Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation

HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation

Taking the pulse of Earth's tropical forests using networks of highly distributed plots

Tropical forests are the most diverse and productive ecosystems on Earth. While better understanding of these forests is critical for our collective future, until quite recently efforts to measure and monitor them have been largely disconnected. Networking is essential to discover the answers to questions that transcend borders and the horizons of funding agencies. Here we show how a global community is responding to the challenges of tropical ecosystem research with diverse teams measuring forests tree-by-tree in thousands of long-term plots. We review the major scientific discoveries of this work and show how this process is changing tropical forest science. Our core approach involves linking long-term grassroots initiatives with standardized protocols and data management to generate robust scaled-up results. By connecting tropical researchers and elevating their status, our Social Research Network model recognises the key role of the data originator in scientific discovery. Conceived in 1999 with RAINFOR (South America), our permanent plot networks have been adapted to Africa (AfriTRON) and Southeast Asia (T-FORCES) and widely emulated worldwide. Now these multiple initiatives are integrated via ForestPlots.net cyber-infrastructure, linking colleagues from 54 countries across 24 plot networks. Collectively these are transforming understanding of tropical forests and their biospheric role. Together we have discovered how, where and why forest carbon and biodiversity are responding to climate change, and how they feedback on it. This long-term pan-tropical collaboration has revealed a large long-term carbon sink and its trends, as well as making clear which drivers are most important, which forest processes are affected, where they are changing, what the lags are, and the likely future responses of tropical forests as the climate continues to change. By leveraging a remarkably old technology, plot networks are sparking a very modern revolution in tropical forest science. In the future, humanity can benefit greatly by nurturing the grassroots communities now collectively capable of generating unique, long-term understanding of Earth's most precious forests. Resumen Los bosques tropicales son los ecosistemas más diversos y productivos del mundo y entender su funcionamiento es crítico para nuestro futuro colectivo. Sin embargo, hasta hace muy poco, los esfuerzos para medirlos y monitorearlos han estado muy desconectados. El trabajo en redes es esencial para descubrir las respuestas a preguntas que trascienden las fronteras y los plazos de las agencias de financiamiento. Aquí mostramos cómo una comunidad global está respondiendo a los desafíos de la investigación en ecosistemas tropicales a través de diversos equipos realizando mediciones árbol por árbol en miles de parcelas permanentes de largo plazo. Revisamos los descubrimientos más importantes de este trabajo y discutimos cómo este proceso está cambiando la ciencia relacionada a los bosques tropicales. El enfoque central de nuestro esfuerzo implica la conexión de iniciativas locales de largo plazo con protocolos estandarizados y manejo de datos para producir resultados que se puedan trasladar a múltiples escalas. Conectando investigadores tropicales, elevando su posición y estatus, nuestro modelo de Red Social de Investigación reconoce el rol fundamental que tienen, para el descubrimiento científico, quienes generan o producen los datos. Concebida en 1999 con RAINFOR (Suramérica), nuestras redes de parcelas permanentes han sido adaptadas en África (AfriTRON) y el sureste asiático (T-FORCES) y ampliamente replicadas en el mundo. Actualmente todas estas iniciativas están integradas a través de la ciber-infraestructura de ForestPlots.net, conectando colegas de 54 países en 24 redes diferentes de parcelas. Colectivamente, estas redes están transformando nuestro conocimiento sobre los bosques tropicales y el rol de éstos en la biósfera. Juntos hemos descubierto cómo, dónde y porqué el carbono y la biodiversidad de los bosques tropicales está respondiendo al cambio climático y cómo se retroalimentan. Esta colaboración pan-tropical de largo plazo ha expuesto un gran sumidero de carbono y sus tendencias, mostrando claramente cuáles son los factores más importantes, qué procesos se ven afectados, dónde ocurren los cambios, los tiempos de reacción y las probables respuestas futuras mientras el clima continúa cambiando. Apalancando lo que realmente es una tecnología antigua, las redes de parcelas están generando una verdadera y moderna revolución en la ciencia tropical. En el futuro, la humanidad puede beneficiarse enormemente si se nutren y cultivan comunidades de investigadores de base, actualmente con la capacidad de generar información única y de largo plazo para entender los que probablemente son los bosques más preciados de la tierra. Resumo Florestas tropicais são os ecossistemas mais diversos e produtivos da Terra. Embora uma boa compreensão destas florestas seja crucial para o nosso futuro coletivo, até muito recentemente os esforços de medições e monitoramento foram amplamente desconexos. É essencial formarmos redes para obtermos respostas que transcendem fronteiras e horizontes de agências financiadoras. Neste estudo nós mostramos como uma comunidade global está respondendo aos desafios da pesquisa de ecossistemas tropicais, com equipes diversas medindo florestas, árvore por árvore, em milhares de parcelas monitoradas à longo prazo. Nós revisamos as maiores descobertas científicas deste trabalho, e mostramos também como este processo está mudando a ciência de florestas tropicais. Nossa abordagem principal envolve unir iniciativas de base a protocolos padronizados e gerenciamento de dados a fim de gerar resultados robustos em escalas ampliadas. Ao conectar pesquisadores tropicais e elevar seus status, nosso modelo de Rede de Pesquisa Social reconhece o papel-chave do produtor dos dados na descoberta científica. Concebida em 1999 com o RAINFOR (América do Sul), nossa rede de parcelas permanentes foi adaptada para África (AfriTRON) e Sudeste asiático (T-FORCES), e tem sido extensamente reproduzida em todo o mundo. Agora estas