Susceptibility to blackheart disorder in potato tubers is influenced by sugar and phenolic profile

Blackheart (BH) is a physiological disorder of potato tubers in which internal tissue becomes discoloured during storage. The development of BH has been previously linked with general phenolic accumulation. In this study, five potato stocks cv. Maris Piper with different susceptibility to BH were selected across two consecutive seasons, whereupon targeted analysis of sugar and individual phenolic compounds in two tuber sections (flesh and heart) was conducted after storage at 1.5 °C or after one week at 15 °C. The most susceptible stock to BH had the highest accumulation of reducing sugars, while crypto- and neo-chlorogenic acids (chlorogenic acid isomers) were more abundant in flesh tissue of non-susceptible stocks. It is postulated that these metabolites may represent putative pre-symptomatic predictive biomarkers of stock susceptibility to BH

The chemopreventive retinoid 4HPR impairs prostate cancer cell migration and invasion by interfering with FAK/AKT/GSK3β pathway and β-catenin stability

<p>Abstract</p> <p>Background</p> <p>Prostate cancer shows an extremely slow progression, appearing in its metastatic, hormone refractory phenotype mostly in elderly men. The chemopreventive targeting of this tumor could accordingly delay its malignancy over life expectancy. The cancer chemopreventive retinoid <it>N</it>-(4 hydroxyphenyl)retinamide (4HPR) has already been shown to restrain prostate cancer growth in vitro and in vivo, though its mechanisms of action are only partially explained.</p> <p>Results</p> <p>We found that 4HPR impairs DU145 and PC3 prostate cancer cells migration and invasion by down-regulating FAK and AKT activation and by enhancing β-catenin degradation, causing the downregulation of target genes like cyclin D1, survivin and VEGF. This non-migratory phenotype was similarly produced in both cell lines by stable silencing of β-catenin. 4HPR was able to decrease AKT phosphorylation also when powerfully upregulated by IGF-1 and, consequently, to impair IGF-1-stimulated cell motility. Conversely, the expression of constitutively active AKT (myr-AKT) overcame the effects of 4HPR and β-catenin-silencing on cell migration. In addition, we found that BMP-2, a 4HPR target with antiangiogenic activity, decreased prostate cancer cell proliferation, migration and invasion by down-regulating the pathway described involving AKT phosphorylation, β-catenin stability and cyclin D1 expression.</p> <p>Conclusion</p> <p>These data point to 4HPR as a negative regulator of AKT phosphorylation, effectively targeting the β-catenin pathway and inducing a relatively benign phenotype in prostate cancer cells, limiting neoangiogenesis and cell invasion.</p

Assuring potato tuber quality during storage: A future perspective

Potatoes represent an important staple food crop across the planet. Yet, to maintain tuber quality and extend availability, there is a necessity to store tubers for long periods often using industrial-scale facilities. In this context, preserving potato quality is pivotal for the seed, fresh and processing sectors. The industry has always innovated and invested in improved post-harvest storage. However, the pace of technological change has and will continue to increase. For instance, more stringent legislation and changing consumer attitudes have driven renewed interest in creating alternative or complementary post-harvest treatments to traditional chemically reliant sprout suppression and disease control. Herein, the current knowledge on biochemical factors governing dormancy, the use of chlorpropham (CIPC) as well as existing and chemical alternatives, and the effects of pre- and post-harvest factors to assure potato tuber quality is reviewed. Additionally, the role of genomics as a future approach to potato quality improvement is discussed. Critically, and through a more industry targeted research, a better mechanistic understanding of how the pre-harvest environment influences tuber quality and the factors which govern dormancy transition should lead to a paradigm shift in how sustainable storage can be achieved

Effect of selenium enrichment on metabolism of tomato (Solanum lycopersicum) fruit during post‐harvest ripening

