931 research outputs found

    A portable electrochemiluminescence aptasensor for β-lactoglobulin detection

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    Cow’s milk allergy is one of the most common food allergies in children with a prevalence of around 2.5%. Milk contains several allergens; the main ones are caseins and β-lactoglobulin (β-LG). At regulatory level, β-LG is not explicitly named, but milk is included in the list of substances or products causing allergies or intolerances. Hence, the presence of β-LG can be a useful marker for determining the presence of milk in food. In this work, we present an aptasensor based on electrochemiluminescence (ECL) for the quantification of β-LG in real food matrices displaying integrated advantages consisting of high specificity, good sensitivity, portability, and cost effectiveness. The performance and applicability of this sensor were tested by analyzing a sample of skimmed milk and an oat-based drink proposed as a vegetable substitute for milk of animal origin. We obtained a linear correlation between the intensity of the signal and the concentration of β-LG standard solutions (y = x * 0.00653 + 1.038, R2 = 0.99). The limit of detection (LOD) and the limit of quantification (LOQ) were found to be 1.36 and 4.55 μg L−1, respectively. Graphical abstract: [Figure not available: see fulltext.

    Overlap Among States at Different Temperatures in the SK Model

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    We discuss the issue of temperature chaos in the Sherrington--Kirkpatrick spin glass mean field model. We numerically compute probability distributions of the overlap among (equilibrium) configurations at two different values of the temperature, both in the spin glass phase. The situation on our medium size systems is clearly non-chaotic, but a weak form of chaos could be emerging on very large lattices.Comment: 4 pages in aps format including 8 ps figures. Small change

    Do dairy farming systems differ in antimicrobial use?

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    The quantitative assessment of antimicrobial use (AMU) in food-producing animals contributes to the provision of essential information for developing relevant and effective policies to reduce use and to control antimicrobial resistance. Information on AMU is available mainly for intensive dairy farming systems and specialized high-yielding breeds. The aim of this study is to investigate AMU in different dairy farming systems by comparing the treatment incidence in mountain farms with specialized high-yield dairy breeds or with dual-purpose breeds raised for milk production to the treatment incidence in lowland farms with specialized high-yield dairy breeds or with dual-purpose breeds raised for milk production. Significant differences were found only between the overall treatment incidence, as well as the treatment incidence of highest-priority critically important antimicrobials for human medicine, in lowland farms with high-yielding breeds and mountain farms with dual-purpose breeds. Mountain farms have a generally lower milk production and smaller herd size than lowland farms, provide cows with access to pasture, and limit concentrates in the diet. These management practices and the use of local/dual-purpose breeds could reduce the risk of production diseases and the consequent need for AMU

    The dysregulation of OGT/OGA cycle mediates Tau and APP neuropathology in down syndrome

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    Protein O-GlcNAcylation is a nutrient-related post-translational modification that, since its discovery some 30 years ago, has been associated with the development of neurodegenerative diseases. As reported in Alzheimer’s disease (AD), flaws in the cerebral glucose uptake translate into reduced hexosamine biosynthetic pathway flux and subsequently lead to aberrant protein O-GlcNAcylation. Notably, the reduction of O-GlcNAcylated proteins involves also tau and APP, thus promoting their aberrant phosphorylation in AD brain and the onset of AD pathological markers. Down syndrome (DS) individuals are characterized by the early development of AD by the age of 60 and, although the two conditions present the same pathological hallmarks and share the alteration of many molecular mechanisms driving brain degeneration, no evidence has been sought on the implication of O-GlcNAcylation in DS pathology. Our study aimed to unravel for the first time the role of protein O-GlcNacylation in DS brain alterations positing the attention of potential trisomy-related mechanisms triggering the aberrant regulation of OGT/OGA cycle. We demonstrate the disruption of O-GlcNAcylation homeostasis, as an effect of altered OGT and OGA regulatory mechanism, and confirm the relevance of O-GlcNAcylation in the appearance of AD hallmarks in the brain of a murine model of DS. Furthermore, we provide evidence for the neuroprotective effects of brain-targeted OGA inhibition. Indeed, the rescue of OGA activity was able to restore protein O-GlcNAcylation, and reduce AD-related hallmarks and decreased protein nitration, possibly as effect of induced autophagy

