1,071 research outputs found

    Chemical markers to distinguish the homoand heterozygous bitter genotype in sweet almond kernels

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    Bitterness in almonds is controlled by a single gene (Sk dominant for sweet kernel, sk recessive for bitter kernel) and the proportions of the offspring genotypes (SkSk, Sksk, sksk) depend on the progenitors’ genotype. Currently, the latter is deduced after crossing by recording the phenotype of their descendants through kernel tasting. Chemical markers to early identify parental genotypes related to bitter traits can significantly enhance the efficiency of almond breeding programs. On this basis, volatile metabolites related to almond bitterness were investigated by Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry coupled to univariate and multivariate statistics on 244 homo- and heterozygous samples from 42 different cultivars. This study evidenced the association between sweet almonds’ genotype and some volatile metabolites, in particular benzaldehyde, and provided for the first time chemical markers to discriminate between homo- and heterozygous sweet almond genotypes. Furthermore, a multivariate approach based on independent variables was developed to increase the reliability of almond classification. The Partial Least Square-Discriminant Analysis classification model built with selected volatile metabolites that showed discrimination capacity allowed a 98.0% correct classification. The metabolites identified, in particular benzaldehyde, become suitable markers for the early genotype identification in almonds, while a DNA molecular marker is not yet available.info:eu-repo/semantics/publishedVersio

    Neutrophil Granulocytes in Ovarian Cancer - Induction of Epithelial-To- Mesenchymal-Transition and Tumor Cell Migration

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    Background: Ovarian cancer (OvCa) is a highly aggressive malignoma with a tumor-promoting microenvironment. Infiltration of polymorphonuclear neutrophils (PMN) is frequently seen, raising the question of their impact on tumor development. In that context, effects of PMN on human ovarian cancer cells were assessed. Methods: Human epithelial ovarian cancer cells were incubated with human PMN, lysate of PMN, or neutrophil elastase. Morphological alterations were observed by time-lapse video-microscopy, and the underlying molecular mechanism was analyzed by flow cytometry and Western blotting. Functional alternations were assessed by an in vitro wound healing assay. In parallel, a large cohort of n=334 primary OvCa tissue samples of various histological subtypes was histologically evaluated. Results: Co-cultivation of cancer cells with either PMN or PMN lysate causes a change of the polygonal epithelial phenotype of the cells towards a spindle shaped morphology, causing a cribriform cell growth. The PMN-induced alteration could be attributed to elastase, a major protease of PMN. Elastase-induced shape change was most likely due to the degradation of membranous E-cadherin, which results in loss of cell contacts and polarity. Moreover, in response to elastase, epithelial cytokeratins were downmodulated, in parallel with a nuclear translocation of β-catenin. These PMN-elastase induced alterations of cells are compatible with an epithelial-to-mesenchymal transition (EMT) of the cancer cells. Following EMT, the cells displayed a more migratory phenotype. In human biopsies, neutrophil infiltration was seen in 72% of the cases. PMN infiltrates were detected preferentially in areas with low E-cadherin expression. Conclusion: PMN in the microenvironment of OvCa can alter tumor cells towards a mesenchymal and migratory phenotype

    The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0

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    [1] The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999. The IBCAO bathymetric portrayals have since supported a wide range of Arctic science activities, for example, by providing constraint for ocean circulation models and the means to define and formulate hypotheses about the geologic origin of Arctic undersea features. IBCAO Version 3.0 represents the largest improvement since 1999 taking advantage of new data sets collected by the circum-Arctic nations, opportunistic data collected from fishing vessels, data acquired from US Navy submarines and from research ships of various nations. Built using an improved gridding algorithm, this new grid is on a 500 meter spacing, revealing much greater details of the Arctic seafloor than IBCAO Version 1.0 (2.5 km) and Version 2.0 (2.0 km). The area covered by multibeam surveys has increased from ∼6% in Version 2.0 to ∼11% in Version 3.0

    Second chances: Investigating athletes’ experiences of talent transfer

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    Talent transfer initiatives seek to transfer talented, mature individuals from one sport to another. Unfortunately talent transfer initiatives seem to lack an evidence-based direction and a rigorous exploration of the mechanisms underpinning the approach. The purpose of this exploratory study was to identify the factors which successfully transferring athletes cite as facilitative of talent transfer. In contrast to the anthropometric and performance variables that underpin current talent transfer initiatives, participants identified a range of psychobehavioral and environmental factors as key to successful transfer. We argue that further research into the mechanisms of talent transfer is needed in order to provide a strong evidence base for the methodologies employed in these initiatives

