Infection with a Brazilian isolate of Zika virus generates RIG‐I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signalling

Zika virus (ZIKV) is a major public health concern in the Americas. We report that ZIKV infection and RNA extracted from ZIKV infected cells potently activated the induction of type I interferons (IFNs). This effect was fully dependent on the mitochondrial antiviral signalling protein (MAVS), implicating RIG‐I‐like receptors (RLRs) as upstream sensors of viral RNA. Indeed, RIG‐I and the related RNA sensor MDA5 contributed to type I IFN induction in response to RNA from infected cells. We found that ZIKV NS5 from a recent Brazilian isolate blocked type I IFN induction downstream of RLRs and also inhibited type I IFN receptor (IFNAR) signalling. We defined the ZIKV NS5 nuclear localization signal and report that NS5 nuclear localization was not required for inhibition of signalling downstream of IFNAR. Mechanistically, NS5 blocked IFNAR signalling by both leading to reduced levels of STAT2 and by blocking phosphorylation of STAT1, two transcription factors activated by type I IFNs. Taken together, our observations suggest that ZIKV infection induces a type I IFN response via RLRs and that ZIKV interferes with this response by blocking signalling downstream of RLRs and IFNAR

Clinical and epidemiological features of AIDS/tuberculosis comorbidity

Frente à importância da comorbidade AIDS/tuberculose no mundo e especialmente no Brasil, este estudo foi realizado para descrever os aspectos clínicos e epidemiológicos dos casos de comorbidade notificados pelo Serviço de Epidemiologia do Hospital das Clínicas of the Universidade de São Paulo identificados de 1989 à 1997. MÉTODOS: Foram utilizados bancos de dados contendo informações de todos os casos notificados de AIDS/tuberculose assistidos pelo hospital. RESULTADOS: Durante o período estudado, foram identificados 559 pacientes com a comorbidade. Os fatores de risco para AIDS incluiam principalmente contato heterossexual (38,9%), seguido por uso de drogas endovenosas (29,3%), e contato homossexual/bissexual (23,2%). Quanto aos aspectos clínicos, houve maiores índices de tuberculose extrapulmonar em comparação com tuberculose isoladamente. As unidades ambulatoriais mostraram aumento das notificações de AIDS durante o período. A descrição epidemiológica mostrou um declínio na relação masculino/feminino, predomínio do acometimento da faixa etária de 20 a 39 anos e de indivíduos com escolaridade menor que 8 anos de estudo, com baixa qualificação profissional. CONCLUSÃO: As altas taxas de casos de comorbidade AIDS/tuberculose indicam a necessidade de melhor atendimento desses pacientes, objetivando a detecção precoce da comorbidade. Tendo em vista as más condições sócio-econômicas da maioria da população deste hospital, uma melhor atenção visa ao aumento da aderência ao tratamento, e por consequência, menores custos sociais.Considering the relevance of AIDS/tuberculosis comorbidity worldwide, especially in Brazil, this study was developed to describe the clinical and epidemiological features of the comorbid cases identified from 1989 to 1997 by the epidemiology service of the Hospital das Clínicas of the Universidade de São Paulo. METHODS: Databases containing information on all identified AIDS/tuberculosis cases cared for at the hospital were used to gather information on comorbid cases. RESULTS: During the period, 559 patients were identified as presenting with AIDS/tuberculosis comorbidity. Risk behavior for AIDS was primarily heterosexual contact (38.9%), followed by intravenous drug use (29.3%) and homosexual/bisexual contact (23.2%). Regarding clinical features, there were higher rates of extrapulmonary tuberculosis when compared to tuberculosis without comorbidity. There was an increase in reporting of AIDS by ambulatory units during the period. Epidemiologically, there was a decrease in the male/female ratio, a predominance in the 20 to 39 year-old age group, and a majority of individuals who had less than 8 years of schooling and had low professional qualifications. CONCLUSIONS: High rates of AIDS/tuberculosis cases at our hospital indicate the need for better attention towards early detection of tuberculosis, especially in its extrapulmonary form. Since the population that attends this hospital tends to be of a lower socioeconomic status, better management of AIDS and tuberculosis is required to increase the rates of treatment adherence and thus lower the social costs

Liver transplantation for acute liver failure due to antitubercular drugs – a single-center experience

