Radioprotection of targeted and bystander cells by methylproamine

INTRODUCTION: Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells.

METHODS: T98G glioma cells were treated with 15 μM methylproamine and exposed to (137)Cs γ-ray/X-ray irradiation and He(2+) microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay.

RESULTS: Radioprotection of directly targeted T98G cells by methylproamine was observed for (137)Cs γ-rays and X-rays but not for He(2+) charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He(2+) ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed.

DISCUSSION AND CONCLUSION: Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He(2+) ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received.

SO and CS observations of molecular clouds - II. Analysis and modelling of the abundance ratios - probing O-2/CO with SO/CS?

We here analyse the observational SO and CS data presented in Nilsson ct al. (2000). The SO/CS integrated intensity ratio maps are presented for 19 molecular clouds, together with tables of relevant ratios at strategic positions, where we have also observed (SO)-S-34 and/or (CS)-S-34. The SO/CS abundance ratio as calculated from an LTE analysis is highly varying within and between the sources. Our isotopomer observations and Monte Carlo simulations verify that this is not an artifact due to optical depth problems. The variation of the maximum SO/CS abundance ratio between the clouds is 0.2-7. The largest variations within a cloud are found for the most nearby objects, possibly indicating resolution effects. We have also performed time dependent chemical simulations. We compare the simulations with our observed SO/CS abundance ratios and suggest a varying oxygen to carbon initial abundance, differing temporal evolution, density differences and X-ray sources associated with young stellar objects as possible explanations to the variations. In particular, the observed variation of the maximum SO/CS abundance ratio between the clouds can be explained by using initial O/C+ abundance ratios in the range 1.3-2.5. We finally derive a relationship between the SO/CS and O-2/CO abundance ratios, which may be used as a guide to find the most promising interstellar O-2 search targets.

Electron-impact rotational excitation of the carbon monosulphide (CS) molecule

Rotational excitation of the carbon monosulphide (CS) molecule by thermal electron-impact is studied using the molecular R-matrix method combined with the adiabatic-nuclei-rotation (ANR) approximation. Rate coefficients are obtained for electron temperatures in the range 5-5000 K and for transitions involving levels up to J = 40. It is confirmed that dipole allowed transitions (Delta J = 1) are dominant and that the corresponding rate coefficients exceed those for excitation by neutrals by at least five orders of magnitude. As a result, the present rates should be included in any detailed population model of CS in sources where the electron fraction is larger than similar to 10(-5), in particular in diffuse molecular clouds and interstellar shocks.

Nineteenth and twentieth century sea-level changes in Tasmania and New Zealand

Positive deviations from linear sea-level trends represent important climate signals if they are persistent and geographically widespread. This paper documents rapid sea-level rise reconstructed from sedimentary records obtained from salt marshes in the Southwest Pacific region (Tasmania and New Zealand). A new late Holocene relative sea-level record from eastern Tasmania was dated by AMS(14)C (conventional, high precision and bomb-spike), Cs-137, Pb-210, stable Pb isotopic ratios, trace metals, pollen and charcoal analyses. Palaeosea-level positions were determined by foraminiferal analyses. Relative sea level in Tasmania was within half a metre of present sea level for much of the last 6000 yr. Between 1900 and 1950 relative sea level rose at an average rate of 4.2 +/- 0.1 mm/yr. During the latter half of the 20th century the reconstructed rate of relative sea-level rise was 0.7 +/- 0.6 mm/yr. Our study is consistent with a similar pattern of relative sea-level change recently reconstructed for southern New Zealand. The change in the rate of sea-level rise in the SW Pacific during the early 20th century was larger than in the North Atlantic and could suggest that northern hemisphere land-based ice was the most significant melt source for global sea-level rise. (C) 2011 Elsevier B.V. All rights reserved.

