Characterisation of physico-mechanical properties and degradation potential of calcium alginate beads for use in embolisation

High molecular weight alginate beads with 59% mannuronic acid content or 68% guluronic acid were prepared using a droplet generator and crosslinked in calcium chloride. The alginate beads were compared to current embolisation microspheres for compressibility and monitored over 12 weeks for size and weight change at 37°C in low volumes of ringers solutions. A sheep uterine model was used to analyse bead degradation and inflammatory response over 12 weeks. Both the in vitro and in vivo data show good delivery, with a compressibility similar to current embolic beads. In vitro, swelling was noted almost immediately and after 12 weeks the first signs of degradation were noted. No difference was noted in vivo. This study has shown that high molecular weight alginate gel beads were well tolerated by the body, but beads associated with induced thrombi were susceptible to inflammatory cell infiltration. The beads were shown to be easy to handle and were still observable after 3 months in vivo. The beads were robust enough to be delivered through a 2.7 Fr microcatheter. This study has demonstrated that high molecular weight, high purity alginate bead can be considered as semi-permanent embolisation beads, with the potential to bioresorb over time

Mutational analysis and genotype/phenotype correlation in Turkish Charcot-Marie-Tooth Type I and HNPP patients

The major Charcot-Marie-Tooth Type 1 (CMT1) locus, CMT1A, and Hereditary neuropathy with liability to pressure palsies (HNPP) cosegregate with a 1.5-Mb duplication and a 1.5-Mb deletion, respectively, in band 17p11.2. Point mutations in peripheral myelin gene 22 (PMP22), myelin protein zero (MPZ), and connexin 32 (Cx32) have been reported in CMT1, and in PMP22 in HNPP patients without deletion. We have screened 54 CMT1 patients, of variable clinical severity, and 25 HNPP patients from Turkey, with no duplication or deletion, for mutations in the PMP22 and Cx32 genes. A novel frameshift mutation affecting the second extracellular domain of PMP22 was found in an HNPP patient, while a point mutation in the second transmembrane domain of the protein was detected in a CMT1 patient. Two point mutations affecting different domains of Cx32 were identified in two CMTX patients. Another patient was found to carry a polymorphism in a non-conserved codon of the Cx32 gene. The clinical phenotypes of the patients correlate well with the effect of the mutation on the protein

A large-scale RNAi screen identifies LCMR1 as a critical regulator of Tspan8-mediated melanoma invasion

International audienc

The influence of evolutionary distance between cross-species microsatellites and primer base-pair composition on allelic dropout rates

Allelic dropouts (ADO) are an important source of genotyping error and because of their negative impact on non-invasive sampling techniques, have become the focus of considerable attention. Previous studies have noted that ADO rates are greater with increasing allele size and in tetranucleotides. It has also been suggested, but not tested, that ADO rates may be higher in studies using crossspecies microsatellites and that mutations may play a role in ADO rates. Here we examine the relationship between ADO rates and the relationship between evolutionary distance since divergence time between species for which the microsatellite was designed for and species on which it was used (divergence times), and how this may interact with median allele size. In addition, as the adenosine (A) and thymine (T) content of the primer may increase mutation rates, we also included total % AT content of the primer in the analyses. Finally, we examined whether other commonly associated causes of ADO (i.e. repeat motif length, median allele size and allele number) co-varied. We found that ADO rates were positively associated to divergence time and median allele size. Repeat motif length, median allele size and allele number positively covaried suggesting a link between mutability and these parameters. Results from previous studies that did not correct for co-variation among these parameters may have been confounded. AT content of the primer was positively associated with ADO rates. The best linear regression model contained divergence time, median allele size and total % AT content, explaining 21% of the variation in ADO rates. The available evidence suggests that mutations partly cause ADO and that studies using cross-species microsatellites may be at higher risk of ADO. Based on our results we highlight some important considerations in the selection of microsatellites for all conservation genetic studies