Routes and mechanisms of extracellular vesicle uptake

Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell-to-cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin-dependent endocytosis, and clathrin-independent pathways such as caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft-mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells

Carey Young’s 'Palais de Justice'

The symposium for this issue comprises six responses to the video artwork Palais de Justice (2017) by artist Carey Young. The video presents a study of the life of Brussels’ vast, late-nineteenth-century court building. In Palais de Justice, Young presents ‘a legal system seemingly centered on, and perhaps controlled by women’. The respondents are Jeanne Gaakeer, Ruth Herz, Joan Kee, Linda Mulcahy, Jeremy Pilcher and Gary Watt. Jeanne Gaakeer and Ruth Herz have the distinction of being, not only internationally respected scholars, but also experienced judges. Jeanne Gaakeer is a judge practicing in the Netherlands and Ruth Herz was formerly a judge in Germany. The six responses are followed by the artist’s own reflections on her artwork and her response to the commentators’ responses. Joan Kee writes that ‘Young highlights access as a key entry point for thinking about the law. Who can avail themselves of the law? Who may enter (or exit) the courts? Who is excluded and by whose authority? The surreptitious looking and peering that define the experience of watching the film suggests how these questions deny ready answers’

Medical Optimization Network for Space Telemedicine Resources

INTRODUCTION: Long-duration missions beyond low Earth orbit introduce new constraints to the space medical system. Beyond the traditional limitations in mass, power, and volume, consideration must be given to other factors such as the inability to evacuate to Earth, communication delays, and limitations in clinical skillsets. As NASA develops the medical system for an exploration mission, it must have an ability to evaluate the trade space of what resources will be most important. The Medical Optimization Network for Space Telemedicine Resources (MONSTR) was developed over the past year for this reason, and is now a system for managing data pertaining to medical resources and their relative importance when addressing medical conditions. METHODS: The MONSTR web application with a Microsoft SQL database backend was developed and made accessible to Tableau v9.3 for analysis and visualization. The database was initially populated with a list of medical conditions of concern for an exploration mission taken from the Integrated Medical Model (IMM), a probabilistic model designed to quantify in-flight medical risk. A team of physicians working within the Exploration Medical Capability Element of NASA's Human Research Program compiled a list diagnostic and treatment medical resources required to address best- and worst-case scenarios of each medical condition using a terrestrial standard of care and entered this data into the system. This list included both tangible resources (e.g. medical equipment, medications) and intangible resources (e.g. clinical skills required to perform a procedure). The physician team then assigned criticality values to each instance of a resource, representing the importance of that resource to diagnosing or treating its associated condition(s). Medical condition probabilities of occurrence during a Mars mission were pulled from the IMM and imported into the MONSTR database for use within a resource criticality-weighting algorithm. DISCUSSION: The MONSTR tool is a novel approach to assess the relative value of individual resources needed for the diagnosis and treatment of medical conditions. Future work will add resources for prevention and long term care of these conditions. Once data collection is complete, MONSTR will provide the operational and research communities at NASA with information to support informed decisions regarding areas of research investment, future crew training, and medical supplies manifested as part of any exploration medical system

The Pathway to a Safe and Effective Spaceflight Medication Formulary: Expert Review Panel Recommendations

Exploration spaceflight poses several challenges to the provision of a comprehensive medication formulary. This formulary must accommodate the size and space limitations of the spacecraft, while addressing individual medication needs and preferences of the crew, consequences of a degrading inventory over time, the inability to resupply used or expired medications, and the need to forecast the best possible medication candidates to treat conditions that may occur. The Exploration Medical Capability (ExMC) Element's Pharmacy Project Team has developed a research plan (RP) that is focused on evidence-based models and theories as well as new diagnostic tools, treatments, or preventive measures aimed to ensure an available, safe, and effective pharmacy sufficient to manage potential medical threats during exploration spaceflight. Here, we will discuss the ways in which the ExMC Pharmacy Project Team pursued expert evaluation and guidance, and incorporated acquired insight into an achievable research pathway, reflected in the revised RP

Preterm infant outcomes following COVID-19 lockdowns in Melbourne, Australia

Peer reviewedPublisher PD

Filling the BINs of life: Report of an amphibian and reptile survey of the Tanintharyi (Tenasserim) Region of Myanmar, with DNA barcode data