    BVR-A deficiency leads to autophagy impairment through the dysregulation of AMPK/mTOR axis in the brain—Implications for neurodegeneration

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    Biliverdin reductase-A (BVR-A) impairment is associated with increased accumulation of oxidatively-damaged proteins along with the impairment of autophagy in the brain during neurodegenerative disorders. Reduced autophagy inhibits the clearance of misfolded proteins, which then form neurotoxic aggregates promoting neuronal death. The aim of our study was to clarify the role for BVR-A in the regulation of the mTOR/autophagy axis by evaluating age-associated changes (2, 6 and 11 months) in cerebral cortex samples collected from BVR-A knock-out (BVR-A−/−) and wild-type (WT) mice. Our results show that BVR-A deficiency leads to the accumulation of oxidatively-damaged proteins along with mTOR hyper-activation in the cortex. This process starts in juvenile mice and persists with aging. mTOR hyper-activation is associated with the impairment of autophagy as highlighted by reduced levels of Beclin-1, LC3β, LC3II/I ratio, Atg5–Atg12 complex and Atg7 in the cortex of BVR-A−/− mice. Furthermore, we have identified the dysregulation of AMP-activated protein kinase (AMPK) as a critical event driving mTOR hyper-activation in the absence of BVR-A. Overall, our results suggest that BVR-A is a new player in the regulation of autophagy, which may be targeted to arrive at novel therapeutics for diseases involving impaired autophagy

    Transition phase towards psoriatic arthritis: Clinical and ultrasonographic characterisation of psoriatic arthralgia

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    Objective Non-specific musculoskeletal pain is common in subjects destined to develop psoriatic arthritis (PsA). We evaluated psoriatic patients with arthralgia (PsOAr) compared with psoriasis alone (PsO) and healthy controls (HCs) using ultrasonography (US) to investigate the anatomical basis for joint symptoms in PsOAr and the link between these imaging findings and subsequent PsA transition. Methods A cross-sectional prevalence analysis of clinical and US abnormalities (including inflammatory and structural lesions) in PsOAr (n=61), PsO (n=57) and HCs (n=57) was performed, with subsequent prospective follow-up for PsA development. Results Tenosynovitis was the only significant sonographic feature that differed between PsOAr and PsO (29.5% vs 5.3%, p<0.001), although synovitis and enthesitis were numerically more frequent in PsOAr. Five patients in PsOAr and one in PsO group developed PsA, with an incidence rate of 109.2/1000 person-years in PsOAr vs 13.4/1000 person-years in PsO (p=0.03). Visual Analogue Scale pain, Health Assessment Questionnaire, joint tenderness and US active enthesitis were baseline variables associated with PsA development. Conclusion Tenosynovitis was associated with arthralgia in subjects with psoriasis. Baseline US evidence of enthesitis was associated with clinical PsA development in the longitudinal analysis. These findings are relevant for enriching for subjects at risk of imminent PsA development

    A single amino acid switch converts the sleeping beauty transposase into an efficient unidirectional excisionase with utility in stem cell reprogramming

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    The Sleeping Beauty (SB) transposon is an advanced tool for genetic engineering and a useful model to investigate cut-and-paste DNA transposition in vertebrate cells. Here, we identify novel SB transposase mutants that display efficient and canonical excision but practically unmeasurable genomic re-integration. Based on phylogenetic analyses, we establish compensating amino acid replacements that fully rescue the integration defect of these mutants, suggesting epistasis between these amino acid residues. We further show that the transposons excised by the exc(+)/int(-) transposase mutants form extrachromosomal circles that cannot undergo a further round of transposition, thereby representing dead-end products of the excision reaction. Finally, we demonstrate the utility of the exc(+)/int(-) transposase in cassette removal for the generation of reprogramming factor-free induced pluripotent stem cells. Lack of genomic integration and formation of transposon circles following excision is reminiscent of signal sequence removal during V(D)J recombination, and implies that cut-and-paste DNA transposition can be converted to a unidirectional process by a single amino acid change
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