105 research outputs found
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Simulating the Martian Chemical Enivronment
We report on new analogue materials to simulate Martian rocks and soils, especially under realistic redox conditions
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The Physio-Chemical Properties for the Interior of Enceladus
We have reviewed the current physical and chemical conditions of the Enceladus sub-surface environment, including the composition, temperature, pH and pressure. Here we have defined some of these parameters and, through the aid of modelling, will define and refine the remaining parameters needed for our experimental work. Simulations of the chemical reactions occurring within Enceladus can then be carried
out to advance our understanding of the internal environment of Enceladus and help evaluate its potential habitability. Once a better understanding of the chemical reactions occurring at the rock-water interface has been carried out, then potential analogues on Earth can be evaluated and known microbial life can be tested to see if it could survive the conditions of Enceladus
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Temozolomide resistance in glioblastoma cells occurs partly through epidermal growth factor receptor-mediated induction of connexin 43
Glioblastoma Multiforme (GBM) is an aggressive adult primary brain tumor with poor prognosis. GBM patients develop resistance to the frontline chemotherapy, temozolomide (TMZ). As the connexins (Cx) have been shown to have a complex role in GBM, we investigated the role of Cx43 in TMZ resistance. Cx43 was increased in the TMZ-resistant low passage and cell lines. This correlated with the data in The Cancer Genome Atlas. Cx43 knockdown, reporter gene assays, chromatin immunoprecipitation assay, real-time PCR and western blots verified a role for Cx43 in TMZ resistance. This occurred by TMZ-resistant GBM cells being able to activate epidermal growth factor receptor (EGFR). In turn, EGFR activated the JNK-ERK1/2-AP-1 axis to induce Cx43. The increased Cx43 was functional as indicated by gap junctional intercellular communication among the resistant GBM cells. Cell therapy could be a potential method to deliver drugs, such as anti-EGF to tumor cells. Similar strategies could be used to reverse the expression of Cx43 to sensitize GBM cells to TMZ. The studies showed the potential for targeting EGF in immune therapy. These agents can be used in conjunction with stem cell therapy to treat GBM
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Simulating microbial processes in extraterrestrial, aqueous environments
Finding evidence of life elsewhere in the Solar System is dependent on understanding biotic processes that could occur within potentially habitable environments. Here, we describe a suite of high-pressure flow-through chambers that have been developed to investigate biotic and abiotic processes within simulated sub-surface martian and icy moon environments
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Characterising the Transfer of Biomarkers within the Phobos-Mars System
Procedural and analytical developments required for impact and heat investigation into the detection of biomarkers transported from Mars to Phobos
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The identification of sulfide oxidation as a potential metabolism driving primary production on late Noachian Mars
The transition of the martian climate from the wet Noachian era to the dry Hesperian (4.1–3.0 Gya) likely resulted in saline surface waters that were rich in sulfur species. Terrestrial analogue environments that possess a similar chemistry to these proposed waters can be used to develop an understanding of the diversity of microorganisms that could have persisted on Mars under such conditions. Here, we report on the chemistry and microbial community of the highly reducing sediment of Colour Peak springs, a sulfidic and saline spring system located within the Canadian High Arctic. DNA and cDNA 16S rRNA gene profiling demonstrated that the microbial community was dominated by sulfur oxidising bacteria, suggesting that primary production in the sediment was driven by chemolithoautotrophic sulfur oxidation. It is possible that the sulfur oxidising bacteria also supported the persistence of the additional taxa. Gibbs energy values calculated for the brines, based on the chemistry of Gale crater, suggested that the oxidation of reduced sulfur species was an energetically viable metabolism for life on early Mar
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Composition and Habitability of Europa’s Ocean Over Time
Introduction: Europa is proposed to host a global liquid water ocean that is in contact with a silicate interior [1]. Understanding the composition of this ocean and the underlying rock is crucial for evaluating the habitability of Europa. However, the presence of an ice shell impedes direct observation or analysis of the ocean and rock, leaving their compositions largely unknown. Previous modelling work has shown that, if Europa accreted entirely from CI or CM chondritic material, sufficient volatiles could be released during prograde metamorphism to account for the current size of the hydrosphere [2]. However, thermal models predict that temperatures in Europa’s interior would gradually increase over billions of years [e.g. 3], where the progressive release of volatiles would change the ocean composition over time. In this study, possible ocean compositions were explored using computer modelling to simulate the thermal evolution of Europa’s interior over its ~4.5 Gyr lifetime and assess the volatiles released from the starting material as it is heated.
