419 research outputs found

    OCCURRENCE OF SORGHUM AND JOHNSONGRASS DOWNY MILDEW IN PUERTO RICO

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    OCCURRENCE OF SORGHUM AND JOHNSONGRASS DOWNY MILDEW IN PUERTO RIC

    Prepulse inhibition predicts spatial working memory performance in the inbred Roman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: relevance for studying pre-attentive and cognitive anomalies in schizophrenia

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    Animal models of schizophrenia-relevant symptoms are increasingly important for progress in our understanding of the neurobiological basis of the disorder and for discovering novel and more specific treatments. Prepulse inhibition (PPI) and working memory, which are impaired in schizophrenic patients, are among the symptoms/processes modeled in those animal analogues. We have evaluated whether a genetically-selected rat model, the Roman high-avoidance inbred strain (RHA-I), displays PPI deficits as compared with its Roman low-avoidance (RLA-I) counterpart and the genetically heterogeneous NIH-HS rat stock. We have investigated whether PPI deficits predict spatial working memory impairments (in the Morris water maze; MWM) in these three rat types (Experiment 1), as well as in a separate sample of NIH-HS rats stratified according to their extreme (High, Medium, Low) PPI scores (Experiment 2). The results from Exp. 1 show that RHA-I rats display PPI and spatial working memory deficits compared to both RLA-I and NIH-HS rats. Likewise, in Exp. 2, “Low-PPI” NIH-HS rats present significantly impaired working memory with respect to “Medium-PPI” and “High-PPI” NIH-HS subgroups. Further support to these results comes from correlational, factorial and multiple regression analyses, which reveal that PPI is positively associated with spatial working memory performance. Conversely, cued learning in the MWM was not associated with PPI.Thus, using genetically-selected and genetically heterogeneous rats, the present study shows, for the first time, that PPI is a positive predictor of performance in a spatial working memory task. These results may have translational value for schizophrenia symptom research in humans, as they suggest that either by psychogenetic selection or by focusing on extreme PPI scores from a genetically heterogeneous rat stock, it is possible to detect a useful (perhaps “at risk”) phenotype to study cognitive anomalies linked to schizophrenia

    Epigenetic silencing of TGFBI confers resistance to trastuzumab in human breast cancer

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    Altres ajuts: This work was supported in part by La Marató de TV3 (20131530, TPuig), financial support was from the University of Girona (MPCUdG2016/036), and the University of Girona and La Caixa Foundation awarded S. Palomeras with a predoctoral grant.Background: Acquired resistance to trastuzumab is a major clinical problem in the treatment of HER2-positive (HER2+) breast cancer patients. The selection of trastuzumab-resistant patients is a great challenge of precision oncology. The aim of this study was to identify novel epigenetic biomarkers associated to trastuzumab resistance in HER2+ BC patients. Methods: We performed a genome-wide DNA methylation (450K array) and a transcriptomic analysis (RNA-Seq) comparing trastuzumab-sensitive (SK) and trastuzumab-resistant (SKTR) HER2+ human breast cancer cell models. The methylation and expression levels of candidate genes were validated by bisulfite pyrosequencing and qRT-PCR, respectively. Functional assays were conducted in the SK and SKTR models by gene silencing and overexpression. Methylation analysis in 24 HER2+ human BC samples with complete response or non-response to trastuzumab-based treatment was conducted by bisulfite pyrosequencing. Results: Epigenomic and transcriptomic analysis revealed the consistent hypermethylation and downregulation of TGFBI, CXCL2, and SLC38A1 genes in association with trastuzumab resistance. The DNA methylation and expression levels of these genes were validated in both sensitive and resistant models analyzed. Of the genes, TGFBI presented the highest hypermethylation-associated silencing both at the transcriptional and protein level. Ectopic expression of TGFBI in the SKTR model suggest an increased sensitivity to trastuzumab treatment. In primary tumors, TGFBI hypermethylation was significantly associated with trastuzumab resistance in HER2+ breast cancer patients. Conclusions: Our results suggest for the first time an association between the epigenetic silencing of TGFBI by DNA methylation and trastuzumab resistance in HER2+ cell models. These results provide the basis for further clinical studies to validate the hypermethylation of TGFBI promoter as a biomarker of trastuzumab resistance in HER2+ breast cancer patients

    SAT Modulo Linear Arithmetic for Solving Polynomial

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    Polynomial constraint solving plays a prominent role in several areas of hardware and software analysis and verification, e.g., termination proving, program invariant generation and hybrid system verification, to name a few. In this paper we propose a new method for solving non-linear constraints based on encoding the problem into an SMT problem considering only linear arithmetic. Unlike other existing methods, our method focuses on proving satisfiability of the constraints rather than on proving unsatisfiability, which is more relevant in several applications as we illustrate with several examples. Nevertheless, we also present new techniques based on the analysis of unsatisfiable cores that allow one to efficiently prove unsatisfiability too for a broad class of problems. The power of our approach is demonstrated by means of extensive experiments comparing our prototype with state-of-the-art tools on benchmarks taken both from the academic and the industrial world

    Effect of physical activity, nutritional education, and consumption of extra virgin olive oil on lipid, physiological and anthropometric profiles in a pediatric population

