Nanoparticle bound nucleic acid probes for DNA detection and gene inactivation

In this project, a gold nanoparticle system has been developed that is able to detect SNP variations through a DNA based anthracene probe. A second probe is bound to the gold nanoparticle which allows the fluorescent output of the anthracene probe to be normalized. This allows the detection of SNP variations without the need for an initial reading, opening the possibility for using this system for cellular SNP identification. Through this work a new method for coating gold nanoparticles in oligonucleotides has been developed. In further work, the use of gold nanoparticles to deliver siRNA into cells and induce gene inactivation was investigated. Efforts to improve the knockdown efficiency of these siRNA-gold nanoparticles were made by integrating a second probe onto the nanoparticle surface, non-specific effects were observed upon addition of this second probe

A Review of Current and Future Weather Data for Building Simulation

This article provides the first comprehensive assessment of methods for the creation of weather variables for use in building simulation. We undertake a critical analysis of the fundamental issues and limitations of each methodology and discusses new challenges, such as how to deal with uncertainty, the urban heat island, climate change and extreme events. Proposals for the next generation of weather files for building simulation are made based on this analysis. A seven-point list of requirements for weather files is introduced and the state-of-the-art compared to this via a mapping exercise. It is found that there are various issues with all current and suggested approaches, but the two areas most requiring attention are the production of weather files for the urban landscape and files specifically designed to test buildings against the criteria of morbidity, mortality and building services system failure

The coalition for conservation genetics: working across organizations to build capacity and achieve change in policy and practice

The Coalition for Conservation Genetics (CCG) brings together four eminentorganizations with the shared goal of improving the integration of geneticinformation into conservation policy and practice. We provide a historicalcontext of conservation genetics as a field and reflect on current barriers toconserving genetic diversity, highlighting the need for collaboration acrosstraditional divides, international partnerships, and coordinated advocacy. Wethen introduce the CCG and illustrate through examples how a coalitionapproach can leverage complementary expertise and improve the organiza-tional impact at multiple levels. The CCG has proven particularly successfulat implementing large synthesis-type projects, training early-career scientists,and advising policy makers. Achievements to date highlight the potential forthe CCG to make effective contributions to practical conservation policy andmanagement that no one“parent”organization could achieve on its own.Finally, we reflect on the lessons learned through forming the CCG, and ourvision for the futur

Role of Cardiorespiratory Fitness and Mitochondrial Oxidative Capacity in Reduced Walk Speed of Older Adults With Diabetes.

Cardiorespiratory fitness and mitochondrial oxidative capacity are associated with reduced walking speed in older adults, but their impact on walking speed in older adults with diabetes has not been clearly defined. We examined differences in cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity between older adults with and without diabetes, as well as determined their relative contribution to slower walking speed in older adults with diabetes. Participants with diabetes (n = 159) had lower cardiorespiratory fitness and mitochondrial respiration in permeabilized fiber bundles compared with those without diabetes (n = 717), following adjustments for covariates including BMI, chronic comorbid health conditions, and physical activity. Four-meter and 400-m walking speeds were slower in those with diabetes. Mitochondrial oxidative capacity alone or combined with cardiorespiratory fitness mediated ∼20-70% of the difference in walking speed between older adults with and without diabetes. Additional adjustments for BMI and comorbidities further explained the group differences in walking speed. Cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity contribute to slower walking speeds in older adults with diabetes

Bringing together approaches to reporting on within species genetic diversity

1. Genetic diversity is one of the three main levels of biodiversity recognised in the Convention on Biological Diversity (CBD). Fundamental for species adaptation to environmental change, genetic diversity is nonetheless under-reported within global and national indicators. When it is reported, the focus is often narrow and confined to domesticated or other commercial species. 2. Several approaches have recently been developed to address this shortfall in reporting on genetic diversity of wild species. While multiplicity of approaches is helpful in any development process, it can also lead to confusion among policy makers and heighten a perception that conservation genetics is too abstract to be of use to organisations and governments. 3. As the developers of five of the different approaches, we have come together to explain how various approaches relate to each other and propose a scorecard, as a unifying reporting mechanism for genetic diversity. 4. Policy implications. We believe the proposed combined approach captures the strengths of its components and is practical for all nations and subnational governments. It is scalable and can be used to evaluate species conservation projects as well as genetic conservation projects.ISSN:0021-8901ISSN:1365-266