Methods: The composition of Murchison (a CM chondrite) was chosen to represent the silicate material that accreted to form Europa because the CMs: formed close to early Jupiter (unlike the CIs [4]), contain sufficient water (largely held within hydrated silicates [5]), and can produce fluid compositions consistent with salts observed on Europa’s surface [2, 6]. A 1-dimensional thermal evolution code was used to model the temperatures achieved within Europa’s interior [3]. Temperature-depth profiles were then extracted at two points in time to reflect the formation of the proto-ocean (i.e. ~1600 Myr since the calcium-aluminium-rich inclusions (CAIs)) and the current-day ocean (~4568 Myr since the CAIs). Rcrust [7] and Perple_X [8] were used to predict the electrolytic fluid speciation from the starting material when heated to the temperatures predicted by the first temperature-depth profile (Stage 1; 4 – ~1600 Myr) and then the second (Stage 2; ~1600 – ~4568 Myr). Pyrrhotite was extracted from the starting material past the Fe-FeS eutectic temperature (which was also calculated using Rcrust and Perple_X) to approximate core formation. The volatiles forming the proto-ocean (i.e. those released in Stage 1) were then equilibrated using CHIM-XPT [9], where supersaturated gases were exsolved and minerals precipitated. The further volatiles (i.e. those released in Stage 2) were then added to the proto-ocean in CHIM-XPT, forming the current-day ocean.
Results and Discussion: Released volatiles for the proto-ocean are predicted to form a ~77.9 km deep layer around Europa. With the addition of the further volatiles, the current-day ocean would be ~84.8 km deep. The extraction of pyrrhotite, which occurs after proto-ocean formation, would form a metallic core of ~271.5 km radius by the current day. The current-day ocean depth and core radius predicted here agree with those inferred for current-day Europa based on observations [3]. The model predicts that both the proto- and current-day oceans would be rich in Na+, Cl-, and CO32-, which may explain the recent observation of NaCl and CO2 in geologically-disrupted regions of Europa’s surface [10, 11]. Large concentrations of NH3 and NH4+ are predicted for both the proto- and current-day oceans, despite the lack of any clear detection of nitrogen species on the surface. However, this abundance may be explained by the absence of thermodynamic data for solid nitrogen-bearing phases in the model resulting in an overestimation of nitrogen release during metamorphism (mainly as NH3). A key difference between the proto- and current-day oceans is their HS- concentration, where the current-day ocean has only ~0.2% that of the proto-ocean. This is due to the addition of the iron-rich Stage 2 volatiles to the proto-ocean causing the precipitation of pyrite (removing HS- from solution).
Conclusion: We find that Europa’s ocean composition would have varied over time as a result of continued prograde metamorphism, with particular changes in HS- concentration. The significant decrease in HS- content could affect the potential for energy generation by sulfide-oxidising microbes in the current-day ocean and, thus, would have implications for Europa’s continuous habitability.
References: [1] Běhounková M. et al. (2021) Geophys. Res. Lett., 48. [2] Melwani Daswani M. et al. (2021) Geophys. Res. Lett., 48. [3] Trinh K. T. et al. (2023) Sci. Adv., 9, eadf3955. [4] Desch S. J. et al. (2018), ApJS. 238, 11. [5] Howard K. T. et al. (2011) Geochim. Cosmochim. Acta., 75, 2735–2751. [6] Fanale F. P. et al. (2001) J. Geophys. Res., 106, 14595–14600. [7] Mayne M. J. et al. (2016), J. Metamorph. Geol., 34, 663–682. [8] Connolly J. A. D. (2005) Earth Planet. Sci. Lett., 236, 524–541. [9] Reed M. H. et al. (2010) J. Chem. Inf. Model., 53, 1689–1699. [10] Trumbo S. K. et al. (2019) Sci. Adv., 5, eaaw7123. [11] Villanueva G. L. et al. (2023) Science., 381, 1305–1308.
