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For many years, definition and production of non-renewable resources has been crucial to meeting industrial and societal demands for energy and materials. In the evolving energy transition, the priority is to meet not only the world’s increasing energy requirements but also societal expectations of net zero by 2050 or sooner. Renewable energy will play a key role in achieving this, but this will require key and critical minerals and materials, whether for use in wind turbines or for building new energy distribution systems. Fossil fuels will continue to be used for some energy and industrial processes and increasingly for the production of hydrogen. Essential to the energy transition will be ongoing assessment of resources and reserves, including of critical minerals, geological sites for CO2 and H2, carbon-based and carbon-free fuels. Some of the principles underpinning the traditional use of the terms reserves and resources can be usefully applied to provide rigour and uniformity to the assessment of renewable energy opportunities. Carbon offsets, negative emissions and recycling will also be used to achieve net zero. Whatever the energy transition pathway that countries choose to take, knowledge of and ready access to non-renewable resources and reserves will be essential to achieving a clean energy future.

Adoptive transfer of regulatory T cells (T regs ) is therapeutic in type 1 diabetes (T1D) mouse models. T regs that are specific for pancreatic islets are more potent than polyclonal T regs in preventing disease. However, the frequency of antigen-specific natural T regs is extremely low, and ex vivo expansion may destabilize T regs , leading to an effector phenotype. Here, we generated durable, antigen-specific engineered T regs (EngT regs ) from primary human CD4 + T cells by combining FOXP3 homology-directed repair editing and lentiviral T cell receptor (TCR) delivery. Using TCRs derived from clonally expanded CD4 + T cells isolated from patients with T1D, we generated islet-specific EngT regs that suppressed effector T cell (T eff ) proliferation and cytokine production. EngT regs suppressed T effs recognizing the same islet antigen in addition to bystander T effs recognizing other islet antigens through production of soluble mediators and both direct and indirect mechanisms. Adoptively transferred murine islet-specific EngT regs homed to the pancreas and blocked diabetes triggered by islet-specific T effs or diabetogenic polyclonal T effs in recipient mice. These data demonstrate the potential of antigen-specific EngT regs as a targeted therapy for preventing T1D.

This article details how and why we have developed a flexible and responsive process-based rubric exemplar for teaching, learning, and assessing critical and creative thinking. We hope to contribute to global discussions of and efforts toward instrumentalising the challenge of assessing, but not standardising, creativity in compulsory education. Here, we respond to the key ideas of the four interrelated elements in the critical and creative thinking general capability in the Australian Curriculum learning continuum: inquiring; generating ideas, possibilities, actions; reflecting on thinking processes; and analysing, synthesising and evaluating reasoning and procedures. The rubrics, radical because they privilege process over outcome, have been designed to be used alongside the current NAPLAN tests in Years 5, 7 and 9 to build an Australian-based national creativity measure. We do so to argue the need for local and global measures of creativity in education as the first round of testing and results of the PISA Assessment of Creative Thinking approach and to contribute to the recognition of creative thinking (and doing) as a core twenty-first century literacy alongside literacy and numeracy.

CO2 capture, utilization and storage (CCUS) is recognized as a uniquely important option in global efforts to control anthropogenic greenhouse-gas (GHG) emissions. Despite significant progress globally in advancing the maturity of the various component technologies and their assembly into full-chain demonstrations, a gap remains on the path to widespread deployment in many countries. In this paper, we focus on the importance of business models adapted to the unique technical features and sociopolitical drivers in different regions as a necessary component of commercial scale-up and how lessons might be shared across borders. We identify three archetypes for CCUS development—resource recovery, green growth and low-carbon grids—each with different near-term issues that, if addressed, will enhance the prospect of successful commercial deployment. These archetypes provide a framing mechanism that can help to translate experience in one region or context to other locations by clarifying the most important technical issues and policy requirements. Going forward, the archetype framework also provides guidance on how different regions can converge on the most effective use of CCUS as part of global deep-decarbonization efforts over the long term.

This chapter has grown through dialogue about creative pedagogies across the primary curriculum. The concept of the creative pedagogue traverses subjects, spaces and classes to express the creative synthesis of curriculum into embodied learning experiences for primary aged students. In developing embodied expertise in creative education, Portelli has been inspired by specific educational technologies such as the Learning Pit, Talk Moves, physical strategies for additives and yarning circles with indigenous communities. We focus on two case studies from Portelli’s classroom, firstly a creative and embodied approach to mathematics education and, secondly, reconciliation yarning circles and indigenous gardening. Exploring these examples, we develop a robust model of creative pedagogical practice derived from Portelli’s experience. The model features an educator that embraces creativity as a pivotal component of their pedagogy, enabled systemically by a school environment that allows for diversity of approaches. In examining an educator at the centre of the ecology, we investigate innovation as a starting point and the associated character traits that are driven by choices to be creative as an educator. We offer a practical philosophy, or ethos of practice, along with some pedagogical methods, for primary teachers wanting to practice more creatively.