BACKGROUND Selenium (Se) enrichment of plants seems effective in enhancing the health‐related properties of produce, and in delaying plant senescence and fruit ripening. The current study investigated the effects of Se on tomato fruit ripening. Tomato (Solanum lycopersicum L.) plants were grown in hydroponics with different Se‐enriched nutrient solutions. Se, as sodium selenate, was added at rate of 0 mg L‐1 (control), 1 mg L‐1, and 1.5 mg L‐1. RESULTS Selenium was absorbed by roots and translocated to leaves and fruit. Se enrichment did not significantly affect the qualitative parameters of fruit at commercial harvest, instead it delayed ripening by affecting specific ripening‐related processes (respiration, ethylene production, color evolution) during postharvest. In the current experiment 100 g of tomato hydroponically grown with a 1.5 mg Se L‐1 enriched solution provided a total of 23.7 μg Se. Selenium recommended daily intake is 60 μg for women and 70 μg for men, thus the daily consumption of 100 g of enriched tomato would not lead to Se toxicity, but would provide a good Se diet supplementation. CONCLUSIONS The cultivation of tomato plants in a Se‐enriched solution appeared effective in producing tomato fruit with improved performances during storage and postharvest shelf life, and also with greater potential health‐promoting properties

Arginine : glycine amidinotransferase (AGAT) deficiency in a newborn: Early treatment can prevent phenotypic expression of the disease

Arginine:glycine amidinotransferase deficiency is a treatable inborn error of creatine synthesis, characterized by mental retardation, language impairment, and behavioral disorders. We describe a patient in whom arginine:glycine amidinotransferase was diagnosed at birth and treated at 4 months with creatine supplementation. In contrast with his 2 older sisters, he had normal psychomotor development at 18 months

Continuous exposure to ethylene differentially affects senescence in receptacle and achene tissues in strawberry fruit

Strawberry shelf life is limited, and little is known about the postharvest regulation of senescence in different fruit tissues. Strawberry is classified as a non-climacteric fruit, yet it is known that ethylene affects strawberry ripening. Here the effects of continuous exogenous ethylene (50 µl l−1) were investigated in cold stored strawberry (5°C). The physiological and biochemical responses of ripe strawberry were evaluated across 6 days, together with hormonal profiles of the whole fruit and individual tissues (achenes and receptacle). Continuous exposure to ethylene induced as a first response an accumulation of abscisic acid (ABA) in the receptacle tissue, followed by an increase in CO2 production. Ethylene also elicited sucrose hydrolysis and malic acid catabolism, with the major effect seen after 4 days of ethylene exposure. Additionally, accumulation of phenolics (epicatechin and chlorogenic acid) were also observed in ethylene treated strawberry. Achenes did not exhibit a response to ethylene, yet catabolism of both ABA and auxins increased by two thirds during air storage. In contrast, ethylene induced ABA accumulation in the receptacle tissue without ABA catabolism being affected. This hormonal disequilibrium in response to ethylene between the two tissues was maintained during storage, and therefore might be the precursor for the following biochemical variations reported during storag

Specific ADAM10 inhibitors localize in exosome-like vesicles released by Hodgkin lymphoma and stromal cells and prevent sheddase activity carried to bystander cells

Shedding of ADAM10 substrates, like TNFa, MICA or CD30, is reported to affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. Soluble forms of these molecules and ADAM10 can be carried and spread in the microenvironment by exosomes released by tumor cells. We reported new ADAM10 inhibitors able to prevent MICA shedding in Hodgkin lymphoma (HL), leading to recognition of HL cells by cytotoxic lymphocytes. In this paper, we show that the mature bioactive form of ADAM10 is released in exosome-like vesicles (ExoV) by HL cells and lymph node mesenchymal stromal cells (MSC). We demonstrate that ADAM10 inhibitors are released in ExoV by MSC or HL cells, endocytosed by bystander cells and localized in the endolysosomal compartment in HL MSC. ExoV released by HL cells can enhance MICA shedding by MSC, while ExoV from MSC induce TNFa or CD30 shedding by HL cells. Of note, ADAM10 sheddase activity carried by ExoV is prevented with the ADAM10 inhibitors LT4 and CAM29, pretreating either the ExoVproducing or the ExoV-receiving cells. In particular, both inhibitors reduce CD30 shedding maintaining the anti-tumor effects of the ADC Brentuximab-Vedotin or the anti-CD30 Iratumumab on HL cells. Thus, spreading of ADAM10 activity due to ExoV can result in the release of cytokines, like TNFa,a lymphoma growth factor, or soluble molecules, like sMICA or sCD30, that potentially interfere with host immune surveillance or immunotherapy. ADAM10 blockers can interfere with this process, allowing the development of anti-lymphoma immune response and/or efficient ADC-based or human antibody-based immunotherapy

