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

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

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

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

Characterisation of dust emissions from machined engineered stones to understand the hazard for accelerated silicosis

Engineered stones are novel construction materials associated with a recent upsurge in silicosis cases among workers in the stonemason industry. In order to understand the hazard for the short latency of lung disease among stonemasons, we simulated real-time dust exposure scenario by dry-machining engineered stones in controlled conditions, capturing and analysing the respirable dust generated for physical and chemical characteristics. Natural granite and marble were included for comparison. Cutting engineered stones generated high concentrations of very fine particles ( 80% respirable crystalline silica content, in the form of quartz and cristobalite. Engineered stones also contained 8–20% resin and 1–8% by weight metal elements. In comparison, natural stones had far lower respirable crystalline silica (4- 30%) and much higher metal content, 29–37%. Natural stone dust emissions also had a smaller surface area than engineered stone, as well as lower surface charge. This study highlighted the physical and chemical variability within engineered stone types as well as between engineered and natural stones. This information will ultimately help understand the unique hazard posed by engineered stone fabrication work and help guide the development of specific engineering control measures targeting lower exposure to respirable crystalline silica.Chandnee Ramkissoon, Sharyn Gaskin, Leigh Thredgold, Tony Hall, Shelley Rowett, Richard Gu

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

Clinical multiplexed exome sequencing distinguishes adult oligodendroglial neoplasms from astrocytic and mixed lineage gliomas

Classifying adult gliomas remains largely a histologic diagnosis based on morphology; however astrocytic, oligodendroglial and mixed lineage tumors can display overlapping histologic features. We used multiplexed exome sequencing (OncoPanel) on 108 primary or recurrent adult gliomas, comprising 65 oligodendrogliomas, 28 astrocytomas and 15 mixed oligoastrocytomas to identify lesions that could enhance lineage classification. Mutations in TP53 (20/28, 71%) and ATRX (15/28, 54%) were enriched in astrocytic tumors compared to oligodendroglial tumors of which 4/65 (6%) had mutations in TP53 and 2/65 (3%) had ATRX mutations. We found that oligoastrocytomas harbored mutations in TP53 (80%, 12/15) and ATRX (60%, 9/15) at frequencies similar to pure astrocytic tumors, suggesting that oligoastrocytomas and astrocytomas may represent a single genetic or biological entity. p53 protein expression correlated with mutation status and showed significant increases in astrocytomas and oligoastrocytomas compared to oligodendrogliomas, a finding that also may facilitate accurate classification. Furthermore our OncoPanel analysis revealed that 15% of IDH1/2 mutant gliomas would not be detected by traditional IDH1 (p.R132H) antibody testing, supporting the use of genomic technologies in providing clinically relevant data. In all, our results demonstrate that multiplexed exome sequencing can support evaluation and classification of adult low-grade gliomas with a single clinical test

A sensitive non-radioactive northern blot method to detect small RNAs

The continuing discoveries of potentially active small RNAs at an unprecedented rate using high-throughput sequencing have raised the need for methods that can reliably detect and quantitate the expression levels of small RNAs. Currently, northern blot is the most widely used method for validating small RNAs that are identified by methods such as high-throughput sequencing. We describe a new northern blot-based protocol (LED) for small RNA (∼15–40 bases) detection using digoxigenin (DIG)-labeled oligonucleotide probes containing locked nucleic acids (LNA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide for cross-linking the RNA to the membrane. LED generates clearly visible signals for RNA amounts as low as 0.05 fmol. This method requires as little as a few seconds of membrane exposure to outperform the signal intensity using overnight exposure of isotope-based methods, corresponding to ∼1000-fold improvement in exposure-time. In contrast to commonly used radioisotope-based methods, which require freshly prepared and hazardous probes, LED probes can be stored for at least 6 months, facilitate faster and more cost-effective experiments, and are more environmentally friendly. A detailed protocol of LED is provided in the Supplementary Data

A genetic case-control study confirms the implication of SMAD7 and TNF locus in the development of proliferative vitreoretinopathy

PURPOSE: Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (RD) surgery and although the risk for developing this complication is associated with some clinical characteristics, the correlation is far from absolute, raising the possibility of genetic susceptibility. The objective of this study was to analyze the genetic contribution to PVR in patients undergoing RD surgery, the Retina 4 Project. METHODS: A candidate gene association study was conducted in 2006 in a Spanish population of 450 patients suffering from primary rhegmatogenous RD. Replication was carried out in a larger population undergoing RD surgery at several European centers among 546 new patients. Single nucleotide polymorphism (SNP) of 30 genes known to be involved with inflammation were analyzed. For replication stage, those genes previously detected as significantly associated with PVR were genotyped. Distribution of allelic and haplotypic frequencies in case and control group were analyzed. Single and haplotypic analysis were assessed. The Rosenberg two-stage method was used to correct for single and multiple analyses. RESULTS: After correction for multiple comparisons, four genes were significantly associated with PVR: SMAD7 (P = 0.004), PIK3CG (P = 0.009), TNF locus (P = 0.0005), and TNFR2 (P = 0.019) In the European sample, replication was observed in SMAD7 (P = 0.047) and the TNF locus (P = 0.044). CONCLUSIONS: These results confirm the genetic contribution to PVR and the implication of SMAD7 and TNF locus in the development of PVR. This finding may have implications for understanding the mechanisms of PVR and could provide a potential new therapeutic target for PVR prophylaxis