71 research outputs found
TRAF3 Is Required for NF-\u3baB Pathway Activation Mediated by HTLV Tax Proteins
Human T-cell leukemia viruses type 1 (HTLV-1) and type 2 (HTLV-2) share a common genome organization and expression strategy but have distinct pathological properties. HTLV-1 is the etiological agent of Adult T-cell Leukemia (ATL) and of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), whereas HTLV-2 does not cause hematological disorders and is only sporadically associated with cases of subacute myelopathy. Both HTLV genomes encode two regulatory proteins that play a pivotal role in pathogenesis: the transactivating Tax-1 and Tax-2 proteins and the antisense proteins HBZ and APH-2, respectively. We recently reported that Tax-1 and Tax-2 form complexes with the TNF-receptor associated factor 3, TRAF3, a negative regulator of the non-canonical NF-kappa B pathway. The NF-kappa B pathway is constitutively activated by the Tax proteins, whereas it is inhibited by HBZ and APH-2. The antagonistic effects of Tax and antisense proteins on NF-kappa B activation have not yet been fully clarified. Here, we investigated the effect of TRAF3 interaction with HTLV regulatory proteins and in particular its consequence on the subcellular distribution of the effector p65/RelA protein. We demonstrated that Tax-1 and Tax-2 efficiency on NF-kappa B activation is impaired in TRAF3 deficient cells obtained by CRISPR/Cas9 editing. We also found that APH-2 is more effective than HBZ in preventing Tax-dependent NF-kappa B activation. We further observed that TRAF3 co-localizes with Tax-2 and APH-2 in cytoplasmic complexes together with NF-kappa B essential modulator NEMO and TAB2, differently from HBZ and TRAF3. These results contribute to untangle the mechanism of NF-kappa B inhibition by HBZ and APH-2, highlighting the different role of the HTLV-1 and HTLV-2 regulatory proteins in the NF-kappa B activation
The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients
Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer,
but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma
telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome.
Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after
CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels
and total cell-free RNA were determined using real-time PCR.
Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT
levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction
model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with
detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI
1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels.
Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal
cancer patients who undergo neoadjuvant therapy
Data standardization of plant-pollinator interactions
Background: Animal pollination is an important ecosystem function and service, ensuring both the integrity of natural systems and human well-being. Although many knowledge shortfalls remain, some high-quality data sets on biological interactions are now available. The development and adoption of standards for biodiversity data and metadata has promoted great advances in biological data sharing and aggregation, supporting large-scale studies and science-based public policies. However, these standards are currently not suitable to fully support interaction data sharing. Results: Here we present a vocabulary of terms and a data model for sharing plant–pollinator interactions data based on the Darwin Core standard. The vocabulary introduces 48 new terms targeting several aspects of plant–pollinator interactions and can be used to capture information from different approaches and scales. Additionally, we provide solutions for data serialization using RDF, XML, and DwC-Archives and recommendations of existing controlled vocabularies for some of the terms. Our contribution supports open access to standardized data on plant–pollinator interactions. Conclusions: The adoption of the vocabulary would facilitate data sharing to support studies ranging from the spatial and temporal distribution of interactions to the taxonomic, phenological, functional, and phylogenetic aspects of plant–pollinator interactions. We expect to fill data and knowledge gaps, thus further enabling scientific research on the ecology and evolution of plant–pollinator communities, biodiversity conservation, ecosystem services, and the development of public policies. The proposed data model is flexible and can be adapted for sharing other types of interactions data by developing discipline-specific vocabularies of terms.Fil: Salim, JosĂ© A. Universidade de Sao Paulo; BrasilFil: Saraiva, Antonio M.. Universidade de Sao Paulo; BrasilFil: Zermoglio, Paula Florencia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Norte. Instituto de Investigaciones En Recursos Naturales, Agroecologia y Desarrollo Rural. - Universidad Nacional de Rio Negro. Instituto de Investigaciones En Recursos Naturales, Agroecologia y Desarrollo Rural.; ArgentinaFil: Agostini, Kayna. Universidade Federal do SĂŁo Carlos; BrasilFil: Wolowski, Marina. Universidade Federal de Alfenas; BrasilFil: Drucker, Debora P.. Empresa Brasileira de Pesquisa Agropecuaria (embrapa);Fil: Soares, Filipi M.. Universidade de Sao Paulo; BrasilFil: Bergamo, Pedro J.. Jardim Botânico do Rio de Janeiro; BrasilFil: Varassin, Isabela