Provenance of the Variscan Upper Allochthon (Cabo Ortegal complex, NW Iberian Massif)

The NW Iberian Massif shows very good exposures and complete sections of the Variscan orogeny of Western Europe. Located above ophiolitic units which outline the Variscan suture, the Upper Allochthon (Upper Units) of the NW Iberian allochthonous complexes is composed of Early–Middle Cambrian magmatic arc related rocks, with siliciclastic and pelitic sedimentary series connected with basin development in this arc context. This Upper Allochthon can be followed in the same structural position along the Variscan belt, from the Iberian to the Bohemian Massifs. This study focusses on the provenance of the Cariño gneiss formation, a gneissic metasiliciclastic unit located in the uppermost structural position of the allochthonous Cabo Ortegal complex. U-Pb and Lu-Hf zircon (LA-ICPMS) and Sm-Nd whole rock analyses have been performed to document the provenance of this unit and so constrain the paleogeographic evolution of the Upper Allochthon. U-Pb geochronology of 6 samples indicates a Middle Cambrian maximum depositional age, with the following zircon age populations: Paleozoic–Neoproterozoic 36 %, Mesoproterozoic 3.6 %, Paleoproterozoic 46.8 % and Archean 13.6 %. Lu-Hf isotope analyses of these zircons typify Pan-African (Cadomian), Eburnean and Archean orogenic pulses in their respective source areas. Pan-African and Eburnean events entailed abundant input of juvenile material involving broad mixing with older crustal sources. Mesoproterozoic activity is scarce and scattered and so unlikely to represent a major crust generation pulse in the source area of the siliciclastic unit. Sm-Nd whole-rock analyses on 10 samples providean average depleted mantle model age of 1.73 Ga. This information is compatible with provenance from a source area with Archean crust that registered an important Eburnean orogenic cycle followed by a Pan-African–Cadomian event. Nd TDM ages suggest almost direct derivation from these sources. These data are interpreted as indicative of West Africa craton provenance. The siliciclastic series from which the Cariño gneisses were derived were probably deposited in a back-arc type basin where detritus were mostly sourced from the stable continental area instead of the magmatic arc. Pre-existing U-Pb and Sm-Nd data from another Upper Allochthon unit from NW Iberia (Órdenes complex) points to strong isotopic heterogeneity within this terrane, which is indicative of source area variability. This observation is interpreted to reflect either a temporal evolution of the arc or the possibility that the terrane represented by the Upper Units is composed of more than one domain of the arc-related system.Peer Reviewe

Allochthonous terranes involved in the Variscan suture from NW Iberia: a review of their origin and tectonothermal evolution [Abstract]

NW Iberia includes a rather complete section of the Variscan suture, where different terranes with continental or oceanic affinities appear with clear structural relationships. Three groups of terranes, namely upper, ophiolitic and basal units and a frontal tectonic mélange appear in Galicia, in Cabo Ortegal, Órdenes and Malpica-Tui complexes. They constitute a huge allochthonous pile thrust over the Iberian parautochthonous and autochthonous domains, which represent the section of the Gondwanan margin that escaped continental subduction during the Variscan cycle (Schistose Domain of Galicia-Trás-os-Montes and Central Iberian Zone)Departamento de Petrología y Geoquímica, Universidad Complutense de Madrid, EspañaInstituto de Geociencias, Universidad Complutense de Madrid, EspañaInstituto de Geociencias, Consejo Superior de Investigaciones Científicas, EspañaDepartamento de Geología, Universidad de Salamanca, EspañaInstitut für Geowissenschaften, Mineralogie, Johann Wolfgang Goëthe-Universität, AlemaniaUnidad de Tres Cantos, Instituto Geológico y Minero de España, EspañaCentro de Apoyo a la Investigación de Geocronología y Geoquímica Isotópica, Universidad Complutense de Madrid, Españ

Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells.

