A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20

Recent linkage studies and association analyses indicate the presence of at least one type 2 diabetes susceptibility gene in human chromosome region 20q12-q13.1. We have constructed a high-resolution 6.0-megabase (Mb) transcript map of this interval using two parallel, complementary strategies to construct the map. We assembled a series of bacterial artificial chromosome (BAC) contigs from 56 overlapping BAC clones, using STS/marker screening of 42 genes, 43 ESTs, 38 STSs, 22 polymorphic, and 3 BAC end sequence markers. We performed map assembly with GraphMap, a software program that uses a greedy path searching algorithm, supplemented with local heuristics. We anchored the resulting BAC contigs and oriented them within a yeast artificial chromosome (YAC) scaffold by observing the retention patterns of shared markers in a panel of 21 YAC clones. Concurrently, we assembled a sequence-based map from genomic sequence data released by the Human Genome Project, using a seed-and-walk approach. The map currently provides near-continuous coverage between SGC32867 and WI-17676 (∼ 6.0 Mb). EST database searches and genomic sequence alignments of ESTs, mRNAs, and UniGene clusters enabled the annotation of the sequence interval with experimentally confirmed and putative transcripts. We have begun to systematically evaluate candidate genes and novel ESTs within the transcript map framework. So far, however, we have found no statistically significant evidence of functional allelic variants associated with type 2 diabetes. The combination of the BAC transcript map, YAC-to-BAC scaffold, and reference Human Genome Project sequence provides a powerful integrated resource for future genomic analysis of this region

On the origin & thermal stability of Arrokoth's and Pluto's ices

International audienceWe discuss in a thermodynamic, geologically empirical way the long-term nature of the stable majority ices that could be present in Kuiper Belt Object 2014 MU69 after its 4.6 Gyr residence in the EKB as a cold classical object. Considering the stability versus sublimation into vacuum for the suite of ices commonly found on comets, Centaurs, and KBOs at the average ~40K sunlit surface temperature of MU69 over Myr to Gyr, we find only 3 common ices that are truly refractory: HCN, CH3OH, and H2O (in order of increasing stability). NH3 and H2CO ices are marginally stable and may be removed by any positive temperature excursions in the EKB, as produced every 1e8 - 1e9 yrs by nearby supernovae and passing O/B stars. To date the NH team has reported the presence of abundant CH3OH and evidence for H2O on MU69s surface (Lisse et al. 2017, Grundy et al. 2020). NH3 has been searched for, but not found. We predict that future absorption feature detections will be due to an HCN or poly-H2CO based species. Consideration of the conditions present in the EKB region during the formation era of MU69 lead us to infer that it formed "in the dark", in an optically thick mid-plane, unable to see the nascent, variable, highly luminous Young Stellar Object-TTauri Sun, and that KBOs contain HCN and CH3OH ice phases in addition to the H2O ice phases found in their Short Period comet descendants. Finally, when we apply our ice thermal stability analysis to bodies/populations related to MU69, we find that methanol ice may be ubiquitous in the outer solar system; that if Pluto is not a fully differentiated body, then it must have gained its hypervolatile ices from proto-planetary disk sources in the first few Myr of the solar systems existence; and that hypervolatile rich, highly primordial comet C/2016 R2 was placed onto an Oort Cloud orbit on a similar timescale

Coming to Terms with Quality: UNISON and the Restructuring of Local Government

The authors' argument is that current quality initiatives are managerially driven and coincide with the development of so-called ‘new right’ politics in the public sector. They criticize those those who argue that quality is simply imposed on a quiescent workforce and suggest instead that the process is mediated through workers and their representatives. They use case study evidence from a local authority to analyse trade union responses and locate this within a discussion of the ‘union renewal’ thesis

Genetic factors in the pathogenesis of CPPD crystal deposition disease

Crystal deposition is a very complex process ruled by numerous factors. A small but important proportion of cases of chondrocalcinosis are monogenic, and many of the genes involved have been identified. These genetic findings strongly point to control of the level of extracellular inorganic pyrophosphate as the primary mechanism for their association with either calcium pyrophosphate dihydrate or hydroxyapatite deposition. However, effects on extracellular inorganic pyrophosphate levels do not explain the mechanism of association in all of these monogenic diseases. Further, there are likely to be several as yet unidentified genes that are important in this common condition. This review highlights what genetic studies have demonstrated about the processes involved in these diverse but related disorders. Copyrigh