A novel technique for retrospective genetic analysis of the response to vaccination or infection using cell-free DNA from archived sheep serum and plasma

Genetic variation is associated with differences in disease resistance and susceptibility among individuals within a population. To date, molecular genetic analyses of host responses have relied on extraction of genomic DNA from whole blood or tissue samples. However, such samples are not routinely collected during large-scale field studies. We demonstrate that cell-free genomic DNA (cfDNA) may be extracted and amplified from archived plasma samples, allowing retrospective analysis of host genetic diversity. This technique was also applicable to archived serum samples up to 35 years old and to different ruminant species. As proof of concept, we used this cfDNA approach to genotype the major histocompatibility complex (MHC) class II DRB1 locus of 224 Merino sheep which had participated in field trials of a commercial Haemonchus contortus vaccine, Barbervax®, in Australia. This identified a total of 51 different DRB1 alleles and their relative frequencies. This is the first study to examine host MHC diversity using DNA extracted from archived plasma samples, an approach that may be applied to retrospective analyses of genetic diversity and responses to vaccination or infection across different species and populations

An exact solution of the moving boundary problem for the relativistic plasma expansion in a dipole magnetic field

An exact analytic solution is obtained for a uniformly expanding, neutral, highly conducting plasma sphere in an ambient dipole magnetic field with an arbitrary orientation of the dipole moment in the space. Based on this solution the electrodynamical aspects related to the emission and transformation of energy have been considered. In order to highlight the effect of the orientation of the dipole moment in the space we compare our results obtained for parallel orientation with those for transversal orientation. The results obtained can be used to treat qualitatively experimental and simulation data, and several phenomena of astrophysical and laboratory significance.Comment: 7 pages, 2 figures. arXiv admin note: substantial text overlap with arXiv:physics/060323

Serum alpha-fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance.

It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a cohort of patients treated with cisplatin combination chemotherapy between 1983 and 1991. A total of 669 patients were studied. Of 352 patients who had an elevated AFP at the start of treatment and for whom we had data at both day 1 and day 8, 101 (29%) had a surge. Of 317 patients for whom we had data for HCG, 80 patients (25%) had a surge. It was found that an AFP surge was a strong adverse prognostic factor for progression [hazard ratio (HR) 2.28, P=0.005]. There was no statistically significant difference in survival (HR 1.65, P=0.13). There was no prognostic significance of a HCG surge, either for progression or for survival. To investigate whether a surge was an independent prognostic factor for progression and survival, multivariate Cox regression models were fitted using the independent prognostic factors for progression and survival and the surge/decline variable. An AFP surge was retained in the final model for progression. A HCG surge was of no prognostic importance for progression or survival. We conclude that an AFP surge has an adverse prognostic significance, independent of pretreatment characteristics

Young children’s impressionable use of teleology: the influence of question wording and questioned topic on teleological explanations for natural phenomena

There is a significant body of research on children's preconceptions concerning scientific concepts and the impact this has upon their science education. One active issue concerns the extent to which young children's explanations for the existence of natural kinds rely on a teleological rationale: for example, rain is for watering the grass, or tigers’ stripes are for camouflage. It has been argued that this teleological tendency hampers children's ability to learn about causality in the natural world. This paper investigates two factors (question wording and topic) which it is argued have led to a misestimation of children's teleological tendencies within the area natural phenomena: i.e., those that are time-constrained, natural events or process such as snow, clouds or night. Sixty-six (5- to 8-years-old) children took part in a repeated-measures experiment, answering both open- and leading-questions across 10 topics of natural phenomena. The findings indicate that children's teleological reasoning may have been overestimated as open question forms significantly reduced their tendency to answer teleologically. Moreover, the concept of teleology is more nuanced than often suggested. Consequently, young children may be more able to learn about causal explanations for the existence of natural phenomena than the literature implies

Evaluation of the Antimicrobial Activity of Cationic Polymers against Mycobacteria: Toward Antitubercular Macromolecules.

Antimicrobial resistance is a global healthcare problem with a dwindling arsenal of usable drugs. Tuberculosis, caused by Mycobacterium tuberculosis, requires long-term combination therapy and multi- and totally drug resistant strains have emerged. This study reports the antibacterial activity of cationic polymers against mycobacteria, which are distinguished from other Gram-positive bacteria by their unique cell wall comprising a covalently linked mycolic acid-arabinogalactan-peptidoglycan complex (mAGP), interspersed with additional complex lipids which helps them persist in their host. The present study finds that poly(dimethylaminoethyl methacrylate) has particularly potent antimycobacterial activity and high selectivity over two Gram-negative strains. Removal of the backbone methyl group (poly(dimethylaminoethyl acrylate)) decreased antimycobacterial activity, and poly(aminoethyl methacrylate) also had no activity against mycobacteria. Hemolysis assays revealed poly(dimethylaminoethyl methacrylate) did not disrupt red blood cell membranes. Interestingly, poly(dimethylaminoethyl methacrylate) was not found to permeabilize mycobacterial membranes, as judged by dye exclusion assays, suggesting the mode of action is not simple membrane disruption, supported by electron microscopy analysis. These results demonstrate that synthetic polycations, with the correctly tuned structure are useful tools against mycobacterial infections, for which new drugs are urgently required