Despite threats of species extinctions, taxonomic crises, and technological advances in genomics and natural history database informatics, we are still distant from cataloguing all of the species of life on earth. Amphibians and reptiles are no exceptions; in fact new species are described nearly every day and many species face possible extinction. The number of described species continues to climb as new areas of the world are explored and as species complexes are examined more thoroughly. The use of DNA barcoding provides a mechanism for rapidly estimating the number of species at a given site and has the potential to record all of the species of life on Earth. Though DNA barcoding has its caveats, it can be useful to estimate the number of species in a more systematic and efficient manner, to be followed in combination with more traditional, morphology-based identifications and species descriptions. Herein, we report the results of a voucher-based herpetological expedition to the Tanintharyi (Tenasserim) Region of Myanmar, enhanced with DNA barcode data. Our main surveys took place in the currently proposed Tanintharyi National Park. We combine our results with photographs and observational data from the Chaung-naukpyan forest reserve. Additionally, we provide the first checklist of amphibians and reptiles of the region, with species based on the literature and museum. Amphibians, anurans in particular, are one of the most poorly known groups of vertebrates in terms of taxonomy and the number of known species, particularly in Southeast Asia. Our rapid-assessment program combined with DNA barcoding and use of Barcode Index Numbers (BINs) of voucher specimens reveals the depth of taxonomic diversity in the southern Tanintharyi herpetofauna even though only a third of the potential amphibians and reptiles were seen. A total of 51 putative species (one caecilian, 25 frogs, 13 lizards, 10 snakes, and two turtles) were detected, several of which represent potentially undescribed species. Several of these species were detected by DNA barcode data alone. Furthermore, five species were recorded for the first time in Myanmar, two amphibians (Ichthyophis cf. kohtaoensis and Chalcorana eschatia) and three snakes (Ahaetulla mycterizans, Boiga dendrophila, and Boiga drapiezii)

The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation.

Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone\u27s capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis

Subduction Initiation and Early Evolution of the Easton Metamorphic Suite, Northwest Cascades, Washington

The Easton metamorphic suite, in the northwest Cascades of Washington State, preserves an inverted metamorphic sequence with ultramafic rocks underlain by amphibolite and high-temperature blueschist juxtaposed above low-temperature blueschists. The sequence is interpreted as a metamorphic sole and younger accreted rocks that formed during and after the initiation of Farallon plate subduction beneath North America in Jurassic time. Two high-temperature deformation events are recorded in the metamorphic sole at ∼10 kbar and ∼760 °C to 590 °C between \u3e167 and 164 Ma. High-temperature blueschist partly overprints the amphibolite but may have accreted separately at ∼530 °C between ca. 165 and 163 Ma. Retrograde metamorphism and post-tectonic white mica record cooling of the metamorphic sole to ∼350 °C by ca. 160 Ma. Subsequent underplating of the Darrington Phyllite occurred at ∼7 kbar and ∼320 °C prior to ca. 148 Ma until at least ca. 142 Ma. Blueschist-facies conditions and exhumation to ∼5 kbar occurred between ca. 140 and 136 Ma during later accretion and deformation of Shuksan greenschist-blueschist. Cooling ages from the high-temperature metamorphic sole require that subduction began prior to 167 Ma, before or during the formation of ophiolite-related rocks within the Northwest Cascades thrust system. Rapid cooling of the metamorphic sole below 400 °C until ca. 157 Ma through combined thermal relaxation of the subduction zone and partial exhumation was followed by at least 26 m.y. of a steady thermal state as younger units were accreted and exhumed. The record of high-pressure–low-temperature metamorphism suggests that the Easton metamorphic suite formed in a large ocean basin rather than an arc-proximal marginal basin. The metamorphic history also argues against previously suggested correlations of the Easton metamorphic suite with units of the Franciscan complex to the south in California. The temperature-time history of the Easton suite is consistent with models for the early evolution of subduction zones

The PULSE@Parkes project: A new observing technique for long-term pulsar monitoring

The PULSE@Parkes project has been designed to monitor the rotation of radio pulsars over time spans of days to years. The observations are obtained using the Parkes 64-m and 12-m radio telescopes by Australian and international high school students. These students learn the basis of radio astronomy and undertake small projects with their observations. The data are fully calibrated and obtained with the state-of-the-art pulsar hardware available at Parkes. The final data sets are archived and are currently being used to carry out studies of 1) pulsar glitches, 2) timing noise, 3) pulse profile stability over long time scales and 4) the extreme nulling phenomenon. The data are also included in other projects such as gamma-ray observatory support and for the Parkes Pulsar Timing Array project. In this paper we describe the current status of the project and present the first scientific results from the Parkes 12-m radio telescope. We emphasise that this project offers a straightforward means to enthuse high school students and the general public about radio astronomy while obtaining scientifically valuable data sets.Comment: accepted for publication by PAS