An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy

While immunotherapy employing chimeric antigen receptor (CAR) T cells can be effective against a variety of tumor types, little is known about what happens within the tumor at an ultrastructural level during tumor regression. Here, we used transmission electron microscopy to investigate morphologic and cellular features of tumors responding to immunotherapy composed of adoptive transfer of dual-specific CAR T cells and a vaccine, supported by preconditioning irradiation and interleukin-2. Tumors responded rapidly, and large areas of cell death were apparent by 4 days after treatment. The pleomorphic and metabolically active nature of tumor cells and phagocytic activity of macrophages were apparent in electron microscopic images of tumors prior to treatment. Following treatment, morphologic features of various types of tumor cell death were observed, including apoptosis, paraptosis and necrosis. Large numbers of lipid droplets were evident in tumor cells undergoing apoptosis. Macrophages were the predominant leukocyte type infiltrating tumors before treatment. Macrophages decreased in frequency and number after treatment, whereas an increasing accumulation of neutrophils and T lymphocytes was observed following treatment. Phagocytic activity of macrophages and neutrophils was apparent, while T cells could be observed in close association with tumor cells with potential immunological synapses present. These observations highlight the cellular composition and ultrastructural appearance of tumors undergoing regression mediated by immunotherapy

Genetic diversity Goals and Targets have improved, but remain insufficient for clear implementation of the post-2020 global biodiversity framework

Genetic diversity among and within populations of all species is necessary for people and nature to survive and thrive in a changing world. Over the past three years, commitments for conserving genetic diversity have become more ambitious and specific under the Convention on Biological Diversity’s (CBD) draft post-2020 global biodiversity framework (GBF). This Perspective article comments on how goals and targets of the GBF have evolved, the improvements that are still needed, lessons learned from this process, and connections between goals and targets and the actions and reporting that will be needed to maintain, protect, manage and monitor genetic diversity. It is possible and necessary that the GBF strives to maintain genetic diversity within and among populations of all species, to restore genetic connectivity, and to develop national genetic conservation strategies, and to report on these using proposed, feasible indicators

Disruption of cultural burning promotes shrub encroachment and unprecedented wildfires

Recent catastrophic fires in Australia and North America have raised broad-scale questions about how the cessation of Indigenous burning practices has impacted fuel accumulation and structure. For sustainable coexistence with fire, a better understanding of the ancient nexus between humans and flammable landscapes is needed. We used novel palaeoecological modeling and charcoal compilations to reassess evidence for changes in land cover and fire activity, focusing on southeast Australia before and after British colonization. Here, we provide what we believe is the first quantitative evidence that the region’s forests and woodlands contained fewer shrubs and more grass before colonization. Changes in vegetation, fuel structures, and connectivity followed different trajectories in different vegetation types. The pattern is best explained by the disruption of Indigenous vegetation management caused by European settlement. Combined with climate-change impacts on fire weather and drought, the widespread absence of Indigenous fire management practices likely preconditioned fire-prone regions for wildfires of unprecedented extent

Global commitments to conserving and monitoring genetic diversity are now necessary and feasible

Global conservation policy and action have largely neglected protecting and monitoring genetic diversity—one of the three main pillars of biodiversity. Genetic diversity (diversity within species) underlies species’ adaptation and survival, ecosystem resilience, and societal innovation. The low priority given to genetic diversity has largely been due to knowledge gaps in key areas, including the importance of genetic diversity and the trends in genetic diversity change; the perceived high expense and low availability and the scattered nature of genetic data; and complicated concepts and information that are inaccessible to policymakers. However, numerous recent advances in knowledge, technology, databases, practice, and capacity have now set the stage for better integration of genetic diversity in policy instruments and conservation efforts. We review these developments and explore how they can support improved consideration of genetic diversity in global conservation policy commitments and enable countries to monitor, report on, and take action to maintain or restore genetic diversity