Summary The identification of microRNA (miRNA) targets by Ago2 crosslinking-immunoprecipitation (CLIP) methods has provided major insights into the biology of this important class of non-coding RNAs. However, these methods are technically challenging and not easily applicable to an in vivo setting. To overcome these limitations and facilitate the investigation of miRNA functions in vivo, we have developed a method based on a genetically engineered mouse harboring a conditional Halo-Ago2 allele expressed from the endogenous Ago2 locus. By using a resin conjugated to the HaloTag ligand, Ago2-miRNA-mRNA complexes can be purified from cells and tissues expressing the endogenous Halo-Ago2 allele. We demonstrate the reproducibility and sensitivity of this method in mouse embryonic stem cells, developing embryos, adult tissues, and autochthonous mouse models of human brain and lung cancers. This method and the datasets we have generated will facilitate the characterization of miRNA-mRNA networks in vivo under physiological and pathological conditions.

Australia has committed to meeting its international obligations to decrease its greenhouse gas emissions including transitioning toward decarbonising its emission-intense energy sector. However, it is facing the dual problems of increasing electricity cost and decreasing energy security. One of the potential contributions to reducing its emission while supplying reliable power is deployment of bioenergy with carbon capture and storage (BECCS). BECCS is a carbon removal technology that offers permanent net removal of carbon dioxide from the atmosphere together with the prospect of negative emissions. The present study was undertaken to assess the potential contribution of BECCS to achieving long term decarbonising of the Australian energy sector. This study considers the availability of sustainable bioenergy resources and the economic viability and environmental impacts of BECCS. In order to avoid the ecological uncertainties and social challenges of dedicated energy crops, this study focuses on organic waste from the municipal, agricultural, and forestry sectors. Based on the quantity of biomass resources available, BECCS options in Australia have the potential to remove a total of 25 million tonne CO2/year from the atmosphere as negative emissions by 2050. In addition, BECCS systems could supply Australia with up to 13.7 terawatt-hours of renewable power by mid-century which is around 3.6% of expected gross electricity generation in 2050. Deployment of BECCS as a reliable supplier of electricity would potentially enhance the flexibility and diversity of Australia’s energy portfolio and remove carbon dioxide from the atmosphere. However, deployment of BECCS as a carbon negative strategy will require strong policy support.

Bioenergy with Carbon Capture and Storage (BECCS) is a carbon removal technology that offers permanent net removal of carbon dioxide (CO2) from the atmosphere. One of the significant bioenergy resources is organic waste collected from municipal solid waste (MSW). The goal of this study was to provide an estimate of the global potential for using municipal solid waste as a resource for bioenergy with carbon capture and storage (BECCS) and to compare the feasibility of two specific BECCS options: municipal solid waste incineration with carbon capture and storage (MSW-CCS), and landfill gas combusted in a gas turbine with carbon capture and storage (LFG-CCS). To assess the feasibility of MSW-based BECCS options, techno-economic and environmental impact assessments were conducted. In the case of a “business-as-usual” scenario with no emission policy in effect, the levelised cost of electricity production from both BECCS options is higher than a coal power plant with CCS. However, these BECCS systems offer a lower cost of avoided CO2. Introducing renewable energy certificates or negative emission refund schemes to BECCS has a significant impact on the economic viability of these technologies in coal-dominant power markets. Environmental impact assessment shows that around 0.7 kg CO2-eq is removed for each kg of wet MSW incinerated, for the MSW-CCS scenario. This translates to approximately negative 2.8 billion tonnes CO2 if all the available 4 billion tonnes MSW generated per year by 2100 is utilised in a MSW-CCS system. The net GHG emission of the LFG-CCS system with an average LFG collection rate of 75% was 0.56 kg CO2-eq. Challenges include the dispersed nature of MSW resources and the lack of economic support schemes, such as commonly apply to solar and wind. Nonetheless, MSW-based BECCS technologies have significant potential for abating and in some cases removing considerable amounts of the greenhouse gases from the atmosphere, thereby contributing significantly to the COP21 emission reduction targets.

