Splint ligation of RNA with T4 DNA ligase

Splint ligation of RNA, whereby specific RNA molecules are ligated together, can be carried out using T4 DNA ligase and a bridging DNA oligonucleotide complementary to the RNAs. This method takes advantage of the property of T4 DNA ligase to join RNA molecules when they are in an RNA:DNA hybrid. Splint ligation is a useful tool for the introduction of modified nucleotides into RNA molecules, insertion of a radiolabel into a specific position within an RNA and for the assembly of smaller synthetic RNAs into longer RNA molecules. Such modifications enable a wide range of experiments to be carried out with the modified RNA including structural studies, co-immunoprecipitations, and the ability to map sites of RNA:RNA and RNA:protein interactions

Hanford immobilized LAW product acceptance: Initial Tanks Focus Area testing data package

The Hanford Site's mission has been to produce nuclear materials for the US Department of Energy (DOE) and its predecessors. A large inventory of radioactive and mixed waste, largely generated during plutonium production, exists in 177 underground single- and double-shell tanks. These wastes are to be retrieved and separated into low-activity waste (LAW) and high-level waste (HLW) fractions. The total volume of LAW requiring immobilization will include the LAW separated from the tank waste, as well as new wastes generated by the retrieval, pretreatment, and immobilization processes. Per the Tri-Party Agreement (1994), both the LAW and HLW will be vitrified. It has been estimated that vitrification of the LAW waste will result in over 500,000 metric tons or 200,000 m{sup 3} of immobilized LAW (ILAW) glass. The ILAW glass is to be disposed of onsite in a near-surface burial facility. It must be demonstrated that the disposal system will adequately retain the radionuclides and prevent contamination of the surrounding environment. This report describes a study of the impacts of systematic glass-composition variation on the responses from accelerated laboratory corrosion tests of representative LAW glasses. A combination of two tests, the product consistency test and vapor-hydration test, is being used to give indictations of the relative rate at which a glass could be expected to corrode in the burial scenario

Rural training pathways: the return rate of doctors to work in the same region as their basic medical training

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Limited evidence exists about the extent to which doctors are returning to rural region(s) where they had previously trained. This study aims to investigate the rate at which medical students who have trained for 12 months or more in a rural region return to practice in that same region in their early medical career. A secondary aim is to investigate whether there is an independent or additional association with the effect of longer duration of rural exposure in a region (18-24 months) and for those completing both schooling and training in the same rural region. Methods: The outcome was rural region of work, based on postcode of work location in 2017 for graduates spanning 1-9 years post-graduation, for one large medical program in Victoria, Australia. Region of rural training, combined with region of secondary schooling and duration of rural training, was explored for its association with region of practice. A multinomial logistic regression model, accounting for other covariates, measured the strength of association with practising in the same rural region as where they had trained. Results: Overall, 357/2451 (15%) graduates were working rurally, with 90/357 (25%) working in the same rural region as where they did rural training. Similarly, 41/170 (24%) were working in the same region as where they completed schooling. Longer duration (18-24 vs 12 months) of rural training (relative risk ratio, RRR, 3.37, 1.89–5.98) and completing both schooling and training in the same rural region (RRR: 4.47, 2.14-9.36) were associated with returning to practice in the same rural region after training. Conclusions: Medical graduates practising rurally in their early career (1-9 years post-graduation) are likely to have previous connections to the region, through either their basic medical training, their secondary schooling, or both. Social accountability of medical schools and rural medical workforce outcomes could be improved by policies that enable preferential selection and training of prospective medical students from rural regions that need more doctors, and further enhanced by longer duration of within-region training.University funds only

Association analysis of chromosome 1 migraine candidate genes

Migraine with aura (MA) is a subtype of typical migraine. Migraine with aura (MA) also encompasses a rare severe subtype Familial Hemiplegic Migraine (FHM) with several known genetic loci. The type 2 FHM (FHM-2) susceptibility locus maps to chromosome 1q23 and mutations in the ATP1A2 gene at this site have recently been implicated. We have previously provided evidence of linkage of typical migraine (predominantly MA) to microsatellite markers on chromosome 1, in the 1q31 and 1q23 regions. In this study, we have undertaken a large genomic investigation involving candidate genes that lie within the chromosome 1q23 and 1q31 regions using an association analysis approach. Methods We have genotyped a large population of case-controls (243 unrelated Caucasian migraineurs versus 243 controls) examining a set of 5 single nucleotide polymorphisms (SNPs) and the Fas Ligand dinucleotide repeat marker, located within the chromosome 1q23 and 1q31 regions. Results Several genes have been studied including membrane protein (ATP 1 subtype A4 and FasL), cytoplasmic glycoprotein (CASQ 1) genes and potassium (KCN J9 and KCN J10) and calcium (CACNA1E) channel genes in 243 migraineurs (including 85% MA and 15% of migraine without aura (MO)) and 243 matched controls. After correction for multiple testing, chi-square results showed non-significant P values (P > 0.008) across all SNPs (and a CA repeat) tested in these different genes, however results with the KCN J10 marker gave interesting results (P = 0.02) that may be worth exploring further in other populations. Conclusion These results do not show a significant role for the tested candidate gene variants and also do not support the hypothesis that a common chromosome 1 defective gene influences both FHM and the more common forms of migraine