Part of this work was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract to the National Aeronautics and Space Administration
Implementation of genomic surveillance of SARS-CoV-2 in the Caribbean: Lessons learned for sustainability in resource-limited settings
The COVID-19 pandemic highlighted the importance of global genomic surveillance to monitor the emergence and spread of SARS-CoV-2 variants and inform public health decision-making. Until December 2020 there was minimal capacity for viral genomic surveillance in most Caribbean countries. To overcome this constraint, the COVID-19: Infectious disease Molecular epidemiology for PAthogen Control & Tracking (COVID-19 IMPACT) project was implemented to establish rapid SARS-CoV-2 whole genome nanopore sequencing at The University of the West Indies (UWI) in Trinidad and Tobago (T&T) and provide needed SARS-CoV-2 sequencing services for T&T and other Caribbean Public Health Agency Member States (CMS). Using the Oxford Nanopore Technologies MinION sequencing platform and ARTIC network sequencing protocols and bioinformatics pipeline, a total of 3610 SARS-CoV-2 positive RNA samples, received from 17 CMS, were sequenced in-situ during the period December 5th 2020 to December 31st 2021. Ninety-one Pango lineages, including those of five variants of concern (VOC), were identified. Genetic analysis revealed at least 260 introductions to the CMS from other global regions. For each of the 17 CMS, the percentage of reported COVID-19 cases sequenced by the COVID-19 IMPACT laboratory ranged from 0·02% to 3·80% (median = 1·12%). Sequences submitted to GISAID by our study represented 73·3% of all SARS-CoV-2 sequences from the 17 CMS available on the database up to December 31st 2021. Increased staffing, process and infrastructural improvement over the course of the project helped reduce turnaround times for reporting to originating institutions and sequence uploads to GISAID. Insights from our genomic surveillance network in the Caribbean region directly influenced non-pharmaceutical countermeasures in the CMS countries. However, limited availability of associated surveillance and clinical data made it challenging to contextualise the observed SARS-CoV-2 diversity and evolution, highlighting the need for development of infrastructure for collecting and integrating genomic sequencing data and sample-associated metadata
Introducing an Ethics Framework for health priority-setting in South Africa on the path to universal health coverage
Background. South Africa (SA) has embarked on a process to implement universal health coverage (UHC) funded by National Health Insurance (NHI). The 2019 NHI Bill proposes creation of a health technology assessment (HTA) body to inform decisions about which interventions NHI funds will cover under UHC. In practice, HTA often relies mainly on economic evaluations of cost-effectiveness and budget impact, with less attention to the systematic, specific consideration of important social, organisational and ethical impacts of the health technology in question. In this context, the South African Values and Ethics for Universal Health Coverage (SAVE-UHC) research project recognised an opportunity to help shape the health priority-setting process by providing a way to take account of multiple, ethically relevant considerations that reflect SA values. The SAVE-UHC Research Team developed and tested an SA-specific Ethics Framework for HTA assessment and analysis.Objectives. To develop and test an Ethics Framework for use in the SA context for health priority-setting.Methods. The Framework was developed iteratively by the authors and a multidisciplinary panel (18 participants) over a period of 18 months, using the principles outlined in the 2015 NHI White Paper as a starting point. The provisional Ethics Framework was then tested with multi-stakeholder simulated appraisal committees (SACs) in three provinces. The membership of each SAC roughly reflected the composition of a potential SA HTA committee. The deliberations and dedicated focus group discussions after each SAC meeting were recorded, analysed and used to refine the Framework, which was presented to the Working Group for review, comment and final approval.Results. This article describes the 12 domains of the Framework. The first four (Burden of the Health Condition, Expected Health Benefits and Harms, Cost-Effectiveness Analysis, and Budget Impact) are commonly used in HTA assessments, and a further eight cover the other ethical domains. These are Equity, Respect and Dignity, Impacts on Personal Financial Situation, Forming and Maintaining Important Personal Relationships, Ease of Suffering, Impact on Safety and Security, Solidarity and Social Cohesion, and Systems Factors and Constraints. In each domain are questions and prompts to enable use of the Framework by both analysts and assessors. Issues that arose, such as weighting of the domains and the availability of SA evidence, were discussed by the SACs.Conclusions. The Ethics Framework is intended for use in priority-setting within an HTA process. The Framework was well accepted by a diverse group of stakeholders. The final version will be a useful tool not only for HTA and other priority-setting processes in SA, but also for future efforts to create HTA methods in SA and elsewhere
Rethinking place-making: aligning placeness factors with perceived urban design qualities (PUDQs) to improve the built environment in historical district
Understanding the concept of place is critically important for urban design and place-making practice, and this research attempted to investigate the pathways by which perceived urban design qualities (PUDQs) influence placeness factors in the Chinese context. Twelve hypotheses were developed and combined in a structural equation model for validation. The Tanhualin historical district in Wuhan, China was selected for the analysis. As a result, place attachment was verified as a critical bridge factor that mediated the influence of PUDQs on place satisfaction. Among the five selected PUDQs, walkability and space quality were revealed as the most influential factors associated with place attachment and place satisfaction. Accessibility was actually indirectly beneficial to place-making via the mediation of walkability. Corresponding implications and strategies were discussed to maintain the sense of place for historic districts
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