ADAM10 new selective inhibitors reduce NKG2D ligand release sensitizing Hodgkin lymphoma cells to NKG2D-mediated killing

Hodgkin lymphoma (HL) resistant to conventional therapies is increasing, making of interest the search for new schemes of treatment. Members of the “A Disintegrin And Metalloproteases” (ADAMs) family, mainly ADAM10 or ADAM17, have been proposed as therapeutic targets in solid tumors and some ADAMs inhibitors have been shown to exert antitumor effects. We have previously described an overexpression of ADAM10 in HL, together with increased release of NKG2D ligands (NKG2D-L) and reduced activation of effector T lymphocytes with anti-lymphoma capacity. Aim of the present work was to verify whether inhibition of ADAM10 in HL cells could restore the triggering of NKG2D-dependent anti-lymphoma T cell response. As no selective ADAM10 blockers have been reported so far, we synthesized the two hydroxamate compounds LT4 and MN8 with selectivity for ADAM10 over metalloproteases (MMPs), LT4 showing higher specificity for ADAM10 over ADAM17. We show that (i) HL lymph nodes (LN) and cultured HL cells express high levels of the mature active membrane form of ADAM10; (ii) ADAM10 is the major sheddase for the NKG2D-L in HL cells; (iii) the new LT4 and MN8 compounds strongly reduce the shedding of NKG2D-L by HL cell lines and enhance the binding of NKG2D receptor; (iv) of note, these new ADAM10 inhibitors increase the sensitivity of HL cell lines to NKG2D-dependent cell killing exerted by natural killer and γδ T cells. Overall, the biologic activity of LT4 and MN8 appears to be more potent than that of the commercial inhibitor GI254023X

Assessing spleen stiffness by point shear‐wave elastography: Is it feasible and reproducible in patients with chronic liver disease? Is it useful to predict portal hypertension?

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Diagnostic accuracy of quantitative susceptibility mapping in multiple system atrophy: The impact of echo time and the potential of histogram analysis

The non-invasive quantification of iron stores via Quantitative Susceptibility Mapping (QSM) could play an important role in the diagnosis and the differential diagnosis of atypical Parkinsonisms. However, the susceptibility (χ) values measured via QSM depend on echo time (TE). This effect relates to the microstructural organization within the voxel, whose composition can be altered by the disease. Moreover, pathological iron deposition in a brain area may not be spatially uniform, and conventional Region of Interest (ROI)-based analysis may fail in detecting alterations. Therefore, in this work we evaluated the impact of echo time on the diagnostic accuracy of QSM on a population of patients with Multiple System Atrophy (MSA) of either Parkinsonian (MSAp) or cerebellar (MSAc) phenotypes. In addition, we tested the potential of histogram analysis to improve QSM classification accuracy. We enrolled 32 patients (19 MSAp and 13 MSAc) and 16 healthy controls, who underwent a 7T MRI session including a gradient-recalled multi-echo sequence for χ mapping. Nine histogram features were extracted from the χ maps computed for each TE in atlas-based ROIs covering deep brain nuclei, and compared among groups. Alterations of susceptibility distribution were found in the Putamen, Substantia Nigra, Globus Pallidus and Caudate Nucleus for MSAp and in the Substantia Nigra and Dentate Nucleus for MSAc. Increased iron deposition was observed in a larger number of ROIs for the two shortest TEs and the standard deviation, the 75th and the 90th percentile were the most informative features yielding excellent diagnostic accuracy with area under the ROC curve&nbsp;&gt;&nbsp;0.9. In conclusion, short TEs may enhance QSM diagnostic performances, as they can capture variations in rapidly-decaying contributions of high χ sources. The analysis of histogram features allowed to reveal fine heterogeneities in the spatial distribution of susceptibility alteration, otherwise undetected by a simple evaluation of ROI χ mean values