Bioenergy with carbon capture and storage (BECCS) involves the conversion of biomass to energy, producing CO2 which is sequestered, transported and then permanently stored in a suitable geological formation. Thus, a negative flow of CO2 from the atmosphere to the subsurface is established. The potential of BECCS to remove CO2 from the atmosphere (in addition to generating energy) makes it an attractive approach to help achieving the ambitious global warming targets of COP 21. BECCS has a range of variables such as the type of biomass resource, the conversion technology, the CO2capture process used and storage options. Each of the pathways to connect these options has its own environmental, economic and social impacts. This study attempts to integrate these impacts into a three pillar sustainability framework (3PSF) approach. As an example, the 3PSF approach is applied to bioenergy from organic waste collected from municipal solid waste (MSW). Global and Australian potentials for using municipal solid waste as resource for bioenergy and coupling it with carbon capture and storage (BECCS), was investigated. Two BECCS systems, municipal solid waste incineration with carbon capture and storage (MSW-CCS) and landfill gas combusted in gas turbine with carbon capture and storage (LFG-CCS) were modelled. In the case of business-as-usual scenarios with no emission policy in place, the cost of electricity from both BECCS options is higher than for unmitigated coal power generation. However, introducing renewable energy certificate or negative emission refunding schemes has a significant impact on the economic viability of these technologies. Environmental impact assessments show that in the MSW-CCS model, for each kg of wet MSW incinerated around 0.7 kg CO2,eq is removed from the atmosphere. BECCS has the potential to be a valuable step towards a low-carbon energy system. However, if planned unsustainably it could compromise the natural ecosystem and social equity. The importance of the presented study is in its holistic approach to assessing the sustainability of different BECCS routes and providing a comprehensive adaptive management system that enables decision-makers to plan BECCS options in a transparent and timely manner.

SUMMARYThe identification of miRNA targets by Ago2 crosslinking-immunoprecipitation (CLIP) methods has provided major insights into the biology of this important class of non-coding RNAs. However, these methods are technically challenging and not easily translated to an in vivo setting. To overcome these limitations and to facilitate the investigation of miRNA functions in mice, we have developed a method (HEAP: for Halo-Enhanced Ago2 Pulldown) to map miRNA-mRNA binding sites. This method is based on a novel genetically engineered mouse harboring a conditional, Cre-regulated, Halo-Ago2 allele expressed from the endogenous Ago2 locus. By using a resin conjugated to the HaloTag ligand, Ago2-miRNA-mRNA complexes can be efficiently purified from cells and tissues expressing the endogenous Halo-Ago2 allele. We demonstrate the reproducibility and sensitivity of this method in mouse embryonic stem cells, in developing embryos, in adult tissues and in autochthonous mouse models of human brain and lung cancers.The tools and the datasets we have generated will serve as a valuable resource to the scientific community and will facilitate the characterization of miRNA functions under physiological and pathological conditions.

Surveillance for invading insect pests is costly and the trapper usually finds the traps empty of the target pest. Since the successful establishment of new pests is an uncommon event, multiple lures placed into one trap might increase the efficiency of the surveillance system. We investigated the effect of the combination of the Tephritidae male lures – trimedlure, cuelure, raspberry ketone and methyl eugenol – on catch of Ceratitis capitata, Zeugodacus cucurbitae, Bactrocera tryoni, B. dorsalis, B. aquilonis and B. tenuifascia in Australia and the USA (not all species are present in each country). The increase in trap density required to offset any reduction in catch due to the presence of lures for other Tephritidae was estimated. The effect of increasing trap density to maintain surveillance sensitivity was modelled for a hypothetical population of B. tryoni males, where the effective sampling area of cuelure traps for this species has been estimated. The 3-way combination significantly reduced the catch of the methyl eugenol-responsive B. dorsalis. Unexpectedly, we found that trimedlure-baited traps that contained methyl eugenol had ×3.1 lower catch of C. capitata than in trimedlure-only-baited traps in Australia, but not in Hawaii where no difference in catch was observed, we cannot satisfactorily explain this result. Based on the data presented here and from previous research, combinations of some male lures for the early detection of tephritid flies appear compatible and where there is any reduction in surveillance sensitivity observed, this can be offset by increasing the density of traps in the area.

The explosion in genome editing technologies that has occurred in the past decade has revolutionized cancer research and promises to improve cancer diagnosis and therapy. Ongoing efforts include engineering of chimeric antigen receptor-T cells using clustered regularly interspaced short palindromic repeats (CRISPR) to generate a safer, more effective therapy with improved performance in immunologically "cold" tumors, as well as clever adaptations of CRISPR enzymes to allow fast, simple, and sensitive detection of specific nucleotide sequences. While still in their infancy, CRISPR-based cancer therapeutics and diagnostics are developing at an impressive speed and it is likely they will soon impact clinical practice. Here, we summarize their history and the most recent developments.

Environmental artists are ecologically and politically motivated to change the way we view our world. Artists undertake the production of art and activism, where the art-making becomes more than art; it becomes activism; a way that allows for raising awareness; a way to retrieve, express and communicate a political message. Here, diverse creativities (including intercultural, interdisciplinary, and artistic creativity) enable forms of authorship with particular kinds of power and capacity. In this chapter, We draw on three activist enquiry practices which embody: (i) intercultural creativity through an activist choreographic practice involving a Greenlandic and Scandinavian dance company; (ii) transdisciplinary creativity through an arts-based environmental education practice inspired by an activist sculpture involving a primary school in the UK; and (ii) artistic creativity inspired by an artist activist residency practice in a Higher Education setting in the UK. Each practice features artist-researcher collaborations. Each practice involves arts as activism. Each practice makes explicit an understanding of the body as inscriptor, where the relationship between the body, power and the authoring of diverse creativities is crucial in the embodiment of arts practice as research and arts education. Each practice as research stimulates reflection and discussion by teachers, students, artists, researchers and policy makers interested in what it might mean to live the arts-as-political-as-embodiment in creating practice as research where arts activism, diverse creativities and embodiment is manifest.

