433 research outputs found

    Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis.

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    Barretts esophagus (BE) involves a metaplastic replacement of native esophageal squamous epithelium (Sq) by columnar-intestinalized mucosa, and it is the main risk factor for Barrett-related adenocarcinoma (BAc). Ultra-conserved regions (UCRs) are a class non-coding sequences that are conserved in humans, mice and rats. More than 90% of UCRs are transcribed (T-UCRs) in normal tissues, and are altered at transcriptional level in tumorigenesis. To identify the T-UCR profiles that are dysregulated in Barretts mucosa transformation, microarray analysis was performed on a discovery set of 51 macro-dissected samples obtained from 14 long-segment BE patients. Results were validated in an independent series of esophageal biopsy/surgery specimens and in two murine models of Barretts esophagus (i.e. esophagogastric-duodenal anastomosis). Progression from normal to BE to adenocarcinoma was each associated with specific and mutually exclusive T-UCR signatures that included up-regulation of uc.58-, uc.202-, uc.207-, and uc.223- and down-regulation of uc.214+. A 9 T-UCR signature characterized BE versus Sq (with the down-regulation of uc.161-, uc.165-, and uc.327-, and the up-regulation of uc.153-, uc.158-, uc.206-, uc.274-, uc.472-, and uc.473-). Analogous BE-specific T-UCR profiles were shared by human and murine lesions. This study is the first demonstration of a role for T-UCRs in the transformation of Barretts mucosa

    Mancha areolada de Thanatephorus da seringueira na Amazônia: identificação filogenética e variação genética em populações do patógeno.

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    A mancha areolada de Thanatephorus é uma das doenças mais importantes da seringueira (Hevea brasiliensis) na Amazônia. Apesar disso, questão importante sobre o real posicionamento filogenético deste patógeno ainda não foi respondida. Neste estudo, nós analisamos os padrões de variação genética em seqüências da região ITS-5.8S do rDNA de uma população de T. cucumeris (fase assexuada = Rhizoctonia solani AG 2-2) associado à mancha areolada da seringueira amostrada em Belém (Pará), Manaus (Amazonas) e Xapuri/Rio Branco (Acre) na Amazônia, e comparando-a filogeneticamente com membros do complexo AG 2 descritos mundialmente. Este estudo representa um passo importante para revelar a etiologia da fase assexuada de T.cucumeris da seringueira

    A cross-sectional study of SARS-CoV-2 seropositivity among healthcare workers and residents of long-term facilities in Italy, January 2021

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    Long‐term care facilities (LTCFs) are high‐risk settings for SARS‐CoV‐2 infection. This study aimed to describe SARS‐CoV‐2 seropositivity among residents of LTCFs and health‐care workers (HCWs). Subjects were recruited in January 2021 among unvaccinated HCWs of LTCFs and hospitals and residents of LTCFs in Northern Italy. Information concerning previous SARS‐CoV‐2 infections and a sample of peripheral blood were collected. Anti‐S SARS‐CoV‐2 IgG antibodies were measured using the EUROIMMUN Anti‐SARS‐CoV‐2 QuantiVac ELISA kit (EUROIMMUN Medizinische Labordiagnostika AG). For subjects with previous COVID‐19 infection, gender, age, type of subject (HCW or resident), and time between last positive swab and blood draw were considered as possible determinants of two outcomes: the probability to obtain a positive serological result and antibody titer. Six hundred and fifty‐eight subjects were enrolled. 56.1% of all subjects and 65% of residents presented positive results (overall median antibody titer: 31.0 RU/ml). Multivariable models identified a statistically significant 4% decrease in the estimated antibody level for each 30‐day increase from the last positive swab. HCWs were associated with significant odds for seroreversion over time (OR: 0.926 for every 30 days, 95% CI: 0.860–0.998), contrary to residents (OR: 1.059, 95% CI: 0.919–1.22). Age and gender were not factors predicting seropositivity over time. Residents could have a higher probability of maintaining a seropositive status over time compared to HCWs

    Asymmetric Fluid Criticality I: Scaling with Pressure Mixing

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    The thermodynamic behavior of a fluid near a vapor-liquid and, hence, asymmetric critical point is discussed within a general ``complete'' scaling theory incorporating pressure mixing in the nonlinear scaling fields as well as corrections to scaling. This theory allows for a Yang-Yang anomaly in which \mu_{\sigma}^{\prime\prime}(T), the second temperature derivative of the chemical potential along the phase boundary, diverges like the specific heat when T\to T_{\scriptsize c}; it also generates a leading singular term, |t|^{2\beta}, in the coexistence curve diameter, where t\equiv (T-T_{\scriptsize c}) /T_{\scriptsize c}. The behavior of various special loci, such as the critical isochore, the critical isotherm, the k-inflection loci, on which \chi^{(k)}\equiv \chi(\rho,T)/\rho^{k} (with \chi = \rho^{2} k_{\scriptsize B}TK_{T}) and C_{V}^{(k)}\equiv C_{V}(\rho,T)/\rho^{k} are maximal at fixed T, is carefully elucidated. These results are useful for analyzing simulations and experiments, since particular, nonuniversal values of k specify loci that approach the critical density most rapidly and reflect the pressure-mixing coefficient. Concrete illustrations are presented for the hard-core square-well fluid and for the restricted primitive model electrolyte. For comparison, a discussion of the classical (or Landau) theory is presented briefly and various interesting loci are determined explicitly and illustrated quantitatively for a van der Waals fluid.Comment: 21 pages in two-column format including 8 figure

