935 research outputs found

    Oxidative Stress and Parkinson’s Disease: Effects on Environmental Toxicology

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    Epidemiological studies have found an increased risk of Parkinson’s disease (PD) with environmental factors such as exposure to substances derived from industrial processes, use of agrochemicals, or living in a rural environment. The hypothesis that certain environmental toxins could be the source of the EP is supported by the discovery that chemicals such as herbicides paraquat, diquat, and the fungicide maneb are selectively toxic in nigrostriatal dopaminergic neurons. Also, one of the insecticides produced by plants, such as rotenone, and by-product of the synthesis of synthetic heroin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) can be reproduced in animal models where neurochemicals, histopathological, and clinical characteristic of PD can be found. Interestingly, there are similarities in the chemical structure of paraquat and MPTP. Recent evidence exhibited that inflammation and oxidative stress play an essential role in the development of PD. So, in our laboratory we found that in an animal model melatonin decreases the products of lipid oxidation, nitric oxide metabolites, and the activity of cyclooxygenase 2, which are induced by an intraperitoneal injection of MPTP. This suggests that the neuroprotective effects of melatonin are partially attributed to its antioxidant scavenging and anti-inflammatory action

    Protein diagenesis in "Patella" shells: Implications for amino acid racemisation dating

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    Abstract: The inter- and intra-crystalline fractions of Patella vulgata limpets recovered from archaeological sites in Northern Spain (covering Neolithic, Mesolithic, Magdalenian, Solutrean, and Aurignacian periods) were examined for amino acid composition and racemisation over time. The calcitic apex and rim areas of the shells were found to probably be composed of similar proteins, as the D/L values and amino acids were comparable and varied in the same way with increasing age; however, the mineral structures present in these areas differed. The aragonitic intermediate part of the shell showed a distinctly different amino acid composition and mineral structure. The main protein leaching from the inter-crystalline fraction occurred within the first 6000 yr after the death of the organism. In contrast, the intra-crystalline fraction d comprised of a different protein composition than the inter-crystalline fraction d appeared to behave as a closed system for at least 34 ka, as reflected by the lack of a significant decrease in the amino acid content; however, changes in the amino acid percentages occurred during this period. The concentration of aspartic acid remained almost constant with age both in inter- and intra-crystalline proteins, and its contribution to the total amino acid content increased with age at the expense of other amino acids such as glutamic acid, serine, glycine and alanine. Temperature is thought to play a key role in the amino acid racemisation of P. vulgata and could explain why in the localities belonging to the Gravettian and Solutrean period, which formed during relatively cold conditions, D/L values were similar to those detected in shells from sites formed during the Magdalenian.This paper was made possible by funding from the Spanish Ministry of Science and Innovation projects: HAR2010-22115-C02-01 “La respuesta humana al cambio climático global en una zona litoral: el caso del tránsito al Holoceno en la costa cantábrica (10000-5000 cal BC)”, and HAR2010-22115-C02-02 “Aplicación del análisis de sustancias orgánicas e inorgánicas a la reconstrucción paleoambiental, cronológica y tafonómica de yacimientos arqueológicos del Norte de España”

    Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia.

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    Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique expression of a variety of antigens, including the RNA helicase U5 snRNP200, on the surface of AML cells but not on normal hematopoietic precursors and skewed Fc receptor distribution in the AML immune microenvironment. Cell membrane localization of U5 snRNP200 was linked to surface expression of the Fcγ receptor IIIA (FcγIIIA, also known as CD32A) and correlated with expression of interferon-regulated immune response genes. Anti-U5 snRNP200 antibodies engaging activating Fcγ receptors were efficacious across immunocompetent AML models and were augmented by combination with azacitidine. These data provide a roadmap of AML-associated antigens with Fc receptor distribution in AML and highlight the potential for targeting the AML cell surface using Fc-optimized therapeutics

    Measurement of the Depth of Maximum of Extensive Air Showers above 10^18 eV

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    We describe the measurement of the depth of maximum, Xmax, of the longitudinal development of air showers induced by cosmic rays. Almost four thousand events above 10^18 eV observed by the fluorescence detector of the Pierre Auger Observatory in coincidence with at least one surface detector station are selected for the analysis. The average shower maximum was found to evolve with energy at a rate of (106 +35/-21) g/cm^2/decade below 10^(18.24 +/- 0.05) eV and (24 +/- 3) g/cm^2/decade above this energy. The measured shower-to-shower fluctuations decrease from about 55 to 26 g/cm^2. The interpretation of these results in terms of the cosmic ray mass composition is briefly discussed.Comment: Accepted for publication by PR
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