The widespread application of high-throughput sequencing methods is resulting in the identification of a rapidly growing number of novel gene fusions caused by tumour-specific chromosomal rearrangements, whose oncogenic potential remains unknown. Here we describe a strategy that builds upon recent advances in genome editing and combines ex vivo and in vivo chromosomal engineering to rapidly and effectively interrogate the oncogenic potential of genomic rearrangements identified in human brain cancers. We show that one such rearrangement, an microdeletion resulting in a fusion between Brevican (BCAN) and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), is a potent oncogenic driver of high-grade gliomas and confers sensitivity to the experimental TRK inhibitor entrectinib. This work demonstrates that BCAN-NTRK1 is a bona fide human glioma driver and describes a general strategy to define the oncogenic potential of novel glioma-associated genomic rearrangements and to generate accurate preclinical models of this lethal human cancer.

Earth scientists have made a major contribution over the last century to extracting materials from the ground. Many of those same skills will be used to be applied to put materials into the ground in a more intelligent and more sustainable manner, whether that material is water, nuclear or toxic waste or perhaps even CO2. We also need to refocus some of the available earth science expertise so that we can develop a better understanding of soil formation and erosion, surficial processes and landscape evolution. Universities, research institutions and geological surveys must become more concerned about the surface and near surface issues and perhaps less concerned with the core and lower mantle. Finally, the earth scientist must be active in Our life support system is the consequence of, and dependent on a complex interplay of physical chemical and biological processes. Those processes are being increasingly perturbed by human activity. A common perception is that the earth scientist is mainly concerned with “the problem” through involvement in resource extraction but in fact the earth sciences have a key role to play in “the solution”. Contributing to solving problems of sustainability requires earth science involvement in determining the nature magnitude and rate of change, both pre-anthropogenic and anthropogenic. But more than this, earth scientists can contribute directly to the resolution of many identified problems whether in the urban environment, the coastal zone, the subsurface or the atmosphere. But this will require the application of existing skills in new ways. For example seeking a strengthened dialogue with other disciplines including planners, environmentalists, sociologists, economists, and many others if we are to sustain our life support system for the benefit of present and future generations.

Improving our understanding of trapping, including how we might be able to enhance it temporally and spatially, would add to our level of confidence in the long term secure geological storage of CO2 in both open and closed saline aquifer systems. This knowledge could also provide the basis for designing quantitative rules for site abandonment based on measured trapping and residual gas saturations. Fluid transport, geochemical processes and associated CO2 trapping mechanisms in geological reservoirs are highly dependent on the nature of structural and lithological heterogeneities. But important centimetre to meter scale heterogeneities are incorrectly incorporated or not incorporated at all into storage complex models, because they can neither be seismically imaged nor represented by grid cells. The GeoCquest Project is focused on determining residual, dissolution and mineral trapping over time for open and closed saline aquifers, through a series of coordinated studies at a range of scales, using experimental, analytical and numeric approaches. This paper describes some of the GeoCquest work currently underway.

This chapter works through a series of methodological experimentations with movement and materiality in order to explore the potentials of environmental arts pedagogies. We address the question of what environmental arts pedagogies might come to look like in the ever-changing contexts of children’s social and environmental worlds. This leads us to engage with the movements and materialities of learning environments as they come to co-compose pedagogical encounters. In doing so, we draw on new materialist accounts of matter as agentic, fluid and dynamic; movement as a choreographic architecting of experience; and a/r/tographic approaches to pedagogical engagement and embodied practice. Taking up the use of concepts as methods, we develop a series of artistic and pedagogical experimentations with concepts of ‘corridors’, ‘flight’, ‘viscosity’ and ‘construction’. In teasing out the implications of these concepts for an environmental arts pedagogy, we combine imagery and text to both render and diagram the movement of bodies, materials and environments in passage through each of these four conceptual enactments. This leads us to develop a series of propositions for an environmental arts pedagogy based on our creative research process. In doing so, we aim to sketch the contours of an environmental arts pedagogy that combines the speculative imagination with embodied, sensorial, and empirical experiences.

In Arts education, and specifically for Dance, the challenge for tertiary educators is to provide authentic, artful experiences with the aim of developing teachers capable of delivering authentic Dance curriculum. The limited time allocated to the Arts necessitates strategic focus on the design of the unit and the development of engaging artistic assessment tasks. Codifying learning activities around choreographic practice provides students with access irrespective of prior learning and offers robust Arts-based experiences. The questions emerging from the research are as follows: 1. How does the unit organisation enhance students’ artistic learning? 2. How does offering authentic choreographic experiences and assessment enhance students’ appreciation of Dance as an Art form? 3. How could these choreographic experiences better prepare students for their future role as generalist teachers? This chapter describes a pilot study that explored students’ understanding of Dance and how their artistic assessable tasks enabled them as artists, researchers and teachers.