Induced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts, mouse iPSCs (miPSCs) are reported to silence transposable elements and prevent transposable element-mediated mutagenesis. Here we apply short-read or Oxford Nanopore Technologies long-read genome sequencing to 38 bulk miPSC lines reprogrammed from 10 parental cell types, and 18 single-cell miPSC clones. While single nucleotide variants and structural variants restricted to miPSCs are rare, we find 83 de novo transposable element insertions, including examples intronic to Brca1 and Dmd. LINE-1 retrotransposons are profoundly hypomethylated in miPSCs, beyond other transposable elements and the genome overall, and harbor alternative protein-coding gene promoters. We show that treatment with the LINE-1 inhibitor lamivudine does not hinder reprogramming and efficiently blocks endogenous retrotransposition, as detected by long-read genome sequencing. These experiments reveal the complete spectrum and potential significance of mutations acquired by miPSCs.Patricia Gerdes, SueMei Lim, AdamD. Ewing, Michael R. Larcombe, Dorothy Chan, Francisco J. Sanchez-Luque, Lucinda Walker, Alexander L. Carleton, Cini James, Anja S. Knaupp, Patricia E. Carreira, Christian M. Nefzger, Ryan Lister, Sandra R. Richardson, Jose M. Polo, Geoffrey J. Faulkne

Effect of neoadjuvant treatment with anastrozole on tumour histology in postmenopausal women with large operable breast cancer

Anastrozole is an orally active, non-steroidal aromatase inhibitor which appears effective as neoadjuvant treatment of breast cancer. Histological changes have been evaluated in biopsies from large, oestrogen-receptor rich, operable breast tumours in postmenopausal women following 12 weeks of neoadjuvant anastrozole treatment (1 mg (n=12) or 10 mg (n=11)). Of the 23 patients, 18 had a clinical response following treatment. Compared with pre-treatment biopsies anastrozole-treated specimens displayed decreased cellularity and/or increased fibrosis in 15 tumours; changes in gland formation, nuclear pleomorphism, or mitoses, in 12 cases; and a reduction in Mib1 score in all tumours. Marked changes in apoptotic scores were seen following treatment but the direction of effect was inconsistent. In all 17 tumours which were positive for progesterone receptors before therapy, treatment was associated with reduced staining for progesterone receptors. There was no consistent effect of treatment on oestrogen-receptor expression. It is concluded that neoadjuvant anastrozole treatment in this patient group has marked effects on tumour histopathology but these do not always correlate with clinical response

Magnetism and the absence of superconductivity in the praseodymium–silicon system doped with carbon and boron

We searched for new structural, magnetic and superconductivity phases in the Pr-Si system using high-pressure high-temperature and arc melting syntheses. Both high and low Si concentration areas of the phase diagram were explored. Although a similar approach in the La-Si system produced new stable superconducting phases, in the Pr-Si system we did not find any new superconductors. At low Si concentrations, the arc-melted samples were doped with C or B. It was found that addition of C gave rise to multiple previously unknown ferromagnetic phases. Furthermore, X-ray refinement of the undoped samples confirmed the existence of the so far elusive Pr3Si 2 phase. © 2013 Elsevier B.V

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Study of ttbar Production in ppbar Collisions Using Total Transverse Energy

We analyze a sample of W + jet events collected with the Collider Detector at Fermilab (CDF) in ppbar collisions at sqrt(s) = 1.8 TeV to study ttbar production. We employ a simple kinematical variable "H", defined as the scalar sum of the transverse energies of the lepton, neutrino and jets. For events with a W boson and four or more jets, the shape of the "H" distribution deviates by 3.8 standard deviations from that expected from known backgrounds to ttbar production. However this distribution agrees well with a linear combination of background and ttbar events, the agreement being best for a top mass of 180 GeV/c^2.Comment: Postscript file (gzip+uuencode). 5-page, two-column PRL format (RevTex). Submitted to Phys. Rev. Lett. 09 June 199

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat