982 research outputs found

    Regulation of Reactive Oxygen Species and the Antioxidant Protein DJ-1 in Mastocytosis

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    Neoplastic accumulation of mast cells in systemic mastocytosis (SM) associates with activating mutations in the receptor tyrosine kinase KIT. Constitutive activation of tyrosine kinase oncogenes has been linked to imbalances in oxidant/antioxidant mechanisms in other myeloproliferative disorders. However, the impact of KIT mutations on the redox status in SM and the potential therapeutic implications are not well understood. Here, we examined the regulation of reactive oxygen species (ROS) and of the antioxidant protein DJ-1 (PARK-7), which increases with cancer progression and acts to lessen oxidative damage to malignant cells, in relationship with SM severity. ROS levels were increased in both indolent (ISM) and aggressive variants of the disease (ASM). However, while DJ-1 levels were reduced in ISM with lower mast cell burden, they rose in ISM with higher mast cell burden and were significantly elevated in patients with ASM. Studies on mast cell lines revealed that activating KIT mutations induced constant ROS production and consequent DJ-1 oxidation and degradation that could explain the reduced levels of DJ-1 in the ISM population, while IL-6, a cytokine that increases with disease severity, caused a counteracting transcriptional induction of DJ-1 which would protect malignant mast cells from oxidative damage. A mouse model of mastocytosis recapitulated the biphasic changes in DJ-1 and the escalating IL-6, ROS and DJ-1 levels as mast cells accumulate, findings which were reversed with anti-IL-6 receptor blocking antibody. Our findings provide evidence of increased ROS and a biphasic regulation of the antioxidant DJ-1 in variants of SM and implicate IL-6 in DJ-1 induction and expansion of mast cells with KIT mutations. We propose consideration of IL-6 blockade as a potential adjunctive therapy in the treatment of patients with advanced mastocytosis, as it would reduce DJ-1 levels making mutation-positive mast cells vulnerable to oxidative damage

    Plasticized poly(lactic acid) with low molecular weight poly(ethylene glycol) : mechanical, thermal, and morphology properties

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    Poly(lactic acid) PLA was plasticized with low molecular weight poly(ethylene glycol) PEG-200 to improve the ductility of PLA, while maintaining the plasticizer content at maximum 10 wt%. Low molecular weight of PEG enables increased miscibility with PLA and more efficient reduction of glass transition temperature (Tg). This effect is enhanced not only by the low molecular weight but also by its higher content. The tensile properties demonstrated that the addition of PEG-200 to PLA led to an increase of elongation at break (>7000%), but a decrease of both tensile strength and tensile modulus. The plasticization of the PLA with PEG-200 effectively lowers Tg as well as cold-crystallization temperature, increasing with plasticizer content. SEM micrographs reveal plastic deformation and few long threads of a deformed material are discernible on the fracture surface. The use of low molecular weight PEG-200 reduces the intermolecular force and increases the mobility of the polymeric chains, thereby improving the flexibility and plastic deformation of PLA

    Associations of sedentary behaviour, physical activity, blood pressure and anthropometric measures with cardiorespiratory fitness in children with cerebral palsy

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    Background - Children with cerebral palsy (CP) have poor cardiorespiratory fitness in comparison to their peers with typical development, which may be due to low levels of physical activity. Poor cardiorespiratory fitness may contribute to increased cardiometabolic risk. Purpose - The aim of this study was to determine the association between sedentary behaviour, physical activity and cardiorespiratory fitness in children with CP. An objective was to determine the association between cardiorespiratory fitness, anthropometric measures and blood pressure in children with CP. Methods- This study included 55 ambulatory children with CP [mean (SD) age 11.3 (0.2) yr, range 6-17 yr; Gross Motor Function Classification System (GMFCS) levels I and II]. Anthropometric measures (BMI, waist circumference and waist-height ratio) and blood pressure were taken. Cardiorespiratory fitness was measured using a 10 m shuttle run test. Children were classified as low, middle and high fitness according to level achieved on the test using reference curves. Physical activity was measured by accelerometry over 7 days. In addition to total activity, time in sedentary behaviour and light, moderate, vigorous, and sustained moderate-to-vigorous activity (≥10 min bouts) were calculated. Results - Multiple regression analyses revealed that vigorous activity (β = 0.339, p<0.01), sustained moderate-to-vigorous activity (β = 0.250, p<0.05) and total activity (β = 0.238, p<0.05) were associated with level achieved on the shuttle run test after adjustment for age, sex and GMFCS level. Children with high fitness spent more time in vigorous activity than children with middle fitness (p<0.05). Shuttle run test level was negatively associated with BMI (r2 = -0.451, p<0.01), waist circumference (r2 = -0.560, p<0.001), waist-height ratio (r2 = -0.560, p<0.001) and systolic blood pressure (r2 = -0.306, p<0.05) after adjustment for age, sex and GMFCS level. Conclusions - Participation in physical activity, particularly at a vigorous intensity, is associated with high cardiorespiratory fitness in children with CP. Low cardiorespiratory fitness is associated with increased cardiometabolic risk

    Employing a novel bioelastomer to toughen polylactide

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    Biodegradable, biocompatible polylactide (PLA) synthesized from renewable resources has attracted extensive interests over the past decades and holds great potential to replace many petroleum-derived plastics. With no loss of biodegradability and biocompatibility, we highly toughened PLA using a novel bioelastomer (BE)–synthesized from biomass diols and diacids. Although PLA and BE are immiscible, BE particles of ∼1 μm in diameter are uniformly dispersed in the matrix, and this indicates some compatibility between PLA and BE. BE significantly increased the cold crystallization ability of PLA, which was valuable for practical processing and performance. SEM micrographs of fracture surface showed a brittle-to-ductile transition owing to addition of BE. At 11.5 vol%, notched Izod impact strength improved from 2.4 to 10.3 kJ/m2, 330% increment; the increase is superior to previous toughening effect by using petroleum-based tougheners

    Food for Thought: Food, Embodiment, and Knowledge

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    The paradox of studying food is that scholars necessarily rely on the very instruments of discourse that reify a hierarchy of the senses designed to render food unworthy of serious thought: Images and texts appeal to the “higher” sense of sight; they “figure the material as intellectual, imaginative, symbolic, aesthetic,” Priscilla Parkhurst Ferguson claims (2004, 17). Reason cannot be found in the “lower” senses while eating reminds us too much of our body’s needs. But Krishnendu Ray reminds us that “much of the sociology of the body continues to be devoted to theoretical argumentation focussed on gender, sexuality, and disease, belying the sense that all social action {…} is always embodied” (2016, 26)

    Marked recent declines in boron in Baltic Sea cod otoliths – a bellwether of incipient acidification in a vast hypoxic system?

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    Ocean acidification is spreading globally as a result of anthropogenic CO2 emissions, but the Baltic Sea has until recently been thought to be relatively well-buffered by terrigenous inputs of alkalinity from its watershed. We discovered a 3- to 5-fold decline in boron (as B : Ca) in otoliths of eastern Baltic cod (EBC) between the late 1990s and 2021. Examining a time series of EBC otoliths, we found varying levels of B : Ca starting in the 1980s, with the most recent years showing an all-time low for this period. This trend correlates with declines in pH and dissolved oxygen but not with changes in salinity. We examined possible physiological influences on B : Ca by including a collection of Icelandic cod as an “out-group”. Icelandic cod otoliths showed strongly positive correlations of B : Ca with physiologically regulated P : Ca; this was not the case for EBC. Finally, B : Ca in EBC otoliths is negatively correlated, to some extent, with Mn : Mg, a proposed proxy for hypoxia exposure. This negative relationship is hypothesized to reflect the dual phenomena of hypoxia and acidification as a result of decomposition of large algal blooms. Taken together, the otolith biomarkers Mn : Mg and B : Ca in cod suggest a general increase in both hypoxia and acidification within the Baltic intermediate and deep waters in the last decade

    Compatible and crystallization properties of poly(lactic acid)/poly(butylenes adipate-co-terephthalate) blends

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    [[abstract]]Differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and dynamic mechanical analysis (DMA) properties of poly(lactic acid)/ poly(butylene adipate-co-terephthalate) (PLA/PBAT) specimens suggest that only small amounts of poor PLA and/or PBAT crystals are present in their corresponding melt crystallized specimens. In fact, the percentage crystallinity, peak melting temperature and onset re-crystallization temperature values of PLA/PBAT specimens reduce gradually as their PBAT contents increase. However, the glass transition temperatures of PLA molecules found by DSC and DMA analysis reduce to the minimum value as the PBAT contents of PLAxPBATy specimens reach 2.5 wt %. Further morphological and DMA analysis of PLA/PBAT specimens reveal that PBAT molecules are miscible with PLA molecules at PBAT contents equal to or less than 2.5 wt %, since no distinguished phase-separated PBAT droplets and tan δ transitions were found on fracture surfaces and tan δ curves of PLA/PBAT specimens, respectively. In contrast to PLA, the PBAT specimen exhibits highly deformable properties. After blending proper amounts of PBAT in PLA, the inherent brittle deformation behavior of PLA was successfully improved. Possible reasons accounting for these interesting crystallization, compatible and tensile properties of PLA/PBAT specimens are proposed.[[incitationindex]]SCI[[booktype]]紙
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