The widespread application of high-throughput sequencing methods is resulting in the identification of a rapidly growing number of novel gene fusions caused by tumour-specific chromosomal rearrangements, whose oncogenic potential remains unknown. Here we describe a strategy that builds upon recent advances in genome editing and combines ex vivo and in vivo chromosomal engineering to rapidly and effectively interrogate the oncogenic potential of genomic rearrangements identified in human brain cancers. We show that one such rearrangement, an microdeletion resulting in a fusion between Brevican (BCAN) and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), is a potent oncogenic driver of high-grade gliomas and confers sensitivity to the experimental TRK inhibitor entrectinib. This work demonstrates that BCAN-NTRK1 is a bona fide human glioma driver and describes a general strategy to define the oncogenic potential of novel glioma-associated genomic rearrangements and to generate accurate preclinical models of this lethal human cancer., The use of mouse models has been an invaluable resource in cancer research but their generation is lengthy and costly. Here the authors describe an approach to generate engineered mouse models carrying specific gene fusions and, as a proof of principle, show that Bcan-Ntrk1 fusion leads to glioblastomas.

SummaryHair follicle stem cells (HFSCs) and their transit amplifying cell (TAC) progeny sense BMPs at defined stages of the hair cycle to control their proliferation and differentiation. Here, we exploit the distinct spatial and temporal localizations of these cells to selectively ablate BMP signaling in each compartment and examine its functional role. We find that BMP signaling is required for HFSC quiescence and to promote TAC differentiation along different lineages as the hair cycle progresses. We also combine in vivo genome-wide chromatin immunoprecipitation and deep-sequencing, transcriptional profiling, and loss-of-function genetics to define BMP-regulated genes. We show that some pSMAD1/5 targets, like Gata3, function specifically in TAC lineage-progression. Others, like Id1 and Id3, function in both HFSCs and TACs, but in distinct ways. Our study therefore illustrates the complex differential roles that a key signaling pathway can play in regulation of closely related stem/progenitor cells within the context of their overall niche.

A review has been undertaken of small scale injection projects of less than 100,000 tonnes (t) of CO2 from around the world, with the objective of assisting countries or organisations wishing to embark on their first CO2 injection test, in a cost effective, time efficient and safe manner. The mean amount of CO2 injected per project was approximately 1,000 t; only 9 out of the 45 projects had injected more than 10,000 t. Costs varied greatly from less than $1 million to $100 million, with the mean total cost in the range of $10-20 million. Half of the projects were based on injection into sandstone reservoirs, although a significant number (28%) involved injection into coals. The source of the CO2 was quite variable; the majority of the CO2 was transported by truck to the site. The depth of injection ranged from approximately 300m to over 4,000m but averaged around 1,200m. The time taken from making the preliminary decision to undertake a project to injection of the first molecule of CO2 was variable but averaged approximately three years. Generally, small scale projects are opportunistic, typically initiated by research organisations; they rely on an alliance with industrial partners for operational expertise and access to suitable locations. In most small scale projects, pre-drill reservoir characterisation consists of the integration of pre-existing geological and hydrological data. Saline reservoir sites are usually data deficient. Reservoir simulations are performed routinely, using a variety of codes, to assess CO2 injection tests and provide valuable information for system design, permitting, and monitoring. The simulations are also useful for providing a systematic framework for integrating site characterisation data, visualisation of model results provide a valuable communication tool. Documentation of storage risk assessment by projects was limited. Monitoring programs for the test injection projects were opportunistic to some degree, utilising existing data to help in establishing a baseline and commonly utilising existing wells for down-hole observations and monitoring-based sampling. Nearly all projects undertook pressure and temperature monitoring as a standard. These small scale projects offer a cost effective way of demonstrating storage technologies in CCS, assisting the progression towards large scale injections.

Despite previous studies investigating selenium (Se) redox reactions in the presence of semiconducting minerals, Se redox reactions mediated by galena (PbS) are poorly understood. In this study, the redox chemistry of Se on galena is investigated over a range of environmentally relevant Eh and pH conditions (+0.3 to &minus, 0.6 V vs. standard hydrogen electrode, SHE, pH 4.6) using a combination of electrochemical, spectroscopic, and computational approaches. Cyclic voltammetry (CV) measurements reveal one anodic/cathodic peak pair at a midpoint potential of +30 mV (vs. SHE) that represents reduction and oxidation between HSeO3&minus, and H2Se/HSe&minus, Two peak pairs with midpoint potentials of &minus, 400 and &minus, 520 mV represent the redox transformation from Se(0) to HSe&minus, and H2Se species, respectively. The changes in Gibbs free energies of adsorption of Se species on galena surfaces as a function of Se oxidation state were modeled using quantum-mechanical calculations and the resulting electrochemical peak shifts are (&minus, 0.17 eV for HSeO3&minus, /H2Se, &minus, 0.07 eV for HSeO3&minus, /HSe&minus, 0.15 eV for Se(0)/HSe&minus, and &minus, 0.15 eV for Se(0)/H2Se). These shifts explain deviation between Nernstian equilibrium redox potentials and observed midpoint potentials. X-ray photoelectron spectroscopy (XPS) analysis reveals the formation of Se(0) potentials below &minus, 100 mV and Se(0) and Se(&minus, II) species at potentials below &minus, 400 mV.

Low-grade gliomas account for ~30% of primary central nervous system tumors arising in children. Although LGGs grow slowly, inoperable tumors can lead to morbidity and premature death. The most common oncogenic event observed in nearly 70% of cases of Pilocytic astrocytomas (PA) and diffuse leptomeningeal glioneuronal tumors (DLGT)—is a recurrent tandem duplication on chromosome 7. This complex rearrangement results in the fusion of BRAF C-Terminus comprising of the kinase domain with KIAA1549 N-Terminus, an uncharacterized gene. Apart from creating this fusion, the entire region between KIAA1549 and BRAF comprising of 17 protein coding genes is duplicated. Currently, there are no accurate preclinical models for KIAA1549-BRAF duplication which has hindered targeted therapy for this class of pediatric brain tumors. Although cDNA overexpression of KIAA1549-BRAF has been shown to activate the MAPK pathway, in vivo models overexpressing the fusion protein lack the physiological features of either PA or DLGT. Our hypothesis in this project is that generating the entire tandem duplication event in addition to the Kiaa1549-Braf fusion is necessary for modeling the patho-physiological characteristics of the pediatric brain tumors. We have employed CRISPR based somatic genome editing to generate the tandem duplication of Kiaa1549-Braf in p53-/- adult neural stem cells ex-vivo, which results in brain tumors predominantly growing in the subarachnoid/leptomeningeal space and displays histopathological features of human DLGT. Further, we have shown that the Kiaa1549-Braf driven tumor lines can be inhibited by next generation Braf dimer inhibitors. In summary, we have developed a new preclinical model for Kiaa1549-Braf driven brain cancer and demonstrated efficacy against a new preclinical Braf inhibitor.

Thirteen CCS projects involving the capture and/or storage of carbon dioxide in Australia are currently proposed or underway. The projects range in maturity from Australia’s first storage project (the CO2CRC Otway Project) and the CSIRO Loy Yang PCC Pilot Project which are already underway, to projects which are unlikely to be fully operational until 2015 or later. They range in scale from relatively modest pilot scale capture projects (Munmorah, Hazelwood, CO2CRC H3, Mulgrave, Loy Yang), to commercially significant rates of CO 2 storage of 10–50,000 tonnes CO 2 per annum (Callide Oxyfuel, Otway) to proposals for medium scale injection of up to 500,000 tonnes CO 2 per annum (ZeroGen, Coolimba), 3–4 million tonnes per annum for the Gorgon LNG Project and up to 10 million tonnes of CO 2 per annum for the Monash (coal to liquids) Project. It is encouraging to see this high level of interest in CCS in Australia. At the same time it has to be recognised that most of these projects have not advanced beyond the feasibility scale at this time and not all of them will prove to be commercially or environmentally viable. Additionally, several of the existing CCS projects have been at the feasibility stage for several years and the slow rate of progress is a concern given the importance of CCS deployment to Australia. Australia is seen as one of the leaders in the demonstration and deployment of CCS, with billions of dollars committed to CCS by industry and governments over the next 5–10 years. Nonetheless, it is important to examine ways of further accelerating the large-scale deployment of CCS by resolving outstanding issues including financial, liability and other questions which may be impeding progress.

Life and death fate decisions allow cells to avoid massive apoptotic death in response to genotoxic stress. Although the regulatory mechanisms and signalling pathways controlling DNA repair and apoptosis are well characterized, the precise molecular strategies that determine the ultimate choice of DNA repair and survival or apoptotic cell death remain incompletely understood. Here we report that a protein tyrosine phosphatase, EYA, is involved in promoting efficient DNA repair rather than apoptosis in response to genotoxic stress in mammalian embryonic kidney cells by executing a damage-signal-dependent dephosphorylation of an H2AX carboxy-terminal tyrosine phosphate (Y142). This post-translational modification determines the relative recruitment of either DNA repair or pro-apoptotic factors to the tail of serine phosphorylated histone H2AX (gamma-H2AX) and allows it to function as an active determinant of repair/survival versus apoptotic responses to DNA damage, revealing an additional phosphorylation-dependent mechanism that modulates survival/apoptotic decisions during mammalian organogenesis.

Background In glioblastoma (GBM), Id1 serves as a functional marker for self-renewing cancer stem-like cells. We investigated the mechanism by which cyclooxygenase-2 (Cox-2)-derived prostaglandin E2 (PGE2) induces Id1 and increases GBM self-renewal and radiation resistance. Methods Mouse and human GBM cells were stimulated with dimethyl-PGE2 (dmPGE2), a stabilized form of PGE2, to test for Id1 induction. To elucidate the signal transduction pathway governing the increase in Id1, a combination of short interfering RNA knockdown and small molecule inhibitors and activators of PGE2 signaling were used. Western blotting, quantitative real-time (qRT)-PCR, and chromatin immunoprecipitation assays were employed. Sphere formation and radiation resistance were measured in cultured primary cells. Immunohistochemical analyses were carried out to evaluate the Cox-2-Id1 axis in experimental GBM. Results In GBM cells, dmPGE2 stimulates the EP4 receptor leading to activation of ERK1/2 MAPK. This leads, in turn, to upregulation of the early growth response1 (Egr1) transcription factor and enhanced Id1 expression. Activation of this pathway increases self-renewal capacity and resistance to radiation-induced DNA damage, which are dependent on Id1. Conclusions In GBM, Cox-2-derived PGE2 induces Id1 via EP4-dependent activation of MAPK signaling and the Egr1 transcription factor. PGE2-mediated induction of Id1 is required for optimal tumor cell self-renewal and radiation resistance. Collectively, these findings identify Id1 as a key mediator of PGE2-dependent modulation of radiation response and lend insight into the mechanisms underlying radiation resistance in GBM patients.

Reduction of U(VI) to U(IV) on mineral surfaces is often considered a one-step two-electron process. However, stabilized U(V), with no evidence of U(IV), found in recent studies indicates U(VI) can undergo a one-electron reduction to U(V) without further progression to U(IV). We investigated reduction pathways of uranium by reducing U(VI) electrochemically on a magnetite electrode at pH 3.4. Cyclic voltammetry confirms the one-electron reduction of U(VI) to U(V). Formation of nanosize uranium precipitates on the magnetite surface at reducing potentials and dissolution of the solids at oxidizing potentials are observed by in situ electrochemical atomic force microscopy. XPS analysis of the magnetite electrodes polarized in uranium solutions at voltages from -0.1 to -0.9 V (E(0)(U(VI)/U(V))= -0.135 V vs Ag/AgCl) show the presence of only U(V) and U(VI). The sample with the highest U(V)/U(VI) ratio was prepared at -0.7 V, where the longest average U-O(axial) distance of 2.05 ± 0.01 Å was evident in the same sample revealed by extended X-ray absorption fine structure analysis. The results demonstrate that the electrochemical reduction of U(VI) on magnetite only yields U(V), even at a potential of -0.9 V, which favors the one-electron reduction mechanism. U(V) does not disproportionate but stabilizes on magnetite through precipitation of mixed-valence state U(V)/U(VI) solids.

The CO2CRC Otway Project, is Australia's first demonstration of geological storage of CO2. During 2008–2009 approximately 65 000 t of 80/20 CO2 and methane were injected into a depleted gas field at a depth of approximately 2000 m. An extensive programme of monitoring was put in place of the Waarre Sandstone reservoir and the overlying intervals such as aquifers, soils and the atmosphere. It proved difficult to use 3D seismic to monitor CO2 behaviour in the depleted gas field because of the presence of residual methane, but U-tube sampling provided important insights into the speed of migration of CO2 within the reservoir and associated geochemical changes. Extrapolation of Otway results to depleted gas fields suggests they could be a major storage opportunity. A new programme of carbon capture and storage research at the site is being done, with a range of innovative experiments, further advancing knowledge of CO2 storage.

The wish on the part of many governments to decrease the overall level of their expenditure, coupled with the desire to ensure that science is made more relevant to national priorities, is driving many of the changes occurring in science. In Britain ‘market forces’, including contracting out, market testing and privatization, have been used as mechanisms for changing institutional and ownership arrangements. There have been a number of gains from this approach but there have also been significant costs. The search for relevance has resulted in a number of countries undertaking technology foresight exercises. Most of them follow a similar methodology, though the UK exercise is notable for its size and scope. The trend towards ‘outsourcing’ of research by many private industries has received less attention than it deserves in terms of national science policy, for it is a fundamental change in the way that industry obtains its science. Unless ‘outsourcing’ is supported by well-established national and international research and training networks, it could result in problems for some industries in the longer term. Scientific institutions in the public sector will be increasingly dependent on a range of funding sources and a model is presented that provides a framework within which the requirements of the public and private sectors can be accommodated while still maintaining scientific excellence, impartiality and credibility and offering the opportunity to address public-good issues. It is likely in the future that the countries most effectively exploiting their science base will have undertaken successful foresight exercises. They will also have established strong links between research and its application by developing comprehensive and effective national research and training networks that also link into global networks. These will be supported by well-defined institutional arrangements, including intermediate institutes with a specific responsibility for undertaking strategic and applied science underpinned by basic research and for maintaining and strengthening networks.

Cellular aging is linked to deficiencies in efficient repair of DNA double strand breaks and authentic genome maintenance at the chromatin level. Aging poses a significant threat to adult stem cell function by triggering persistent DNA damage and ultimately cellular senescence. Senescence is often considered to be an irreversible process. Moreover, critical genomic regions engaged in persistent DNA damage accumulation are unknown. Here we report that 65% of naturally occurring repairable DNA damage in self-renewing adult stem cells occurs within transposable elements. Upregulation of Alu retrotransposon transcription upon ex vivo aging causes nuclear cytotoxicity associated with the formation of persistent DNA damage foci and loss of efficient DNA repair in pericentric chromatin. This occurs due to a failure to recruit of condensin I and cohesin complexes. Our results demonstrate that the cytotoxicity of induced Alu repeats is functionally relevant for the human adult stem cell aging. Stable suppression of Alu transcription can reverse the senescent phenotype, reinstating the cells' self-renewing properties and increasing their plasticity by altering so-called "master" pluripotency regulators.

John Bradshaw is Project Manager of Project 1 (Regional Analysis) in the GEODISC research project at the Australian Petroleum Cooperative Research Centre. He has a B.Sc. (Honours) and Ph.D. in Applied Geology from the University of New South Wales. John is an exploration technologist, with a regional knowledge of Australian sedimentary basins, and is employed as a Principal Research Scientist at the Australian Geological Survey Organisation. He has also worked for Esso (Australia) and on staff exchange for a year with WMC Petroleum and Ampolex/Mobil. He has extensive fieldwork experience throughout central Australia and Papua New Guinea, where he consulted for several years. John has previously run major industry-funded research projects examining the petroleum systems of Australia. He is a member of GSA, PESA, and AAPG. Peter Cook is currently Executive Director of the Australian Petroleum Cooperative Research Centre (APCRC) and a director of various companies. Previous positions include Senior Research Fellow (Australian National University), Division Chief-Associate Director (Australian Geological Survey), and Director of the British Geological Survey (1990–1998). It was during his time as Director of BGS that he became interested in the issue of geological sequestration of CO2, and on his return to Australia he established the GEODISC program of the APCRC. He has acted as an adviser to government organizations and companies in Europe, Asia, Australia, and North America, and he has held academic positions in Australia, the United States, France, and the United Kingdom. Peter Cook holds degrees in geology from the United Kingdom, Australia, and the United States. His research career has included studies of the sedimentology, geochemistry, and economic geology of ancient and modern environments in both inland and coastal parts of Australia and the evolution of Australia over the past 500 million years. He was leader of a major UNESCO program …

Publisher Summary Nuclear receptors are modular proteins characterized by a central zinc finger coordinated DNA binding domain, a C-terminal ligand binding domain (LBD), and a variable N-terminal domain. The LBD consists of a number of layered anti-parallel α-helices assembled to form a ligand binding cavity with a protruding C-terminal α-helix (AF-2) that changes position upon ligand binding. In the absence of hormone, corepressors including NCoR and SMRT interact with the receptor LBD through an elongated helix containing variations of the sequence LXXI/HIXXXI/L, also referred to as the CoRNR-box. NCoR and SMRT are huge adaptor proteins that interact with the same NR hydrophobic pocket contacted by alternate coregulatory factors characterized by LXXLL motifs. HDAC3 plays a major role in nuclear receptor corepressor activity for many transcriptional targets. HDAC3 activity is mediated by direct association with NCoR/SMRT through interaction with one of the two highly conserved domains originally identified in SWI3, ADA2 and TFIIIB, termed the SANT domain. HDAC3 can be localized to the inner cytoplasmic membrane and the cytoplasm, in addition to the nucleus. The primary amino acid sequence reveals two nuclear export signals on HDAC3 and a C-terminal nuclear localization signal (NLS). Subcellular localization of HDAC3 has been attributed to a number of posttranslational modifications. During apoptosis, caspase dependent cleavage of HDAC3 separates the C-terminal NLS from the catalytic domain and HDAC3 enzymatic activity is relegated to the cytoplasm and can associate with IкB. Enzymatic activity of HDAC3 can also be regulated by posttranslation modification.

There was a very significant and widespread phosphogenic event around the Proterozoic-Phanerozoic transition. This is reflected in the occurrence of many major and minor latest Proterozoic and Cambrian phosphate deposits (phosphorites) in Asia, Australia, Africa and South America, as well as minor occurrences in many other parts of the world. The major peak in phosphogenesis was in the Tommotian, with lesser events in the Ediacaran and the Lenian, bracketed by other minor though significant events. Recent evidence on the timing of Proterozoic phosphogenesis does not now support the suggestion of a phosphogenesis-glaciation link. These peaks in phosphogenesis are taken as evidence that there was a marked increase in the phosphate content of the shallow seas at about this time, possibly as a result of the circulation of deep, phosphorus-rich ocean waters into the photic zone. Not only was this responsible for the formation of phosphorites but it also had a profound effect on the biota, and may have been a driving mechanism for the Cambrian faunal ‘explosion’ and the initiation of biomineralization.