The Canada-UK Deep Submillimetre Survey - VIII. Source identifications in the 3-hour field

We present optical, near-infrared (IR) and radio observations of the 3-hour field of the Canada-UK Deep Submillimetre Survey (CUDSS). Of the 27 submillimetre sources in the field, nine have secure identifications with either a radio source or a near-IR source. We show that the percentage of sources with secure identifications in the CUDSS is consistent with that found for the bright ‘8-mJy' submillimetre survey, once allowance is made for the different submillimetre and radio flux limits. Of the 14 secure identifications in the two CUDSS fields, eight are very red objects (VROs) or extremely red objects (EROs), five have colours typical of normal galaxies and one is a radio source that has not yet been detected at optical/near-IR wavelengths. 11 of the identifications have optical/near-IR structures which are either disturbed or have some peculiarity that suggests that the host galaxy is part of an interacting system. One difference between the CUDSS results and the results from the 8-mJy survey is the large number of low-redshift objects in the CUDSS. We give several arguments why these are genuine low-redshift submillimetre sources rather than being gravitational lenses that are gravitationally amplifying a high-z submillimetre source. We construct a K-z diagram for various classes of high-redshift galaxy and show that the SCUBA galaxies are on average less luminous than classical radio galaxies, but are very similar in both their optical/IR luminosities and their colours to the host galaxies of the radio sources detected in μJy radio survey

Poverty in the Social World of the Wise

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68560/2/10.1177_030908928701203704.pd

COSMIC 2005

The Catalogue Of Somatic Mutations In Cancer (COSMIC) database and web site was developed to preserve somatic mutation data and share it with the community. Over the past 25 years, approximately 350 cancer genes have been identified, of which 311 are somatically mutated. COSMIC has been expanded and now holds data previously reported in the scientific literature for 28 known cancer genes. In addition, there is data from the systematic sequencing of 518 protein kinase genes. The total gene count in COSMIC stands at 538; 25 have a mutation frequency above 5% in one or more tumour type, no mutations were found in 333 genes and 180 are rarely mutated with frequencies <5% in any tumour set. The COSMIC web site has been expanded to give more views and summaries of the data and provide faster query routes and downloads. In addition, there is a new section describing mutations found through a screen of known cancer genes in 728 cancer cell lines including the NCI-60 set of cancer cell lines

The Canada-UK Deep Submillimetre Survey VIII: Source Identifications in the 3-hour field

We present optical, near-infrared and radio observations of the 3-hour field of the Canada-UK Deep Submillimetre Survey. Of the 27 submillimetre sources in the field, nine have secure identifications with either a radio source or a near-IR source. We show that the percentage of sources with secure identifications in the CUDSS is consistent with that found for the bright `8 mJy' submillimetre survey, once allowance is made for the different submillimetre and radio flux limits. Of the 14 secure identifications in the two CUDSS fields, eight are VROs or EROs, five have colours typical of normal galaxies, and one is a radio source which has not yet been detected at optical/near-IR wavelengths. Eleven of the identifications have optical/near-IR structures which are either disturbed or have some peculiarity which suggests that the host galaxy is part of an interacting system. One difference between the CUDSS results and the results from the 8-mJy survey is the large number of low-redshift objects in the CUDSS; we give several arguments why these are genuine low-redshift submillimetre sources rather than being gravitational lenses which are gravitationally amplifying a high-$z$ submillimetre source. We construct a $K-z$ diagram for various classes of high-redshift galaxy and show that the SCUBA galaxies are on average less luminous than classical radio galaxies, but are very similar in both their optical/IR luminosities and their colours to the host galaxies of the radio sources detected in $\mu$Jy radio surveys.Comment: accepted for publication in MNRAS, 18 pages, full-resolution versions of Figure 1 and 2 can be found at http://www.astro.cf.ac.uk/groups/cosmo/papers.htm

CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response

Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1

CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response

Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1

The origin and speciation of orchids

SummaryOrchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis.We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants.The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica.These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation

Concordant Signaling Pathways Produced by Pesticide Exposure in Mice Correspond to Pathways Identified in Human Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disease in which the etiology of 90 percent of the patients is unknown. Pesticide exposure is a major risk factor for PD, and paraquat (PQ), pyridaben (PY) and maneb (MN) are amongst the most widely used pesticides. We studied mRNA expression using transcriptome sequencing (RNA-Seq) in the ventral midbrain (VMB) and striatum (STR) of PQ, PY and paraquat+maneb (MNPQ) treated mice, followed by pathway analysis. We found concordance of signaling pathways between the three pesticide models in both the VMB and STR as well as concordance in these two brain areas. The concordant signaling pathways with relevance to PD pathogenesis were e.g. axonal guidance signaling, Wnt/β-catenin signaling, as well as pathways not previously linked to PD, e.g. basal cell carcinoma, human embryonic stem cell pluripotency and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Human PD pathways previously identified by expression analysis, concordant with VMB pathways identified in our study were axonal guidance signaling, Wnt/β-catenin signaling, IL-6 signaling, ephrin receptor signaling, TGF-β signaling, PPAR signaling and G-protein coupled receptor signaling. Human PD pathways concordant with the STR pathways in our study were Wnt/β-catenin signaling, axonal guidance signaling and G-protein coupled receptor signaling. Peroxisome proliferator activated receptor delta (Ppard) and G-Protein Coupled Receptors (GPCRs) were common genes in VMB and STR identified by network analysis. In conclusion, the pesticides PQ, PY and MNPQ elicit common signaling pathways in the VMB and STR in mice, which are concordant with known signaling pathways identified in human PD, suggesting that these pathways contribute to the pathogenesis of idiopathic PD. The analysis of these networks and pathways may therefore lead to improved understanding of disease pathogenesis, and potential novel therapeutic targets

The Pleiotropic CymR Regulator of Staphylococcus aureus Plays an Important Role in Virulence and Stress Response

We have characterized a novel pleiotropic role for CymR, the master regulator of cysteine metabolism. We show here that CymR plays an important role both in stress response and virulence of Staphylococcus aureus. Genes involved in detoxification processes, including oxidative stress response and metal ion homeostasis, were differentially expressed in a ΔcymR mutant. Deletion of cymR resulted in increased sensitivity to hydrogen peroxide-, disulfide-, tellurite- and copper-induced stresses. Estimation of metabolite pools suggests that this heightened sensitivity could be the result of profound metabolic changes in the ΔcymR mutant, with an increase in the intracellular cysteine pool and hydrogen sulfide formation. Since resistance to oxidative stress within the host organism is important for pathogen survival, we investigated the role of CymR during the infectious process. Our results indicate that the deletion of cymR promotes survival of S. aureus inside macrophages, whereas virulence of the ΔcymR mutant is highly impaired in mice. These data indicate that CymR plays a major role in virulence and adaptation of S. aureus for survival within the host

ESUR prostate MR guidelines 2012

The aim was to develop clinical guidelines for multi-parametric MRI of the prostate by a group of prostate MRI experts from the European Society of Urogenital Radiology (ESUR), based on literature evidence and consensus expert opinion. True evidence-based guidelines could not be formulated, but a compromise, reflected by “minimal” and “optimal” requirements has been made. The scope of these ESUR guidelines is to promulgate high quality MRI in acquisition and evaluation with the correct indications for prostate cancer across the whole of Europe and eventually outside Europe. The guidelines for the optimal technique and three protocols for “detection”, “staging” and “node and bone” are presented. The use of endorectal coil vs. pelvic phased array coil and 1.5 vs. 3 T is discussed. Clinical indications and a PI-RADS classification for structured reporting are presented