Degradation of carbon disulphide (CS2) in soils and groundwater from a CS2 -contaminated site

This study is the first investigation of biodegradation of carbon disulphide (CS₂) in soil that provides estimates of degradation rates and identifies intermediate degradation products and carbon isotope signatures of degradation. Microcosm studies were undertaken under anaerobic conditions using soil and groundwater recovered from CS₂-contaminated sites. Proposed degradation mechanisms were validated using equilibrium speciation modelling of concentrations and carbon isotope ratios. A first-order degradation rate constant of 1.25 × 10-2 h-1 was obtained for biological degradation with soil. Carbonyl sulphide (COS) and hydrogen sulphide (H₂S) were found to be intermediates of degradation, but did not accumulate in vials. A 13C/12C enrichment factor of -7.5 ± 0.8 ‰ was obtained for degradation within microcosms with both soil and groundwater whereas a 13C/12C enrichment factor of -23.0 ± 2.1 ‰ was obtained for degradation with site groundwater alone. It can be concluded that biological degradation of both CS2-contaminated soil and groundwater is likely to occur in the field suggesting that natural attenuation may be an appropriate remedial tool at some sites. The presence of biodegradation by-products including COS and H₂S indicates that biodegradation of CS₂ is occurring and stable carbon isotopes are a promising tool to quantify CS₂ degradation.

The role of lipids and protein kinase Cs in the pathogenesis of diabetic retinopathy

Diabetic retinopathy is one of the most common complications of diabetes and is a major cause of new blindness in the working-age population of developed countries. While the exact pathogenic basis of this condition remains ill defined, it is clear that hyperglycaemia is a critical factor in its aetiology. Protein kinase C (PKC) activation is one of the sequelae of hyperglycaemia and it is thought to play an important role in the development of diabetic complications. This review questions the currently held dogma that PKC stimulation in diabetes is solely mediated through the overproduction of palmitate and oleate enriched diacylglycerols. Blood glucose concentrations are closely tracked by changes in the levels of free fatty acids and these, in addition to oxidative stress, may account for the aberrant activation of PKCs in diabetes. Little is known about why PKCs fail to downregulate in diabetes and efforts should be directed towards acquiring such information. Considerable evidence implicates the PKCbeta isoform in the pathogenesis of diabetic retinopathy, but other isoforms may also be of relevance. In addition to PKCs, it is evident that novel diacyglycerol-activated non-kinase receptors could also play a role in the development of diabetic complications. Therapeutic agents have been developed to inhibit specific PKC isoforms and PKCbeta antagonists are currently undergoing clinical trials to test their toxicity and efficacy in suppressing diabetic complications. The likely impact of these drugs in the treatment of diabetic patients is considered.

Mood congruent psychotic symptoms and specific cognitive deficits in carriers of the novel schizophrenia risk variant at MIR-137

Objective: The Schizophrenia Psychiatric Genome-wide Association (GWAS) Consortium recently reported on five novel schizophrenia susceptibility loci. The most significant finding mapped to a micro-RNA, MIR-137, which may be involved in regulating the function of other schizophrenia and bipolar disorder susceptibility genes. Method: We genotyped 821 patients with confirmed DSM-IV diagnoses of schizophrenia, bipolar affective disorder I and schizoaffective disorder for the risk SNP (rs1625579) and investigated the clinical profiles of risk allele carriers using a within-case design. We also assessed neurocognitive performance in a subset of cases (n=399) and controls (n=171). Results: Carriers of the risk allele had lower scores for an OPCRIT-derived positive symptom factor (p=0.04) and lower scores on a lifetime measure of psychosis incongruity (p=0.017). Risk allele carriers also had more cognitive deficits involving episodic memory and attentional control. Conclusion: This is the first evidence that the MIR-137 risk variant may be associated with a specific subgroup of psychosis patients. Although the effect of this single SNP was not clinically relevant, investigation of the impact of carrying multiple risk SNPs in the MIR-137 regulatory network on diagnosis and illness profile may be warranted. © 2012 Elsevier Ireland Ltd.