OBJECTIVES: Patients receiving treatment for tuberculosis are at risk of developing acute liver failure due to the hepatotoxicity of antitubercular drugs. We aimed to describe our experience with liver transplantation from deceased donors in this situation. METHODS: We identified patients undergoing transplantation for acute liver failure due to antitubercular drugs in our prospectively maintained database. RESULTS: Of 81 patients undergoing transplantation for acute liver failure, 8 cases were attributed to antitubercular drugs during the period of 2006-2016. Regarding the time of tuberculosis treatment until the onset of jaundice, patients were on antitubercular drugs for a mean of 64.7 days (21-155 days). The model for end-stage liver disease (MELD) score of patients ranged from 32 to 47 (median 38), and seven patients underwent transplantation under vasopressors. The 1-year survival was 50%. Three patients died during the week following transplantation due to septic shock (including a patient with acute liver failure due to hepatic/ disseminated tuberculosis), and the remaining patient died 2 months after transplantation due to pulmonary infection. There were 2 cases of mild rejection and 1 case of moderate rejection. Of the surviving patients, all were considered cured of tuberculosis after alternative drugs were given. CONCLUSION: Patients arrived very sick and displayed poor survival after deceased donor transplantation

Development of a Computational Framework for Big Data-Driven Prediction of Long-Term Bridge Performance and Traffic Flow

Consistent efforts with dense sensor deployment and data gathering processes for bridge big data have accumulated profound information regarding bridge performance, associated environments, and traffic flows. However, direct applications of bridge big data to long-term decision-making processes are hampered by big data-related challenges, including the immense size and volume of datasets, too many variables, heterogeneous data types, and, most importantly, missing data. The objective of this project was to develop a foundational computational framework that can facilitate data collection, data squashing, data merging, data curing, and, ultimately, data prediction. By using the framework, practitioners and researchers can learn from past data, predict various information regarding long-term bridge performance, and conduct data-driven efficient planning for bridge management and improvement. This research project developed and validated several computational tools for the aforementioned objectives. The programs include (1) a data-squashing tool that can shrink years-long bridge strain sensor data to manageable datasets, (2) a data-merging tool that can synchronize bridge strain sensor data and traffic flow sensor data, (3) a data-curing framework that can fill in arbitrarily missing data with statistically reliable values, and (4) a data-prediction tool that can accurately predict bridge and traffic data. In tandem, this project performed a foundational investigation into dense surface sensors, which will serve as a new data source in the near future. The resultant hybrid datasets, detailed manuals, and examples of all programs have been developed and are shared via web folders. The conclusion from this research was that the developed framework will serve practitioners and researchers as a powerful tool for making big data-driven predictions regarding the long-term behavior of bridges and relevant traffic information

Nothing about us, without us:A case study of a consumer-run organization by and for people on the autism spectrum in the Netherlands

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Draft genomes of two Artocarpus plants, jackfruit (A. heterophyllus) and breadfruit (A. altilis)

Two of the most economically important plants in the Artocarpus genus are jackfruit (A. heterophyllus Lam.) and breadfruit (A. altilis (Parkinson) Fosberg). Both species are long-lived trees that have been cultivated for thousands of years in their native regions. Today they are grown throughout tropical to subtropical areas as an important source of starch and other valuable nutrients. There are hundreds of breadfruit varieties that are native to Oceania, of which the most commonly distributed types are seedless triploids. Jackfruit is likely native to the Western Ghats of India and produces one of the largest tree-borne fruit structures (reaching up to 45 kg). To-date, there is limited genomic information for these two economically important species. Here, we generated 273 Gb and 227 Gb of raw data from jackfruit and breadfruit, respectively. The high-quality reads from jackfruit were assembled into 162,440 scaffolds totaling 982 Mb with 35,858 genes. Similarly, the breadfruit reads were assembled into 180,971 scaffolds totaling 833 Mb with 34,010 genes. A total of 2822 and 2034 expanded gene families were found in jackfruit and breadfruit, respectively, enriched in pathways including starch and sucrose metabolism, photosynthesis, and others. The copy number of several starch synthesis-related genes were found to be increased in jackfruit and breadfruit compared to closely-related species, and the tissue-specific expression might imply their sugar-rich and starch-rich characteristics. Overall, the publication of high-quality genomes for jackfruit and breadfruit provides information about their specific composition and the underlying genes involved in sugar and starch metabolism