múltiplas iniciativas estão integradas através de uma infraestrutura cibernética do ForestPlots.net, conectando colegas de 54 países de 24 redes de parcelas. Estas iniciativas estão transformando coletivamente o entendimento das florestas tropicais e seus papéis na biosfera. Juntos nós descobrimos como, onde e por que o carbono e a biodiversidade da floresta estão respondendo às mudanças climáticas, e seus efeitos de retroalimentação. Esta duradoura colaboração pantropical revelou um grande sumidouro de carbono persistente e suas tendências, assim como tem evidenciado quais direcionadores são mais importantes, quais processos florestais são mais afetados, onde eles estão mudando, seus atrasos no tempo de resposta, e as prováveis respostas das florestas tropicais conforme o clima continua a mudar. Dessa forma, aproveitando uma notável tecnologia antiga, redes de parcelas acendem faíscas de uma moderna revolução na ciência das florestas tropicais. No futuro a humanidade pode se beneficiar incentivando estas comunidades basais que agora são coletivamente capazes de gerar conhecimentos únicos e duradouros sobre as florestas mais preciosas da Terra. Résume Les forêts tropicales sont les écosystèmes les plus diversifiés et les plus productifs de la planète. Si une meilleure compréhension de ces forêts est essentielle pour notre avenir collectif, jusqu'à tout récemment, les efforts déployés pour les mesurer et les surveiller ont été largement déconnectés. La mise en réseau est essentielle pour découvrir les réponses à des questions qui dépassent les frontières et les horizons des organismes de financement. Nous montrons ici comment une communauté mondiale relève les défis de la recherche sur les écosystèmes tropicaux avec diverses équipes qui mesurent les forêts arbre après arbre dans de milliers de parcelles permanentes. Nous passons en revue les principales découvertes scientifiques de ces travaux et montrons comment ce processus modifie la science des forêts tropicales. Notre approche principale consiste à relier les initiatives de base à long terme à des protocoles standardisés et une gestion de données afin de générer des résultats solides à grande échelle. En reliant les chercheurs tropicaux et en élevant leur statut, notre modèle de réseau de recherche sociale reconnaît le rôle clé de l'auteur des données dans la découverte scientifique. Conçus en 1999 avec RAINFOR (Amérique du Sud), nos réseaux de parcelles permanentes ont été adaptés à l'Afrique (AfriTRON) et à l'Asie du Sud-Est (T-FORCES) et largement imités dans le monde entier. Ces multiples initiatives sont désormais intégrées via l'infrastructure ForestPlots.net, qui relie des collègues de 54 pays à travers 24 réseaux de parcelles. Ensemble, elles transforment la compréhension des forêts tropicales et de leur rôle biosphérique. Ensemble, nous avons découvert comment, où et pourquoi le carbone forestier et la biodiversité réagissent au changement climatique, et comment ils y réagissent. Cette collaboration pan-tropicale à long terme a révélé un important puits de carbone à long terme et ses tendances, tout en mettant en évidence les facteurs les plus importants, les processus forestiers qui sont affectés, les endroits où ils changent, les décalages et les réactions futures probables des forêts tropicales à mesure que le climat continue de changer. En tirant parti d'une technologie remarquablement ancienne, les réseaux de parcelles déclenchent une révolution très moderne dans la science des forêts tropicales. À l'avenir, l'humanité pourra grandement bénéficier du soutien des communautés de base qui sont maintenant collectivement capables de générer une compréhension unique et à long terme des forêts les plus précieuses de la Terre. Abstrak Hutan tropika adalah di antara ekosistem yang paling produktif dan mempunyai kepelbagaian biodiversiti yang tinggi di seluruh dunia. Walaupun pemahaman mengenai hutan tropika amat penting untuk masa depan kita, usaha-usaha untuk mengkaji dan mengawas hutah-hutan tersebut baru sekarang menjadi lebih diperhubungkan. Perangkaian adalah sangat penting untuk mencari jawapan kepada soalan-soalan yang menjangkaui sempadan dan batasan agensi pendanaan. Di sini kami menunjukkan bagaimana sebuah komuniti global bertindak balas terhadap cabaran penyelidikan ekosistem tropika melalui penglibatan pelbagai kumpulan yang mengukur hutan secara pokok demi pokok dalam beribu-ribu plot jangka panjang. Kami meninjau semula penemuan saintifik utama daripada kerja ini dan menunjukkan bagaimana proses ini sedang mengubah bidang sains hutan tropika. Teras pendekatan kami memberi tumpuan terhadap penghubungan inisiatif akar umbi jangka panjang dengan protokol standar serta pengurusan data untuk mendapatkan hasil skala besar yang kukuh. Dengan menghubungkan penyelidik-penyelidik tropika dan meningkatkan status mereka, model Rangkaian Penyelidikan Sosial kami mengiktiraf kepentingan peranan pengasas data dalam penemuan saintifik. Bermula dengan pengasasan RAINFOR (Amerika Selatan) pada tahun 1999, rangkaian-rangkaian plot kekal kami kemudian disesuaikan untuk Afrika (AfriTRON) dan Asia Tenggara (T-FORCES) dan selanjutnya telah banyak dicontohi di seluruh dunia. Kini, inisiatif-inisiatif tersebut disepadukan melalui infrastruktur siber ForestPlots.net yang menghubungkan rakan sekerja dari 54 negara di 24 buah rangkaian plot. Secara kolektif, rangkaian ini sedang mengubah pemahaman tentang hutan tropika dan peranannya dalam biosfera. Kami telah bekerjasama untuk menemukan bagaimana, di mana dan mengapa karbon serta biodiversiti hutan bertindak balas terhadap perubahan iklim dan juga bagaimana mereka saling bermaklum balas. Kolaborasi pan-tropika jangka panjang ini telah mendedahkan sebuah sinki karbon jangka panjang serta arah alirannya dan juga menjelaskan pemandu-pemandu perubahan yang terpenting, di mana dan bagaimana proses hutan terjejas, masa susul yang ada dan kemungkinan tindakbalas hutan tropika pada perubahan iklim secara berterusan di masa depan. Dengan memanfaatkan pendekatan lama, rangkaian plot sedang menyalakan revolusi yang amat moden dalam sains hutan tropika. Pada masa akan datang, manusia sejagat akan banyak mendapat manfaat jika memupuk komuniti-komuniti akar umbi yang kini berkemampuan secara kolektif menghasilkan pemahaman unik dan jangka panjang mengenai hutan-hutan yang paling berharga di dunia

