Preclinical Detection of Variant CJD and BSE Prions in Blood

The emergence of variant Creutzfeldt Jakob Disease (vCJD) is considered a likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy (BSE) agent. More recently, secondary vCJD cases were identified in patients transfused with blood products prepared from apparently healthy donors who later went on to develop the disease. As there is no validated assay for detection of vCJD/BSE infected individuals the prevalence of the disease in the population remains uncertain. In that context, the risk of vCJD blood borne transmission is considered as a serious concern by health authorities. In this study, appropriate conditions and substrates for highly efficient and specific in vitro amplification of vCJD/BSE agent using Protein Misfolding Cyclic Amplification (PMCA) were first identified. This showed that whatever the origin (species) of the vCJD/BSE agent, the ovine Q₁₇₁ PrP substrates provided the best amplification performances. These results indicate that the homology of PrP amino-acid sequence between the seed and the substrate is not the crucial determinant of the vCJD agent propagation in vitro. The ability of this method to detect endogenous vCJD/BSE agent in the blood was then defined. In both sheep and primate models of the disease, the assay enabled the identification of infected individuals in the early preclinical stage of the incubation period. Finally, sample panels that included buffy coat from vCJD affected patients and healthy controls were tested blind. The assay identified three out of the four tested vCJD affected patients and no false positive was observed in 141 healthy controls. The negative results observed in one of the tested vCJD cases concurs with results reported by others using a different vCJD agent blood detection assay and raises the question of the potential absence of prionemia in certain patients.     

The chemokine receptors ACKR2 and CCR2 reciprocally regulate lymphatic vessel density

Macrophages regulate lymphatic vasculature development; however, the molecular mechanisms regulating their recruitment to developing, and adult, lymphatic vascular sites are not known. Here, we report that resting mice deficient for the inflammatory chemokine‐scavenging receptor, ACKR2, display increased lymphatic vessel density in a range of tissues under resting and regenerating conditions. This appears not to alter dendritic cell migration to draining lymph nodes but is associated with enhanced fluid drainage from peripheral tissues and thus with a hypotensive phenotype. Examination of embryonic skin revealed that this lymphatic vessel density phenotype is developmentally established. Further studies indicated that macrophages and the inflammatory CC‐chemokine CCL2, which is scavenged by ACKR2, are associated with this phenotype. Accordingly, mice deficient for the CCL2 signalling receptor, CCR2, displayed a reciprocal phenotype of reduced lymphatic vessel density. Further examination revealed that proximity of pro‐lymphangiogenic macrophages to developing lymphatic vessel surfaces is increased in ACKR2‐deficient mice and reduced in CCR2‐deficient mice. Therefore, these receptors regulate vessel density by reciprocally modulating pro‐lymphangiogenic macrophage recruitment, and proximity, to developing, resting and regenerating lymphatic vessels.     

Variation and inheritance of iron reductase activity in the roots of common bean (<Emphasis Type="Italic">Phaseolus vulgaris</Emphasis> L.) and association with seed iron accumulation QTL

Background  

Iron deficiency anemia is a global problem which often affects women and children of developing countries. Strategy I plants, such as common bean (Phaseolus vulgaris L.) take up iron through a process that involves an iron reduction mechanism in their roots; this reduction is required to convert ferric iron to ferrous iron. Root absorbed iron is critical for the iron nutrition of the plant, and for the delivery of iron to the shoot and ultimately the seeds. The objectives of this study were to determine the variability and inheritance for iron reductase activity in a range of genotypes and in a low × high seed iron cross (DOR364 × G19833), to identify quantitative trait loci (QTL) for this trait, and to assess possible associations with seed iron levels.     

Aluminium in aquatic environments: abundance and ecotoxicological impacts

Aquatic Ecology - Aluminium (Al) is a common chemical element released into the aquatic environment from the Earth’s crust and many anthropogenic activities. It may be present in various...     

Gene conversions in the horse alpha-globin gene complex

The sequences of the linked alpha 2- and alpha 1-globin genes of the equine BI and BII haplotypes are greater than 99% identical within a 1.2-kb region extending from approximately 75 bp upstream of the putative cap site to a point approximately 150 bp 3' to the poly A addition signal. Differences between the alpha 2 and alpha 1 genes that are common to both haplotypes indicate that a major gene conversion occurred approximately 12 Myr ago and that this has been followed by shorter, more localized, conversions. Interhaplotype (allelic) comparisons at the alpha loci suggest that the BI and BII haplotypes have probably existed independently greater than or equal to 0.5 Myr and that the alpha 1 genes may have undergone a recent interchromosomal gene conversion.