    Impact of Mutation Density and Heterogeneity on Papillary Thyroid Cancer Clinical Features and Remission Probability

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    BACKGROUND: The need to integrate the classification of cancer with information on the genetic pattern has emerged in recent years for several tumors. METHODS: The genomic background of a large series of 208 papillary thyroid cancers (PTC) followed at a single center was analyzed by a custom MassARRAY genotyping platform, which allows the simultaneous detection of 19 common genetic alterations, including point mutations and fusions. RESULTS: Of the PTCs investigated, 71% were found to have pathognomonic genetic findings, with BRAFV600E and TERT promoter mutations being the most frequent monoallelic alterations (42% and 23.5%, respectively), followed by RET/PTC fusions. In 19.2% of cases, two or more point mutations were found, and the co-occurrence of a fusion with one or more point mutation(s) was also observed. Coexisting BRAFV600E and TERT promoter mutations were detected in a subgroup of aggressive PTCs (12%). A correlation between several aggressive features and mutation density was found, regardless of the type of association (i.e., only point mutations, or point mutations and fusions). Importantly, Kaplan-Meier curves demonstrated that mutation density significantly correlated with a higher risk of persistent disease. In most cases, the evaluation of the allelic frequencies normalized for the cancer cell content indicated the presence of the monoallelic mutation in virtually all tumor cells. A minority of cases was found to harbor low allelic frequencies, consistent with the presence of the mutations in a small subset of cancer cells, thus indicating tumor heterogeneity. Consistently, the presence of coexisting genetic alterations with different allelic frequencies in some tumors suggests that PTC can be formed by clones/subclones with different mutational profiles. CONCLUSIONS: A large mono-institutional series of PTCs was fully genotyped by means of a cost- and time-effective customized panel, revealing a strong impact of mutation density and genetic heterogeneity on the clinical features and on disease outcomes, indicating that an accurate risk stratification of thyroid cancer cannot rely on the analysis of a single genetic event. Finally, the heterogeneity found in some tumors warrants attention, since the occurrence of this phenomenon is likely to affect response to targeted therapies

    Aerobiology of the Wheat Blast Pathogen - Inoculum Monitoring and Detection of Fungicide Resistance Alleles

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    Wheat blast, caused by the ascomycetous fungus Pyricularia oryzae Triticum lineage (PoTl), is mainly controlled by fungicide use, but resistance to the main fungicide groups—sterol demethylase (DMI), quinone outside (QoI), and succinate dehydrogenase inhibitors (SDHI)—has been reported in Brazil. In order to rationalize fungicide inputs (e.g., choice, timing, dose-rate, spray number, and mixing/alternation) for managing wheat blast, we describe a new monitoring tool, enabling the quantitative measurement of pathogen’s inoculum levels and detection of fungicide resistance alleles. Wheat blast airborne spores (aerosol populations) were monitored at Londrina in Paraná State, a major wheat cropping region in Brazil, using an automated high-volume cyclone coupled with a lab-based quantitative real-time PCR (qPCR) assay. The objectives of our study were as follows: (1) to monitor the amount of PoTl airborne conidia during 2019–2021 based on DNA detection, (2) to reveal the prevalence of QoI resistant (QoI-R) cytochrome b alleles in aerosol populations of wheat blast, and (3) to determine the impact of weather on the dynamics of wheat blast aerosol populations and spread of QoI resistant alleles. PoTl inoculum was consistently detected in aerosols during the wheat cropping seasons from 2019 to 2021, but amounts varied significantly between seasons, with highest amounts detected in 2019. High peaks of PoTl DNA were also continuously detected during the off-season in 2020 and 2021. The prevalence of QoI resistant (QoI-R) cytochrome b G143A alleles in aerosol populations was also determined for a subset of 10 PoTl positive DNA samples with frequencies varying between 10 and 91% using a combination of PCR-amplification and SNP detection pyrosequencing. Statistically significant but low correlations were found between the levels of pathogen and the weather variables. In conclusion, for wheat blast, this system provided prior detection of airborne spore levels of the pathogen and of the prevalence of fungicide resistance alleles

    Identificação de leveduras isoladas de casos de mastite bovina por MALDI-TOF MS.

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    Multiplicação e avaliação do potencial de produção de sementes por híbridos de Brachiaria spp. em Campo Grande, MS.

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    O Brasil responde como maior produtor, consumidor e exportador de sementes de forrageiras tropicais, com produção anual estimada em mais de 150 mil toneladas. No início, a seleção de plantas forrageiras baseavase apenas no potencial de produção de massa e na qualidade da forragem. Porém, nos últimos anos, houve mudança nas linhas e estratégias nos programas de melhoramento, objetivando cultivares superiores em todos os aspectos, incluindo um dos mais importantes e limitantes, a produção de sementes. Nesse contexto, o objetivo deste trabalho será avaliar o potencial de produção de sementes de híbridos de Brachiaria, desenvolvidos e/ou pré-selecionados pelo programa de melhoramento genético do gênero da Embrapa Gado de Corte, para fins de seleção de genótipos superiores em produção de sementes, candidatos a novas cultivares ou potenciais genitores sexuais para serem utilizados em novos cruzamentos
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