G.. Universidade Federal do Paraná; BrasilFil: Freitas, Leandro. Jardim Botânico do Rio de Janeiro; BrasilFil: MauĂ©s, Márcia M.. Empresa Brasileira de Pesquisa Agropecuaria (embrapa);Fil: Rech, Andre R.. Universidade Federal dos Vales do Jequitinhonha e Mucuri; BrasilFil: Veiga, Allan K.. Universidade de Sao Paulo; BrasilFil: Acosta, Andre L.. Instituto TecnolĂłgico Vale; BrasilFil: Araujo, AndrĂ©a C. Universidade Federal do Mato Grosso do Sul; BrasilFil: Nogueira, Anselmo. Universidad Federal do Abc; BrasilFil: Blochtein, Betina. Pontificia Universidade CatĂłlica do Rio Grande do Sul; BrasilFil: Freitas, Breno M.. Universidade Estadual do Ceará; BrasilFil: Albertini, Bruno C.. Universidade de Sao Paulo; BrasilFil: Maia Silva, Camila. Universidade Federal Rural Do Semi Arido; BrasilFil: Nunes, Carlos E. P.. University of Stirling; BrasilFil: Pires, Carmen S. S.. Empresa Brasileira de Pesquisa Agropecuaria (embrapa);Fil: Dos Santos, Charles F.. Pontificia Universidade CatĂłlica do Rio Grande do Sul; BrasilFil: Queiroz, Elisa P.. Universidade de Sao Paulo; BrasilFil: Cartolano, Etienne A.. Universidade de Sao Paulo; BrasilFil: de Oliveira, FavĂzia F. Universidade Federal da Bahia; BrasilFil: Amorim, Felipe W.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: FontĂşrbel, Francisco E.. Pontificia Universidad CatĂłlica de ValparaĂso; ChileFil: da Silva, Gleycon V.. MinistĂ©rio da CiĂŞncia, Tecnologia, Inovações. Instituto Nacional de Pesquisas da AmazĂ´nia; BrasilFil: Consolaro, HĂ©lder. Universidade Federal de CatalĂŁo; Brasi
In Vitro and In Vivo Human Herpesvirus 8 Infection of Placenta
Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women
Data standardization of plant–pollinator interactions
Background: Animal pollination is an important ecosystem function and service, ensuring both the integrity of natural systems
and human well-being. Although many knowledge shortfalls remain, some high-quality data sets on biological interactions are now
available. The development and adoption of standards for biodiversity data and metadata has promoted great advances in biological
data sharing and aggregation, supporting large-scale studies and science-based public policies. However, these standards are currently
not suitable to fully support interaction data sharing.
Results: Here we present a vocabulary of terms and a data model for sharing plant–pollinator interactions data based on the Darwin
Core standard. The vocabulary introduces 48 new terms targeting several aspects of plant–pollinator interactions and can be used to
capture information from different approaches and scales. Additionally, we provide solutions for data serialization using RDF, XML,
and DwC-Archives and recommendations of existing controlled vocabularies for some of the terms. Our contribution supports open
access to standardized data on plant–pollinator interactions.
Conclusions: The adoption of the vocabulary would facilitate data sharing to support studies ranging from the spatial and temporal
distribution of interactions to the taxonomic, phenological, functional, and phylogenetic aspects of plant–pollinator interactions. We
expect to fill data and knowledge gaps, thus further enabling scientific research on the ecology and evolution of plant–pollinator
communities, biodiversity conservation, ecosystem services, and the development of public policies. The proposed data model is
flexible and can be adapted for sharing other types of interactions data by developing discipline-specific vocabularies of termsinfo:eu-repo/semantics/publishedVersio
Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations
BACKGROUND:
The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting.
METHODS:
We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model.
RESULTS:
The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392).
CONCLUSION:
We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design
Low in‑hospital mortality rate in patients with COVID‑19 receiving thromboprophylaxis: data from the multicentre observational START‑COVID Register
Abstract
COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre,
Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in
the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate
was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years
Educomunicação, Transformação Social e Desenvolvimento Sustentável
Esta publicação apresenta os principais trabalhos dos GTs do II Congresso Internacional de Comunicação e Educação nos temas Transformação social, com os artigos que abordam principalmente Educomunicação e/ou MĂdia-Educação, no contexto de polĂticas de diversidade, inclusĂŁo e equidade; e, em Desenvolvimento Sustentável os artigos que abordam os avanços da relação comunicação/educação no contexto da educação ambiental e desenvolvimento sustentável
Demographic, clinical, and service-use characteristics related to the clinician’s recommendation to transition from child to adult mental health services
Purpose:
The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians’ advice to continue treatment at AMHS.
Methods:
Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians’ transition recommendations.
Results:
Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS.
Conclusion:
Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services
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