159 research outputs found

    Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1.

    Get PDF
    BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins.DOI: http://dx.doi.org/10.7554/eLife.02362.001

    Using Robotics to Support the Acquisition of STEM and 21st-Century Competencies: Promising (and Practical) Directions

    Get PDF
    To enhance how educators use robotics to support the development of STEM and 21st century competencies, we report findings from focus groups and interviews with 133 elementary teachers and 46 elementary students, 19 video-recorded classroom observations, and a teacher survey from Ontario, Canada. We find that teachers use robotics in a variety of ways to support the development of cognitive, interpersonal, and intrapersonal skills. Despite the potential benefits, our participants identified several factors that limit the adoption of robotics teaching and learning on a wider scale, including insufficient curriculum and assessment integration, resources, and professional development and support. We provide practical policy guidelines to support the broader integration of robotics and reflect on how these recommendations may inform teaching and learning in a (post-) COVID-19 classroom.Dans le but d’améliorer la façon dont les éducateurs utilisent la robotique pour soutenir le développement des compétences du XXIe siècle et des STIM, nous rapportons ici les résultats de groupes de discussion et d’entretiens individuels avec 133 enseignants et 46 élèves du primaire, de 19 observations de vidéos enregistrées en classe et d’un sondage auprès des enseignants effectué en Ontario, au Canada. Nous constatons que les enseignants utilisent la robotique de diverses manières pour soutenir le développement des compétences cognitives, interpersonnelles et intrapersonnelles. Malgré les avantages potentiels, nos participants ont identifié plusieurs facteurs qui limitent l’adoption de l’enseignement et de l’apprentissage de la robotique à plus grande échelle. Notamment, l’intégration insuffisante dans les curriculums et les évaluations, une pénurie de ressources, et un manque de développement et de soutien professionnel. Nous suggérons des directives politiques pratiques pour soutenir l’intégration plus efficace de la robotique, et considérons la manière dont ces recommandations pourraient éclairer l’enseignement et l’apprentissage dans une salle de classe (post) Covid-19

    Canadian K-12 Schooling During the COVID-19 Pandemic: Lessons and Reflections

    Get PDF
    The COVID-19 pandemic created an unprecedented disruption to education and schooling at the end of the 2019-20 school year. Operating in a context of great uncertainty, education leaders were tasked with making key decisions with potentially far-reaching impacts on the educational and mental and physical health of students and families. Drawing on 9 cross-sectoral focus groups with school board administrators, representatives from education industry partners, and K-12 educational policy research organizations, this paper provides a historical record of the evolution of decision-making and points to promising lines of inquiry and lessons that can be learned from this moment in education.

    Starting out in STEM : a study of young men and women in first year science, technology, engineering and mathematics courses

    Get PDF
    In late 2011, first year university students in science, technology, engineering and mathematics (STEM) courses across Australia were invited to participate in the international Interests and Recruitment in Science (IRIS) study. IRIS investigates the influences on young people\u27s decisions to choose university STEM courses and their subsequent experiences of these courses. The study also has a particular focus on the motivations and experiences of young women in courses such as physics, IT and engineering given the low rates of female participation in these fields. Around 3500 students from 30 Australian universities contributed their views on the relative importance of various school and non-school influences on their decisions, as well as insights into their experiences of university STEM courses so far. It is hoped that their contributions will help improve recruitment, retention and gender equity in STEM higher education and careers

    Editorial overview of Pearls Microbiome Series: E pluribus unum

    Get PDF
    The human microbiome constitutes the collection of all the microorganisms living in association with the human body with each body site being home to a unique microbial community. Human-associated microbial communities can include eukaryotes, archaea, bacteria, and viruses and provide protection against foreign invaders, stimulate the immune response, produce antimicrobials, and aid in digestion among other functions. Our understanding of the link between the human microbiome and disease is rapidly expanding in large part due to revolutionizing advances in next generation sequencing. In fact, an ever-growing number of studies have demonstrated that changes in the composition of our microbiomes correlate with numerous disease states or responses to treatment. However, understanding the impact of shifts in microbial communities on health and disease and the mechanisms that confer stability in the microbiome have been challenging to elucidate, due to the vast microbial diversity and differences between individuals. Nevertheless, the notion that manipulation of microbial communities may provide prophylactic or therapeutic tools to improve human health has been the focus of much research. Here, we highlight a collection of Pearls articles delving into the current state of knowledge linking the microbiome to human disease

    Candida dubliniensis Meningitis as Delayed Sequela of Treated C. dubliniensis Fungemia

    Get PDF
    We present a case of Candida dubliniensis meningitis that developed 2 months after apparently successful treatment of an episode of C. dubliniensis candidemia in a heart-lung transplant recipient in Australia. This case highlights the importance of follow-up in patients with candidemia or disseminated infection, especially in immunosuppressed patients

    Managing Monkeypox Virus Infections: A Contemporary Review

    Get PDF
    Monkeypox is an infectious and contagious zoonotic disease caused by the Orthopoxvirus species and was first identified in Africa. Recently, this infectious disease has spread widely in many parts of the world. Fever, fatigue, headache, and rash are common symptoms of monkeypox. The presence of lymphadenopathy is another prominent and key symptom of monkeypox, which distinguishes this disease from other diseases and is useful for diagnosing the disease. This disease is transmitted to humans through contact with or eating infected animals as well as objects infected with the virus. One of the ways to diagnose this disease is through PCR testing of lesions and secretions. To prevent the disease, vaccines such as JYNNEOS and ACAM2000 are available, but they are not accessible to all people in the world, and their effectiveness and safety need further investigation. However, preventive measures such as avoiding contact with people infected with the virus and using appropriate personal protective equipment are mandatory. The disease therapy is based on medicines such as brincidofovir, cidofovir, and Vaccinia Immune Globulin Intravenous. The injectable format of tecovirimat was approved recently, in May 2022. Considering the importance of clinical care in this disease, awareness about the side effects of medicines, nutrition, care for conjunctivitis, skin rash, washing and bathing at home, and so on can be useful in controlling and managing the disease

    Quantum Optics and Photonics

    Get PDF
    Contains reports on nine research projects.U.S. Air Force - Office of Scientific Research (Contract F49620-82-C-0091)U.S. Air Force - Rome Air Development CenterJoint Services Electronics Program (Contract DAAG29-83-K-0003)National Science Foundation Grant (Grant PHY 82-710369
    corecore