Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways

Rab family guanosine triphosphatases (GTPases) together with their regulators define specific pathways of membrane traffic within eukaryotic cells. In this study, we have investigated which Rab GTPase-activating proteins (GAPs) can interfere with the trafficking of Shiga toxin from the cell surface to the Golgi apparatus and studied transport of the epidermal growth factor (EGF) from the cell surface to endosomes. This screen identifies 6 (EVI5, RN-tre/USP6NL, TBC1D10A–C, and TBC1D17) of 39 predicted human Rab GAPs as specific regulators of Shiga toxin but not EGF uptake. We show that Rab43 is the target of RN-tre and is required for Shiga toxin uptake. In contrast, RabGAP-5, a Rab5 GAP, was unique among the GAPs tested and reduced the uptake of EGF but not Shiga toxin. These results suggest that Shiga toxin trafficking to the Golgi is a multistep process controlled by several Rab GAPs and their target Rabs and that this process is discrete from ligand-induced EGF receptor trafficking

The DRIFT Project: Searching for WIMPS with a Directional Detector

A low pressure time projection chamber for the detection of WIMPs is discussed. Discrimination against Compton electron background in such a device should be very good, and directional information about the recoil atoms would be obtainable. If a full 3-D reconstruction of the recoil tracks can be achieved, Monte Carlo studies indicate that a WIMP signal could be identified with high confidence from as few as 30 detected WIMP-nucleus scattering events.Comment: 5 pages, 3 figures. Presented at Dark 98, Heidelberg, July 1998, and to appear in conference proceeding

GrameneMart: the BioMart data portal for the Gramene project

Gramene is a well-established resource for plant comparative genome analysis. Data are generated through automated and curated analyses and made available through web interfaces such as GrameneMart. The Gramene project was an early adopter of the BioMart software, which remains an integral and well-used component of the Gramene website. BioMart accessible data sets include plant gene annotations, plant variation catalogues, genetic markers, physical mapping entities, public DNA/mRNA sequences of various types and curated quantitative trait loci for various species. Database URL: http://www.gramene.org/biomart/martview

Stick or twist? Career decision-making during contractual uncertainty for NHS junior doctors

OBJECTIVES: To examine the extent, and nature, of impact on junior doctors' career decisions, of a proposed new contract and the uncertainty surrounding it. DESIGN: Mixed methods. Online survey exploring: doctors' future training intentions; their preferred specialty training (ST) programmes; whether they intended to proceed immediately to ST; and other plans. Linked qualitative interviews to explore more fully how and why decisions were affected. SETTING: Doctors (F2s) in second year of Foundation School (FS) Programmes in England. PARTICIPANTS: Invitations sent by FSs. Open to all F2s November 2015-February 2016. All FSs represented. Survey completed by 816 F2s. Sample characteristics broadly similar to national F2 cohort. MAIN OUTCOME MEASURES: Proportions of doctors intending to proceed to ST posts in the UK, to defer or to exit UK medicine. Proportion of doctors indicating changes in training and career plans as a result of the contract and/or resulting uncertainty. Distribution of changes across training programmes. Explanations of these intentions from interviews and free text comments. RESULTS: Among the responding junior doctors, 20% indicated that issues related to the contract had prompted them to switch specialty and a further 20% had become uncertain about switching specialty. Switching specialty choice was more prevalent among those now choosing a community-based, rather than hospital-based specialty. 30% selecting general practice had switched choice because of the new contract. Interview data suggests that doctors felt they had become less valued or appreciated in the National Health Service and in society more broadly. CONCLUSIONS: Doctors reported that contract-related issues have affected their career plans. The most notable effect is a move away from acute to community-based specialities, with the former perceived as more negatively affected by the proposed changes. It is concerning that young doctors feel undervalued, and this requires further investigation

What's in a name; Genetic structure in Solanum section Petota studied using population-genetic tools

Background - The taxonomy and systematic relationships among species of Solanum section Petota are complicated and the section seems overclassified. Many of the presumed (sub)species from South America are very similar and they are able to exchange genetic material. We applied a population genetic approach to evaluate support for subgroups within this material, using AFLP data. Our approach is based on the following assumptions: (i) accessions that may exchange genetic material can be analyzed as if they are part of one gene pool, and (ii) genetic differentiation among species is expected to be higher than within species. Results - A dataset of 566 South-American accessions (encompassing 89 species and subspecies) was analyzed in two steps. First, with the program STRUCTURE 2.2 in an 'unsupervised' procedure, individual accessions were assigned to inferred clusters based on genetic similarity. The results showed that the South American members of section Petota could be arranged in 16 clusters of various size and composition. Next, the accessions within the clusters were grouped by maximizing the partitioning of genetic diversity among subgroups (i.e., maximizing Fst values) for all available individuals of the accessions (2767 genotypes). This two-step approach produced an optimal partitioning into 44 groups. Some of the species clustered as genetically distinct groups, either on their own, or combined with one or more other species. However, accessions of other species were distributed over more than one cluster, and did not form genetically distinct units. Conclusions - We could not find any support for 43 species (almost half of our dataset). For 28 species some level of support could be found varying from good to weak. For 18 species no conclusions could be drawn as the number of accessions included in our dataset was too low. These molecular data should be combined with data from morphological surveys, with geographical distribution data, and with information from crossing experiments to identify natural units at the species level. However, the data do indicate which taxa or combinations of taxa are clearly supported by a distinct set of molecular marker data, leaving other taxa unsupported. Therefore, the approach taken provides a general method to evaluate the taxonomic system in any species complex for which molecular data are available

First results from dark matter search experiment with LiF bolometer at Kamioka Underground Laboratory

Tokyo group has performed first underground dark matter search experiment in 2001 through 2002 at Kamioka Observatory(2700m.w.e). The detector is eight LiF bolometers with total mass 168g aiming for the direct detection of WIMPs via spin-dependent interaction. With a total exposure of 4.1 kg days, we derived the limits in the a_p-a_n (WIMP-nucleon couplings) plane and excluded a large part of the parameter space allowed by the UKDMC experiment.Comment: 15 pages, 5 figure