Optimized isolation of 7,7′-biphyscion starting from Cortinarius rubrophyllus, a chemically unexplored fungal species rich in photosensitizers

Mushrooms such as the dermocyboid Cortinarius rubrophyllus are characterized by strikingly colorful fruiting bodies. The molecular dyes responsible for such colors recently experienced a comeback as photoactive compounds with remarkable photophysical and photobiological properties. One of them-7,7'-biphyscion-is a dimeric anthraquinone that showed promising anticancer effects in the low nanomolar range under blue-light irradiation. Compared to acidic anthraquinones, 7,7'-biphyscion was more efficiently taken up by cells and induced apoptosis after photoactivation. However, seasonal collection of mushrooms producing this compound, low extraction yields, and tricky fungal identification hamper further developments to the clinics. To bypass these limitations, we demonstrate here an alternative approach utilizing a precursor of 7,7'-biphyscion, i.e., the pre-anthraquinone flavomannin-6,6'-dimethyl ether, which is abundant in many species of the subgenus Dermocybe. Controlled oxidation of the crude extract significantly increased the yield of 7,7'-biphyscion by 100%, which eased the isolation process. We also present the mycochemical and photobiological characterization of the yet chemically undescribed species, i.e. C. rubrophyllus. In total, eight pigments (1-8) were isolated, including two new glycosylated anthraquinones (1 and 2). Light-dependent generation of singlet oxygen was detected for the first time for emodin-1-O-beta-D-glucopyranoside (3) [photophysical measurement: Phi(Delta) =0.11 (CD3OD)]. Furthermore, emodin (7) was characterized as promising compound in the photocytotoxicity assay with EC50-values in the low micromolar range under irradiation against cells of the cancer cell lines AGS, A549, and T24.Metals in Catalysis, Biomimetics & Inorganic Material

The STAR Silicon Strip Detector (SSD)

The STAR Silicon Strip Detector (SSD) completes the three layers of the Silicon Vertex Tracker (SVT) to make an inner tracking system located inside the Time Projection Chamber (TPC). This additional fourth layer provides two dimensional hit position and energy loss measurements for charged particles, improving the extrapolation of TPC tracks through SVT hits. To match the high multiplicity of central Au+Au collisions at RHIC the double sided silicon strip technology was chosen which makes the SSD a half million channels detector. Dedicated electronics have been designed for both readout and control. Also a novel technique of bonding, the Tape Automated Bonding (TAB), was used to fullfill the large number of bounds to be done. All aspects of the SSD are shortly described here and test performances of produced detection modules as well as simulated results on hit reconstruction are given.Comment: 11 pages, 8 figures, 1 tabl

Soil nutrients and beta diversity in the Bornean Dipterocarpaceae: evidence for niche partitioning by tropical rain forest trees

1   The relative importance of niche- and dispersal-mediated processes in structuring diverse tropical plant communities remains poorly understood. Here, we link mesoscale beta diversity to soil variation throughout a lowland Bornean watershed underlain by alluvium, sedimentary and granite parent materials ( c . 340 ha, 8–200 m a.s.l.). We test the hypothesis that species turnover across the habitat gradient reflects interspecific partitioning of soil resources. 2   Floristic inventories (≥ 1 cm d.b.h.) of the Dipterocarpaceae, the dominant Bornean canopy tree family, were combined with extensive soil analyses in 30 (0.16 ha) plots. Six samples per plot were analysed for total C, N, P, K, Ca and Mg, exchangeable K, Ca and Mg, extractable P, texture, and pH. 3   Extractable P, exchangeable K, and total C, N and P varied significantly among substrates and were highest on alluvium. Thirty-one dipterocarp species ( n  = 2634 individuals, five genera) were recorded. Dipterocarp density was similar across substrates, but richness and diversity were highest on nutrient-poor granite and lowest on nutrient-rich alluvium. 4   Eighteen of 22 species were positively or negatively associated with parent material. In 8 of 16 abundant species, tree distribution (≥ 10 cm d.b.h.) was more strongly non-random than juveniles (1–10 cm d.b.h.), suggesting higher juvenile mortality in unsuitable habitats. The dominant species Dipterocarpus sublamellatus (> 50% of stems) was indifferent to substrate, but nine of 11 ‘subdominant’ species (> 8 individuals ha −1 ) were substrate specialists. 5   Eighteen of 22 species were significantly associated with soil nutrients, especially P, Mg and Ca. Floristic variation was significantly correlated with edaphic and geographical distance for all stems ≥ 1 cm d.b.h. in Mantel analyses. However, juvenile variation (1–10 cm d.b.h.) was more strongly related to geographical distance than edaphic factors, while the converse held for established trees (≥ 10 cm d.b.h.), suggesting increased importance of niche processes with size class. 6   Pervasive dipterocarp associations with soil factors suggest that niche partitioning structures dipterocarp tree communities. Yet, much floristic variation unrelated to soil was correlated with geographical distance between plots, suggesting that dispersal and niche processes jointly determine mesoscale beta diversity in the Bornean Dipterocarpaceae. Journal of Ecology (2005) doi: 10.1111/j.1365-2745.2005.01077.xPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72822/1/j.1365-2745.2005.01077.x.pd

Neutrino masses beyond the tree level

Models for Majorana neutrino masses can be classified according to the level in perturbation theory at which the effective dimension five operator $LLHH$ is realized. The possibilities range from the tree-level up to the three-loop level realizations. We discuss some general aspects of this approach and speculate about a model independent classification of the possible cases. Among all the realizations, those in which the effective operator is induced by radiative corrections open the possibility for lepton number violation near -or at- the electroweak scale. We discuss some phenomenological aspects of two generic radiative realizations: the Babu-Zee model and supersymmetric models with bilinear R-parity violation.Comment: 7 pages, 3 figures. Contribution to the workshop "30 years of strong interactions", Spa, Belgium, 6-8 April 201

Obinutuzumab versus Rituximab in young patients with advanced DLBCL, a PET-guided and randomized phase 3 study by LYSA.

Rituximab plus polychemotherapy is standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED trial compares obinutuzumab to rituximab. GAINED (NCT01659099) is an open-label, randomized phase 3 trial. Transplant-eligible patients (18-60yrs) with untreated aged-adjusted international prognostic index (aaIPI) ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab. Patients were stratified by aaIPI (1; 2-3) and chemotherapy regimen (ACVBP; CHOP). Consolidation treatment was determined according to response assessed by centrally reviewed interim semi-quantitative PET. Responders after cycle 2 and 4 (PET2-/PET4-) received planned immuno-chemotherapy consolidation. Responders only after cycle 4 (PET2+/4-) received highdose methotrexate plus transplantation. The primary objective was an 8% improvement (HR=0.73; 80% power; alpha risk 2.5%; one-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. Events included death, progression, PET 2 or 4 positivity, modification of planned treatment. From September 20, 2012, 670 patients were enrolled (obinutuzumab n=336; rituximab n=334). 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP and 324 (48.4%) received ACVBP. Median follow-up was 38.7 months. The 2-year EFS were similar in obinutuzumab and rituximab groups (59.8% vs 56.6%; p=0.123; HR=0.88). The 2-year PFS in the whole cohort was 83.1% (95%CI 80–85.8). PET2-/4- and PET2+/4- had similar 2-year PFS and OS (89.9% vs 83.9%) and 94.8% vs 92.8%). The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in untreated aaIPI≥1 DLBCL transplant-eligible patients

Search for heavy lepton partners of neutrinos in proton-proton collisions in the context of the type III seesaw mechanism

This is the Pre-print version of the Article. The official publishe version can be accessed from the link below - Copyright @ 2012 ElsevierA search is presented in proton–proton collisions at sqrt(s) = 7TeV for fermionic triplet states expected in type III seesaw models. The search is performed using final states with three isolated charged leptons and an imbalance in transverse momentum. The data, collected with the CMS detector at the LHC, correspond to an integrated luminosity of 4.9 fb−1. No excess of events is observed above the background predicted by the standard model, and the results are interpreted in terms of limits on production cross sections and masses of the heavy partners of the neutrinos in type III seesaw models. Depending on the considered scenarios, lower limits are obtained on the mass of the heavy partner of the neutrino that range from 180 to 210 GeV. These are the first limits on the production of type III seesaw fermionic triplet states reported by an experiment at the LHC.This study is spported by the BMWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MEYS (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); MoER, SF0690030s09 and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); MSI (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MON, RosAtom, RAS and RFBR (Russia); MSTD (Serbia); SEIDI and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); ThEP, IPST and NECTEC (Thailand); TUBITAK and TAEK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie programme and the European Research Council (European Union); the Leventis Foundation; the A. P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation a la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the Ministry of Education, Youth and Sports (MEYS) of Czech Republic; the Council of Science and Industrial Research, India; the Compagnia di San Paolo (Torino); and the HOMING PLUS programme of Foundation for Polish Science, cofinanced from European Union, Regional Development Fund

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

ÉTUDE PHYTOGÉOGRAPHIQUE DE LA HAUTE-VALLÉE DE CARENÇA (PYRÉNÉES-ORIENTALES)DEUXIÈME INVENTAIRE FLORISTIQUE

International audienc