A mutation in POLE predisposing to a multi-tumour phenotype

Somatic mutations in the POLE gene encoding the catalytic subunit of DNA polymerase epsilon have been found in sporadic colorectal cancers (CRCs) and are most likely of importance in tumour development and/or progression. Recently, families with dominantly inherited colorectal adenomas and colorectal cancer were shown to have a causative heterozygous germline mutation in the proofreading exonuclease domain of POLE. The highly penetrant mutation was associated with predisposition to CRC only and no extra-colonic tumours were observed. We have identified a mutation in a large family in which the carriers not only developed CRC, they also demonstrate a highly penetrant predisposition to extra-intestinal tumours such as ovarian, endometrial and brain tumours. The mutation, NM_006231.2:c.1089C>A, p.Asn363Lys, also located in the proofreading exonuclease domain is directly involved in DNA binding. Theoretical prediction of the amino acid substitution suggests a profound effect of the substrate binding capability and a more severe impairment of the catalytic activity compared to the previously reported germline mutation. A possible genotype to phenotype correlation for deleterious mutations in POLE might exist that needs to be considered in the follow-up of mutation carriers

Chemical pulping: the influence of the molecular weight of added xylan on pulp properties

The aim of this study was to investigate if added beech xylan with low molecule weight (Mw) could penetrate into the fiber wall to a greater extent compared to xylan with high Mw. The high Mw (ca 11000) xylan was degraded using enzymes to obtain xylan with low Mw (ca 1800). The influence from the added xylan on the strength properties was evaluated. The cooks in this study were performed without mechanical damage introduced during the cooking process, thus any conclusions of the impact from adding low Mw xylan on the sensitivity towards mechanical damage was not possible. The different microscopy analyses performed could not show any evidence for a higher penetration of xylan into the fiber wall when producing the pulp with addition of low molecular weight (low Mw) xylan. The low Mw xylan did not contribute to any improved pulp properties, rather the opposite. Addition of low Mw-xylan did not result in straighter fibers compared to the Ref-pulp, which was the case for the high Mw-xylan-pulp. The tensile indexdevelopment (tensile vs PFI-beating and tensile vs density) for the low Mw-pulp was even worse compared to the Ref-pulp. The pulp produced with addition of the high Mw-xylan showed, as earlier seen, an improved tensile index development compared to the Ref-pul

CRUW chemical pulping sub-project 1: the influence of xylan on the sensitivity towards fiber damage

The aim of this study was to determine if the presence and position of xylan in the fiber wall are of importance for the degree of damage introduced into fibers during mechanical action in the cook. Kraft pulps from spruce with different amounts of xylan have been produced in the laboratory, either by adding birch xylan in different positions in the cook or by redistribution of spruce xylan. At the end of the cook, fiber damages were introduced by subjecting the fibers to shear and compression forces. The extra birch xylan had adsorbed on the fiber surfaces, the outer fiber walls (presumably S1/primary wall) as well as on the fiber cell lumen wall. Xylan penetration into the fiber wall was very low. A large variation in coverage of surface xylan within the fibers and between fibers was noted. No significant difference between pulps produced in the different ways or between the pulps produced with or without mechanical treatment could however be observed. The extra xylan added resulted as expected in an improved tensile strength development for these pulps. No direct indications were seen that the extra xylan added during the cook resulted in a lower amount of introduced damaged areas. But some positive tendencies could be noted for the pulps produced with extra xylan added including: a lower kink/mm and lower amount of cleavage/fiber measured by the HCL method; and the zero-span level and tear-tensile relationship were not inferior compared to the reference despite the higher xylan content. The removal and subsequent re-introduction of xylan into the cook seemed to negatively influence the strength properties, i.e. the tear-tensile relationship was inferior compared to the reference pulp. The redistribution procedure may have drained the fiber wall of xylan negatively influencing the strength propertie