HDL deficiency. We investigated causes of severe HDL deficiency in a 42-year-old female with progressive coronary disease.ApoAI-mediated efflux of cholesterol from the proband's fibroblasts was less than 10% of normal and nucleotide sequencing revealed inheritance of two novel mutations in ABCAI, V1704D and L1379F. ABCA1 mRNA was approximately 3-fold higher in the proband's cells than in control cells; preincubation with cholesterol increased it 5-fold in control and 8-fold in the proband's cells, but similar amounts of ABCA1 protein were present in control and mutant cells. When transiently transfected into HEK293 cells, confocal microscopy revealed that both mutant proteins were retained in the endoplasmic reticulum, while wild-type ABCA1 was located at the plasma membrane.Severe HDL deficiency in the proband was caused by two novel autosomal recessive mutations in ABCA1, one (V1704D) predicted to lie in a transmembrane segment and the other (L1379F) in a large extracellular loop. Both mutations prevent normal trafficking of ABCA1, thereby explaining their inability to mediate apoA1-dependent lipid efflux

    Caldera resurgence during the 2018 eruption of Sierra Negra volcano, Galápagos Islands.

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    Recent large basaltic eruptions began after only minor surface uplift and seismicity, and resulted in caldera subsidence. In contrast, some eruptions at Galápagos Island volcanoes are preceded by prolonged, large amplitude uplift and elevated seismicity. These systems also display long-term intra-caldera uplift, or resurgence. However, a scarcity of observations has obscured the mechanisms underpinning such behaviour. Here we combine a unique multiparametric dataset to show how the 2018 eruption of Sierra Negra contributed to caldera resurgence. Magma supply to a shallow reservoir drove 6.5 m of pre-eruptive uplift and seismicity over thirteen years, including an Mw5.4 earthquake that triggered the eruption. Although co-eruptive magma withdrawal resulted in 8.5 m of subsidence, net uplift of the inner-caldera on a trapdoor fault resulted in 1.5 m of permanent resurgence. These observations reveal the importance of intra-caldera faulting in affecting resurgence, and the mechanisms of eruption in the absence of well-developed rift systems
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