    Alpha-Decay in Isotopes of Atomic Number Less Than 83

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    Some time ago we started work in an attempt to observe alpha-particle decay in isotopes of atomic number less than 83. In the first experiments, thin targets of gold leaf were bombarded with 190-Mev deuterons in the 184-inch cyclotron. Two alpha-decay periods were observed in these targets; one of 0.7 minutes half-life and another of 4.3 minutes half-life. The alpha-particle energies were 5.7 and 5.2 Mev, respectively. Chemical separations proved that the 4.3-minute period is due to a gold isotope and suggested that the 0.7-minute period is due to a mercury isotope. The mass numbers of these new isotopes have not been determined. However, the results of excitation-functions in the production of the gold isotope by bombarding gold and platinum with protons suggest that its mass number lies in the range 185-188. The work on this isotope indicates that the alpha to electron capture branching ratio is of the order of magnitude of 10{sup -4}, and that positron activity accompanies the 4.3-minute alpha-period

    Ageing in the critical contact process: a Monte Carlo study

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    The long-time dynamics of the critical contact process which is brought suddenly out of an uncorrelated initial state undergoes ageing in close analogy with quenched magnetic systems. In particular, we show through Monte Carlo simulations in one and two dimensions and through mean-field theory that time-translation invariance is broken and that dynamical scaling holds. We find that the autocorrelation and autoresponse exponents lambda_{Gamma} and lambda_R are equal but, in contrast to systems relaxing to equilibrium, the ageing exponents a and b are distinct. A recent proposal to define a non-equilibrium temperature through the short-time limit of the fluctuation-dissipation ratio is therefore not applicable.Comment: 18 pages, 7 figures, Latex2e with IOP macros; final for

    The origin of human pathogenicity and biological interactions in Chaetothyriales

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    Fungi in the order Chaetothyriales are renowned for their ability to cause human infections. Nevertheless, they are not regarded as primary pathogens, but rather as opportunists with a natural habitat in the environment. Extremotolerance is a major trend in the order, but quite diferent from black yeasts in Capnodiales which focus on endurance, an important additional parameter is advancing toxin management. In the ancestral ecology of rock colonization, the association with metabolite-producing lichens is signifcant. Ant-association, dealing with pheromones and repellents, is another mainstay in the order. The phylogenetically derived family, Herpotrichiellaceae, shows dual ecology in monoaromatic hydrocarbon assimilation and the ability to cause disease in humans and cold-blooded vertebrates. In this study, data on ecology, phylogeny, and genomics were collected and analyzed in order to support this hypothesis on the evolutionary route of the species of Chaetothyriales. Comparing the ribosomal tree with that of enzymes involved in toluene degradation, a signifcant expansion of cytochromes is observed and the toluene catabolism is found to be complete in some of the Herpotrichiellaceae. This might enhance human systemic infection. However, since most species have to be traumatically inoculated in order to cause disease, their invasive potential is categorized as opportunism. Only in chromoblastomycosis, true pathogenicity might be surmised. The criterion would be the possible escape of agents of vertebrate disease from the host, enabling dispersal of adapted genotypes to subsequent generations.info:eu-repo/semantics/publishedVersio

    Broad targeting of resistance to apoptosis in cancer

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    Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

    The serotonin receptor 3E variant is a risk factor for female IBS-D

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    Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D

    Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study

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    <p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) is over-expressed in 70–75% of colorectal adenocarcinomas (CRC). The anti-EGFR monoclonal antibody cetuximab has been approved for the treatment of metastatic CRC, however tumor response to cetuximab has not been found to be associated with EGFR over-expression by immunohistochemistry (IHC). The aim of this study was to explore EGFR and the downstream effector phosphatase and tensin homologue deleted on chromosome 10 (PTEN) as potential predictors of response to cetuximab.</p> <p>Methods</p> <p>CRC patients treated with cetuximab by the Hellenic Cooperative Oncology group, whose formalin-fixed paraffin-embedded tumor tissue was available, were included. Tissue was tested for EGFR and PTEN by IHC and fluorescence in situ hybridization (FISH).</p> <p>Results</p> <p>Eighty-eight patients were identified and 72 were included based on the availability of tissue blocks with adequate material for analysis on them. All patients, except one, received cetuximab in combination with chemotherapy. Median follow-up was 53 months from diagnosis and 17 months from cetuximab initiation. At the time of the analysis 53% of the patients had died. Best response was complete response in one and partial response in 23 patients. In 16 patients disease stabilized. Lack of PTEN gene amplification was associated with more responses to cetuximab and longer time to progression (p = 0.042).</p> <p>Conclusion</p> <p>PTEN could be one of the molecular determinants of cetuximab response. Due to the heterogeneity of the population and the retrospective nature of the study, our results are hypothesis generating and should be approached with caution. Further prospective studies are needed to validate this finding.</p
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