Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases

Peritoneal metastases (PMs) from colorectal cancer (CRC) respond poorly to treatment and are associated with unfavorable prognosis. For example, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery in resectable patients shows limited benefit, and novel treatments are urgently needed. The majority of CRC-PMs represent the CMS4 molecular subtype of CRC, and here we queried the vulnerabilities of this subtype in pharmacogenomic databases to identify novel therapies. This reveals the copper ionophore elesclomol (ES) as highly effective against CRC-PMs. ES exhibits rapid cytotoxicity against CMS4 cells by targeting mitochondria. We find that a markedly reduced mitochondrial content in CMS4 cells explains their vulnerability to ES. ES demonstrates efficacy in preclinical models of PMs, including CRC-PMs and ovarian cancer organoids, mouse models, and a HIPEC rat model of PMs. The above proposes ES as a promising candidate for the local treatment of CRC-PMs, with broader implications for other PM-prone cancers

Thermal, mechanical, and surface properties of poly(2-N-alkyl-2-oxazoline)s

Thermal, mechanical, and surface properties of a library of poly(2-oxazoline)s are investigated. These polymers are suitable to study structure/property relationships as their cationic ROP and the relative facile monomer synthesis allow for control over the molecular structure. The number of carbon atoms in the linear side-chain is systematically varied from methyl to nonyl. Relations between chemical structures, thermal transitions, surface energies, and elastic moduli are discussed. It is shown that the mechanical and thermal properties of the polymers depend on the presence of a crystalline phase in the material. The amorphous polymers reveal a decrease in the reduced moduli along with a decrease in their respective glass transition temperature with increasing length of the side-chain

Water uptake of poly(2-N-alkyl-2-oxazoline)s : influence of crystallinity and hydrogen-bonding on the mechanical properties

Poly(2-oxazoline)s are suitable materials to study structure-property relationships as their preparation by a living cationic ring-opening polymerization procedure and the relatively facile monomer synthesis allow accurate control over the molecular structure. In this contribution, the number of carbon atoms in the linear side-chain is systematically varied from a short methyl-to a long nonyl-group. As some of the materials are known to be hygroscopic, the effect of water uptake on the mechanical properties is investigated in detail. The combination of water uptake measurements, FT-IR spectroscopy and indentation revealed that only the samples with very short side-chains show significant hygroscopicity, while samples with longer side-chains exhibit crystalline behavior. Furthermore, depending on the polymer structure, it could be differentiated between side-chain and main-chain crystallinity

Corrigendum: PolymapR - Linkage analysis and genetic map construction from F 1 populations of outcrossing polyploids

In the original article, there was an incorrect formula. The formula appears in section 2.2.2, 'Linkage analysis in the presence of preferential chromosomal pairing', on page 3498. The correct formula is below in the context in which it appears. This gives rise to the likelihood function (Formula Presented) , which when solved leads to the following maximumlikelihood estimate for (Formula Presented). This has been corrected</p

PolymapR-linkage analysis and genetic map construction from F1 populations of outcrossing polyploids

Motivation: Polyploid species carry more than two copies of each chromosome, a condition found in many of the world's most important crops. Genetic mapping in polyploids is more complex than in diploid species, resulting in a lack of available software tools. These are needed if we are to realize all the opportunities offered by modern genotyping platforms for genetic research and breeding in polyploid crops.Results: polymapR is an R package for genetic linkage analysis and integrated genetic map construction from bi-parental populations of outcrossing autopolyploids. It can currently analyse triploid, tetraploid and hexaploid marker datasets and is applicable to various crops including potato, leek, alfalfa, blueberry, chrysanthemum, sweet potato or kiwifruit. It can detect, estimate and correct for preferential chromosome pairing, and has been tested on high-density marker datasets from potato, rose and chrysanthemum, generating high-density integrated linkage maps in all of these crops.Availability and implementation: polymapR is freely available under the general public license from the Comprehensive R Archive Network (CRAN) at http://cran.r-project.org/package=polymapR.Supplementary information: Supplementary data are available at Bioinformatics online.</p

Joint analysis of deposition fluxes and atmospheric concentrations of inorganic nitrogen and sulphur compounds predicted by six chemistry transport models in the frame of the EURODELTAIII project

In the framework of the UNECE Task Force on Measurement and Modelling (TFMM) under the Convention on Long-range Transboundary Air Pollution (LRTAP), the EURODELTAIII project is evaluating how well air quality models are able to reproduce observed pollutant air concentrations and deposition fluxes in Europe. In this paper the sulphur and nitrogen deposition estimates of six state-of-the-art regional models (CAMx, CHIMERE, EMEP MSC-W, LOTOS-EUROS, MINNI and CMAQ) are evaluated and compared for four intensive EMEP measurement periods (25 Feb–26 Mar 2009; 17 Sep–15 Oct 2008; 8 Jan–4 Feb 2007 and 1–30 Jun 2006). For sulphur, this study shows the importance of including sea salt sulphate emissions for obtaining better model results; CMAQ, the only model considering these emissions in its formulation, was the only model able to reproduce the high measured values of wet deposition of sulphur at coastal sites. MINNI and LOTOS-EUROS underestimate sulphate wet deposition for all periods and have low wet deposition efficiency for sulphur. For reduced nitrogen, all the models underestimate both wet deposition and total air concentrations (ammonia plus ammonium) in the summer campaign, highlighting a potential lack of emissions (or incoming fluxes) in this period. In the rest of campaigns there is a general underestimation of wet deposition by all models (MINNI and CMAQ with the highest negative bias), with the exception of EMEP, which underestimates the least and even overestimates deposition in two campaigns. This model has higher scavenging deposition efficiency for the aerosol component, which seems to partly explain the different behaviour of the models. For oxidized nitrogen, CMAQ, CAMx and MINNI predict the lowest wet deposition and the highest total air concentrations (nitric acid plus nitrates). Comparison with observations indicates a general underestimation of wet oxidized nitrogen deposition by these models, as well as an overestimation of total air concentration for all the campaigns, except for the 2006 campaign. This points to a low efficiency in the wet deposition of oxidized nitrogen for these models, especially with regards to the scavenging of nitric acid, which is the main driver of oxidized N deposition for all the models. CHIMERE, LOTOS-EUROS and EMEP agree better with the observations for both wet deposition and air concentration of oxidized nitrogen, although CHIMERE seems to overestimate wet deposition in the summer period. This requires further investigation, as the gas-particle equilibrium seems to be biased towards the gas phase (nitric acid) for this model. In the case of MINNI, the frequent underestimation of wet deposition combined with an overestimation of atmospheric concentrations for the three pollutants indicates a low efficiency of the wet deposition processes. This can be due to several reasons, such as an underestimation of scavenging ratios, large vertical concentration gradients (resulting in small concentrations at cloud height) or a poor parameterization of clouds. Large differences between models were also found for the estimates of dry deposition. However, the lack of suitable measurements makes it impossible to assess model performance for this process. These uncertainties should be addressed in future research, since dry deposition contributes significantly to the total deposition for the three deposited species, with values in the same range as wet deposition for most of the models, and with even higher values for some of them, especially for reduced nitrogen