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

IoT-based Smart Campus Monitoring Based on an Improved Chimp Optimization-Based Deep Belief Neural Network

Internet of Things (IoT) is a fast emerging technology that gained momentum steadily and shaped the future of the smart world. It has been created from the curiosity of human beings to provide comfortable and connected lifestyles with the mitigation of labor and therein promptly reduces the errors. This led to the usage of smart devices in everyday activities and thus enhances the efficacy of all smart applications. Smart applications include smart farming, healthcare, smart grid, smart city, and more. The application of IoT in monitoring the smart campus is an inevitable one to monitor the attendance of students and monitoring other activitieson the campus to protect the students and improve the education standards. Most education institutes use smart classrooms to achieve the aforementioned quality. Smart classrooms include audio-visual aids, multimedia, and smart boards along with these it is ineluctable to monitor the activities such as students’ attendance, analyzing the students-faculty performance, and content deliveries. To record the students’ attendance automatically we propose a Bluetooth-enabled IoT smart system for the positing of students with low energy utilization. The attendance can be recorded in the cloud environment by the Received signal strength indicator (RSSI). To achieve this we propose a novel IoT-based Deep Belief Neural Network (DBN) based Improved Chimp Optimization algorithm (ICO) for monitoring the attendance and positioning of the students’. An experimental study is conducted on Raspberry Pi with the deployment of Python and shows that our proposed approach provides better accuracy even with high interference signals