Simulating the Martian Chemical Enivronment

We report on new analogue materials to simulate Martian rocks and soils, especially under realistic redox conditions

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

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

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

MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME)

Chronic Fatigue Syndrome (CFS/ME) is a complex multisystem disease of unknown aetiology which causes debilitating symptoms in up to 1% of the global population. Although a large cohort of genes have been shown to exhibit altered expression in CFS/ME patients, it is currently unknown whether microRNA (miRNA) molecules which regulate gene translation contribute to disease pathogenesis. We hypothesized that changes in microRNA expression in patient leukocytes contribute to CFS/ME pathology, and may therefore represent useful diagnostic biomarkers that can be detected in the peripheral blood of CFS/ME patients.miRNA expression in peripheral blood mononuclear cells (PBMC) from CFS/ME patients and healthy controls was analysed using the Ambion Bioarray V1. miRNA demonstrating differential expression were validated by qRT-PCR and then replicated in fractionated blood leukocyte subsets from an independent patient cohort. The CFS/ME associated miRNA identified by these experiments were then transfected into primary NK cells and gene expression analyses conducted to identify their gene targets.Microarray analysis identified differential expression of 34 miRNA, all of which were up-regulated. Four of the 34 miRNA had confirmed expression changes by qRT-PCR. Fractionating PBMC samples by cell type from an independent patient cohort identified changes in miRNA expression in NK-cells, B-cells and monocytes with the most significant abnormalities occurring in NK cells. Transfecting primary NK cells with hsa-miR-99b or hsa-miR-330-3p, resulted in gene expression changes consistent with NK cell activation but diminished cytotoxicity, suggesting that defective NK cell function contributes to CFS/ME pathology.This study demonstrates altered microRNA expression in the peripheral blood mononuclear cells of CFS/ME patients, which are potential diagnostic biomarkers. The greatest degree of miRNA deregulation was identified in NK cells with targets consistent with cellular activation and altered effector function

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

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

Clostridium septicum sepsis and colorectal cancer - a reminder

<p>Abstract</p> <p>Background</p> <p>Spontaneous clostridium septicum infections are rare and are associated with a high mortality. Association of clostridium infection with colorectal malignancies have been previously reported and most cases are described in tumours of the ascending colon. We report our experience of clostridium septicum infection in the presence of tumour perforation in a series of two patients as a reminder of its association with sepsis in the presence of colorectal malignancy.</p> <p>Case Presentation</p> <p>We isolated clostridium septicum infection in a series of two patients admitted as emergencies. One patient was found to have a perforated caecal tumour intraoperatively whilst the other had a perforated rectal tumour. The clinical outcome and management of each case are reported and underlying reasons for variations in outcome are discussed.</p> <p>Conclusion</p> <p>Although uncomman, the possibility of clostridium septicum sepsis should be borne in mind in patients who present with underlying malignancy and have sepsis. The cumulative effect of sepsis and malignant perforation is associated with a high morbidity and mortality. Awareness and early diagnosis of clostridium septicum may improve the prognosis of what is usually regarded as a fatal infection.</p

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

Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663

<p>Abstract</p> <p>Background</p> <p>Differentiation of the acute myeloid leukemia (AML) cell line HL-60 can be induced by all trans-retinoic acid (ATRA); however, the mechanism regulating this process has not been fully characterized.</p> <p>Methods</p> <p>Using bioinformatics and <it>in vitro </it>experiments, we identified the microRNA gene expression profile of HL-60 cells during ATRA induced granulocytic differentiation.</p> <p>Results</p> <p>Six microRNAs were upregulated by ATRA treatment, miR-663, miR-494, miR-145, miR-22, miR-363* and miR-223; and three microRNAs were downregulated, miR-10a, miR-181 and miR-612. Additionally, miR-663 expression was regulated by ATRA. We used a lentivirus (LV) backbone incorporating the spleen focus forming virus (SFFV-F) promoter to drive miR-663 expression, as the CMV (Cytomegalovirus) promoter is ineffective in some lymphocyte cells. Transfection of LV-miR-663 induced significant HL-60 cell differentiation <it>in vitro</it>.</p> <p>Conclusions</p> <p>Our results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies</p