66 research outputs found

    CONSTITUTIVE ACTIVATION OF THE RON GENE INDUCES INVASIVE GROWTH BUT NOT TRANSFORMATION

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    Bancos no consumo

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    Importantes alterações no ambiente regulatório brasileiro, somadas a uma tendência de redução de absorção do crédito pelo setor público, têm contribuído para uma ampliação dos produtos de crédito oferecidos à população. A corrida, no momento, é para capilarizar o crédito para consumidores fora do mercado bancário instituído. Para vencerem o desafio, os bancos, em um primeiro momento, buscaram força por meio de incorporações de financeiras; em um segundo momento estão indo, eles próprios, ao varejo, por meio de parcerias estratégicas com grandes redes varejistas

    Lung damage in SARS-CoV-2 patients: An autopsy study in the era of vaccination

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    Aims: The contribution of SARS-CoV-2 infection on lung damage and the effect of vaccination on either containing the number of deaths or mitigating lung damage has not been systematically investigated. Methods: Post-mortem analysis was performed among consecutive in-patients with COVID-19 deceased in the Province of Trieste (2020-2022). The outcomes of the study were (i) rates of in-hospital mortality, (ii) contribution of COVID-19 to death, (iii) histological extent of lung injury and (iv) impact of vaccination. Results: A total of 1038 consecutive hospitalized patients who died with SARS-CoV-2 infection were autopsied and deep histological analysis of the lungs was performed in a randomly selected sample of 508 cases. Among them, SARS-CoV-2 infection was (a) the cause of death (n = 90), (b) contributing to death (n = 304) and (c) an accompanying feature (n = 114). The incidence of SARS-CoV-2 infection as the primary cause of mortality decreased over time (23.8% in 2020, 20.9% in 2021 and 7.9% in 2022). On multivariable analysis, vaccination (any dose) was independently associated with lower rates of death related to SARS-CoV-2 infection (HR .15, p < .001), after adjusting for other independent predictors. A total of 172 patients were vaccinated at least with two doses at the time of death: 93% triple-vaccinated, 7% double-vaccinated. On histological analysis, vaccinated patients had a greater frequency of pneumonia severity score 0 and 1 (20.3% vs. 5.4% and 20.9% vs. 7.7%, p < .001, respectively), and a substantially lower proportion of pneumonia severity score 3 (26.2% vs. 55.1%, p < .001) compared to unvaccinated patients. Conclusions: COVID-19 vaccination has substantially reduced rates of death related to SARS-CoV-2 infection over time and may have the ability to mitigate lung damage

    Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder

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    Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic significance of RON and/or c-met protein (MET) expression was analysed in a bladder cancer cohort (n=183). There was no evidence of mutation in the kinase domain of RON. Overexpression of RON using an inducible Tet-off system induced increased cell proliferation, motility, and antiapoptosis. Immunohistochemical analysis showed that RON was overexpressed in 60 cases (32.8%) of primary tumours, with 14 (23.3%) showing a high level of expression. Recepteur d'Origine Nantais expression was positively associated with histological grading, larger size, nonpapillary contour, and tumour stage (all P<0.01). In addition, MET was overexpressed in 82 cases (44.8%). Co-expressed RON and MET was significantly associated with decreased overall survival (P=0.005) or metastasis-free survival (P=0.01) in 35 cases (19.1%). Recepteur d'Origine Nantais-associated signalling may play an important role in the progression of human bladder cancer. Evaluation of RON and MET expression status may identify a subset of bladder-cancer patients who require more intensive treatment

    Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high-throughput mutagenesis

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    Mutations causing aberrant splicing are frequently implicated in human diseases including cancer. Here, we establish a high-throughput screen of randomly mutated minigenes to decode the cis-regulatory landscape that determines alternative splicing of exon 11 in the proto-oncogene MST1R (RON). Mathematical modelling of splicing kinetics enables us to identify more than 1000 mutations affecting RON exon 11 skipping, which corresponds to the pathological isoform RON Delta 165. Importantly, the effects correlate with RON alternative splicing in cancer patients bearing the same mutations. Moreover, we highlight heterogeneous nuclear ribonucleoprotein H (HNRNPH) as a key regulator of RON splicing in healthy tissues and cancer. Using iCLIP and synergy analysis, we pinpoint the functionally most relevant HNRNPH binding sites and demonstrate how cooperative HNRNPH binding facilitates a splicing switch of RON exon 11. Our results thereby offer insights into splicing regulation and the impact of mutations on alternative splicing in cancer.Institute of Molecular Biology Core Facilities; DFG [ZA 881/2-1, KO 4566/4-1, LE 3473/2-1]; LOEWE program Ubiquitin Networks (Ub-Net) of the State of Hesse (Germany); Deutsche Forschungsgemeinschaft [SFB902 B13]; EMBO [3057]; Fundacao para a Ciencia e a Tecnologia, Portugal (FCT Investigator Starting Grant) [IF/00595/2014]; German Federal Ministry of Research (BMBF; e:bio junior group program) [FKZ: 0316196]; Boehringer Ingelheim Foundation; [INST 47/870-1 FUGG

    ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits

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    EMT and stemness: flexible processes tuned by alternative splicing in development and cancer progression

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    Kinetics of neuronal and endocrine secretion.

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