Soil Metabolome Response to Whole-Ecosystem Warming at the Spruce and Peatland Responses Under Changing Environments Experiment

While peatlands have historically stored massive amounts of soil carbon, warming is expected to enhance decomposition, leading to a positive feedback with climate change. In this study, a unique whole-ecosystem warming experiment was conducted in northern Minnesota to warm peat profiles to 2 m deep while keeping water flow intact. After nearly 2 y, warming enhanced the degradation of soil organic matter and increased greenhouse gas production. Changes in organic matter quality with warming were accompanied by a stimulation of methane production relative to carbon dioxide. Our results revealed increased decomposition to be fueled by the availability of reactive carbon substrates produced by surface vegetation. The elevated rates of methanogenesis are likely to persist and exacerbate climate warming

Characterization of Ku702–NLS as Bipartite Nuclear Localization Sequence for Non-Viral Gene Delivery

Several barriers have to be overcome in order to achieve gene expression in target cells, e.g. cellular uptake, endosomal release and translocation to the nucleus. Nuclear localization sequences (NLS) enhance gene delivery by increasing the uptake of plasmid DNA (pDNA) to the nucleus. So far, only monopartite NLS were analysed for non-viral gene delivery. In this study, we examined the characteristics of a novel bipartite NLS like construct, namely NLS Ku70. We synthesized a dimeric structure of a modified NLS from the Ku70 protein (Ku702-NLS), a nuclear transport active mutant of Ku702-NLS (s1Ku702-NLS) and a nuclear transport deficient mutant of Ku702-NLS (s2Ku702). We examined the transfection efficiency of binary Ku702-NLS/DNA and ternary Ku702-NLS/PEI/DNA gene vector complexes in vitro by using standard transfection protocols as well as the magnetofection method. The application of Ku702-NLS and s1Ku702-NLS increased gene transfer efficiency in vitro and in vivo. This study shows for the first time that the use of bipartite NLS compounds alone or in combination with cationic polymers is a promising strategy to enhance the efficiency of non-viral gene transfer

Depletion of somatic mutations in splicing-associated sequences in cancer genomes

Abstract Background An important goal of cancer genomics is to identify systematically cancer-causing mutations. A common approach is to identify sites with high ratios of non-synonymous to synonymous mutations; however, if synonymous mutations are under purifying selection, this methodology leads to identification of false-positive mutations. Here, using synonymous somatic mutations (SSMs) identified in over 4000 tumours across 15 different cancer types, we sought to test this assumption by focusing on coding regions required for splicing. Results Exon flanks, which are enriched for sequences required for splicing fidelity, have ~ 17% lower SSM density compared to exonic cores, even after excluding canonical splice sites. While it is impossible to eliminate a mutation bias of unknown cause, multiple lines of evidence support a purifying selection model above a mutational bias explanation. The flank/core difference is not explained by skewed nucleotide content, replication timing, nucleosome occupancy or deficiency in mismatch repair. The depletion is not seen in tumour suppressors, consistent with their role in positive tumour selection, but is otherwise observed in cancer-associated and non-cancer genes, both essential and non-essential. Consistent with a role in splicing modulation, exonic splice enhancers have a lower SSM density before and after controlling for nucleotide composition; moreover, flanks at the 5’ end of the exons have significantly lower SSM density than at the 3’ end. Conclusions These results suggest that the observable mutational spectrum of cancer genomes is not simply a product of various mutational processes and positive selection, but might also be shaped by negative selection

Multisegmented radiation therapy as an alternative to 3D conformal radiation therapy, with special reference to breast cancer tangential fields

The paper compares the techniques of 3DCRT and MSCRT in terms of PTV coverage and doses to OARs. The study population consisted of 175 breast cancer patients in whom treatement was analysed in regard to the use of lateral and medial tangential fields. Although we have failed to establish statistical significance at the P=0.05 levelthe results look clinically promising in favour of MSCRT

Classification of chest radiographs for pneumoconiosis: a comparison of two methods of reading.

Variability between readers in the evaluation of the radiographic appearances of pneumoconiosis has been investigated by several authors. To reduce inter and intrareader variability, standard reference films were introduced for epidemiological purposes. Improved films and methods of classification were published in subsequent years. The category of profusion of small opacities is determined by considering the profusion as a whole over the affected zones of the lung, and by comparing this with the standard radiographs. This requires a mental process of integrating profusion over the affected zones. The purpose of the present study was to determine whether there would be any advantage, in terms of improved reader agreement, in reading and reporting the six lung zones separately rather than integrating all readings to produce a single classification for each film. The possible validity of evaluating the six zones separately was suggested by a previous study of the relation between radiographic appearances and underlying pathology in which a good correlation was found (kappa = 0.47, p \u3c 0.0001). An opportunity arose to investigate this question during an epidemiological study of hard rock miners in Ontario