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    BACKGROUND. The aim of this study was to determine the effects of nutritional education and vigorous physical activity on health-related parameters. METHODS. The sample group consisted of 134 children from 5 rurally located schools. Participants were divided between 5 different experimental groups: control group (CG), physical activity group (PA), nutritional education group (NE), combined intervention group (PA+NE), and a combined intervention group with additional substitution of normally used oil for extra virgin olive oil (EVOO; PA+NE+EVOO). The intervention consisted of 60 minute sessions of physical activity held twice a week as well as nutritional education sessions held over 6 months. RESULTS. Students in the groups receiving physical activity reduced their fat percentage and increased their muscle mass post intervention. At post-test the lipid profile improved in all intervention groups. The proportion of macronutrients and dietary cholesterol improved in the groups receiving nutritional education. The post-test comparison showed significantly lower fat percentage, sum of skinfolds and waist circumference in NE relative to CG and PA relative to CG. Diastolic blood pressure and glycaemia were significantly lower in PA+NE+EVOO relative to CG. CONCLUSION. A school-based program consisting of nutritional education or nutritional education plus a physical activity program showed a positive effect on health-related parameters in children

    Understanding and modelling wildfire regimes: An ecological perspective

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    © 2021 The Author(s).Recent extreme wildfire seasons in several regions have been associated with exceptionally hot, dry conditions, made more probable by climate change. Much research has focused on extreme fire weather and its drivers, but natural wildfire regimes—and their interactions with human activities—are far from being comprehensively understood. There is a lack of clarity about the 'causes' of wildfire, and about how ecosystems could be managed for the co-existence of wildfire and people. We present evidence supporting an ecosystem-centred framework for improved understanding and modelling of wildfire. Wildfire has a long geological history and is a pervasive natural process in contemporary plant communities. In some biomes, wildfire would be more frequent without human settlement; in others they would be unchanged or less frequent. A world without fire would have greater forest cover, especially in present-day savannas. Many species would be missing, because fire regimes have co-evolved with plant traits that resist, adapt to or promote wildfire. Certain plant traits are favoured by different fire frequencies, and may be missing in ecosystems that are normally fire-free. For example, post-fire resprouting is more common among woody plants in high-frequency fire regimes than where fire is infrequent. The impact of habitat fragmentation on wildfire crucially depends on whether the ecosystem is fire-adapted. In normally fire-free ecosystems, fragmentation facilitates wildfire starts and is detrimental to biodiversity. In fire-adapted ecosystems, fragmentation inhibits fires from spreading and fire suppression is detrimental to biodiversity. This interpretation explains observed, counterintuitive patterns of spatial correlation between wildfire and potential ignition sources. Lightning correlates positively with burnt area only in open ecosystems with frequent fire. Human population correlates positively with burnt area only in densely forested regions. Models for vegetation-fire interactions must be informed by insights from fire ecology to make credible future projections in a changing climate.We gratefully acknowledge support from the Leverhulme Centre for Wildfires, Environment and Society, who organized the virtual mini-workshop which initiated the writing of this paper. RKN is supported by the Leverhulme Centre. SPH and YS acknowledge support from the ERC-funded project GC2.0 (Global Change 2.0: Unlocking the past for a clearer future, Grant Number 694481). ICP, KJB and ND acknowledge support from the ERC-funded project REALM (Re-inventing Ecosystem And Land-surface Models, Grant Number 787203). JCH acknowledges funding from the ERC project SCATAPNUT (Grant Number 681885). This work is a contribution to the LEMONTREE (Land Ecosystem Models based On New Theory, obseRvations and ExperimEnts) project, funded through the generosity of Eric and Wendy Schmidt by recommendation of the Schmidt Futures program (SPH, YS and ICP)

    Highly sensitive MLH1 methylation analysis in blood identifies a cancer patient with low-level mosaic MLH1 epimutation

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    Constitutional MLH1 methylation (epimutation) is a rare cause of Lynch syndrome. Low-level methylation (<= 10%) has occasionally been described. This study aimed to identify low-level constitutional MLH1 epimutations and determine its causal role in patients with MLH1-hypermethylated colorectal cancer. Eighteen patients with MLH1-hypermethylated colorectal tumors in whom MLH1 methylation was previously undetected in blood by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were screened for MLH1 methylation using highly sensitive MS-melting curve analysis (MS-MCA). Constitutional methylation was characterized by different approaches. MS-MCA identified one patient (5.6%) with low-level MLH1 methylation ( 1%) in blood and other normal tissues, which was confirmed by clonal bisulfite sequencing in blood. The patient had developed three clonally related gastrointestinal MLH1-methylated tumor lesions at 22, 24, and 25 years of age. The methylated region in normal tissues overlapped with that reported for other carriers of constitutional MLH1 epimutations. Low-level MLH1 methylation and reduced allelic expression were linked to the same genetic haplotype, whereas the opposite allele was lost in patient's tumors. Mutation screening of MLH1 and other hereditary cancer genes was negative. Herein, a highly sensitive MS-MCA-based approach has demonstrated its utility for the identification of low-level constitutional MLH1 epigenetic mosaicism. The eventual identification and characterization of additional cases will be critical to ascertain the cancer risks associated with constitutional MLH1 epigenetic mosaicism

    Corrigendum to: Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from EUROAPS registry

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    Rheumatology 2020;59:1306–1314. doi:https://doi.org/10.1093/rheumatology/kez419 In the original article, the affiliation of co-author Cecilia Beatrice Chighizola should have read: “Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano, IRCCS, Cusano Milanino, Milan, Italy”. These details have been corrected only in this corrigendum to preserve the published version of record
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