Resurrection and emendation of the Hypoxylaceae, recognised from a multigene phylogeny of the Xylariales

A multigene phylogeny was constructed, including a significant number of representative species of the main lineages in the Xylariaceae and four DNA loci the internal transcribed spacer region (ITS), the large subunit (LSU) of the nuclear rDNA, the second largest subunit of the RNA polymerase II (RPB2), and beta-tubulin (TUB2). Specimens were selected based on more than a decade of intensive morphological and chemotaxonomic work, and cautious taxon sampling was performed to cover the major lineages of the Xylariaceae; however, with emphasis on hypoxyloid species. The comprehensive phylogenetic analysis revealed a clear-cut segregation of the Xylariaceae into several major clades, which was well in accordance with previously established morphological and chemotaxonomic concepts. One of these clades contained Annulohypoxylon, Hypoxylon, Daldinia, and other related genera that have stromatal pigments and a nodulisporium-like anamorph. They are accommodated in the family Hypoxylaceae, which is resurrected and emended. Representatives of genera with a nodulisporium-like anamorph and bipartite stromata, lacking stromatal pigments (i.e. Biscogniauxia, Camillea, and Obolarina) appeared in a clade basal to the xylarioid taxa. As they clustered with Graphostroma platystomum, they are accommodated in the Graphostromataceae. The new genus Jackrogersella with J. multiformis as type species is segregated from Annulohypoxylon. The genus Pyrenopolyporus is resurrected for Hypoxylon polyporus and allied species. The genus Daldinia and its allies Entonaema, Rhopalostroma, Ruwenzoria, and Thamnomyces appeared in two separate subclades, which may warrant further splitting of Daldinia in the future, and even Hypoxylon was divided in several clades. However, more species of these genera need to be studied before a conclusive taxonomic rearrangement can be envisaged. Epitypes were designated for several important species in which living cultures and molecular data are available, in order to stabilise the taxonomy of the Xylariales.Fil: Wendt, Lucile. Helmholtz-Zentrum für Infektionsforschung GmbH. Department of Microbial Drugs; Alemania. German Centre for Infection Research; AlemaniaFil: Sir, Esteban Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Unidad Ejecutora Lillo. Fundación Miguel Lillo. Unidad Ejecutora Lillo; ArgentinaFil: Kuhnert, Eric. Helmholtz-Zentrum für Infektionsforschung GmbH. Department of Microbial Drugs; Alemania. German Centre for Infection Research; AlemaniaFil: Heitkämper, Simone. Helmholtz-Zentrum für Infektionsforschung GmbH. Department of Microbial Drugs; Alemania. German Centre for Infection Research; AlemaniaFil: Lambert, Christopher. Helmholtz-Zentrum für Infektionsforschung GmbH. Department of Microbial Drugs; Alemania. German Centre for Infection Research; AlemaniaFil: Hladki, Adriana I.. Fundación Miguel Lillo. Dirección de Botánica. Instituto de Micologia; ArgentinaFil: Romero, Andrea Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Micología y Botánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Micología y Botánica; ArgentinaFil: Luangsa-Ard, Janet Jennifer. National Center for Genetic Engineering and Biotechnology; TailandiaFil: Srikitikulchai, Prasert. National Center for Genetic Engineering and Biotechnology; TailandiaFil: Peršoh, Derek. Ruhr-Universität Bochum; AlemaniaFil: Stadler, Marc. Helmholtz-Zentrum für Infektionsforschung GmbH. Department of Microbial Drugs; Alemania. German Centre for Infection Research; Alemani

Does adherence to inhaled corticosteroids predict asthma-related outcomes over time? A cohort study

Funding: The research leading to these results has received funding from the European Community 7th Framework (FP7/2007-2013) under grant agreement n°282593, and H2020 programme (MSCA-IF) under GA n°706028 for AD during manuscript preparation.Peer reviewedPostprin

Immortalized myogenic cells from congenital muscular dystrophy type1A patients recapitulate aberrant caspase activation in pathogenesis: a new tool for MDC1A research

BACKGROUND: Congenital muscular dystrophy Type 1A (MDC1A) is a severe, recessive disease of childhood onset that is caused by mutations in the LAMA2 gene encoding laminin-alpha2. Studies with both mouse models and primary cultures of human MDC1A myogenic cells suggest that aberrant activation of cell death is a significant contributor to pathogenesis in laminin-alpha2-deficiency. METHODS: To overcome the limited population doublings of primary cultures, we generated immortalized, clonal lines of human MDC1A myogenic cells via overexpression of both CDK4 and the telomerase catalytic component (human telomerase reverse transcriptase (hTERT)). RESULTS: The immortalized MDC1A myogenic cells proliferated indefinitely when cultured at low density in high serum growth medium, but retained the capacity to form multinucleate myotubes and express muscle-specific proteins when switched to low serum medium. When cultured in the absence of laminin, myotubes formed from immortalized MDC1A myoblasts, but not those formed from immortalized healthy or disease control human myoblasts, showed significantly increased activation of caspase-3. This pattern of aberrant caspase-3 activation in the immortalized cultures was similar to that found previously in primary MDC1A cultures and laminin-alpha2-deficient mice. CONCLUSIONS: Immortalized MDC1A myogenic cells provide a new resource for studies of pathogenetic mechanisms and for screening possible therapeutic approaches in laminin-alpha2-deficiency

Kyleo® - Ein neues Breitbandherbizid für den Einsatz auf der Stoppel

Kyleo® ist eine Coformulierung auf der Basis von 160 g/l 2,4-D (als Säure) und 240 g/l Glyphosat (MIPA Salz), die sich durch eine besonders schnelle und tiefgreifende Wirkung gegen perennierende Unkräuter, Ausfallraps und Ausfallgetreide auszeichnet. Mit 2,4-D als synthetischem Auxin und Glyphosat als EPSP Synthase-Hemmer werden zwei komplementäre Wirkstoffe aus unterschiedlichen Gruppen von Wirkungsmechanismen kombiniert. Die innovative Fertigformulierung mit 200 g/l Cocoalcylamin (FHS) ermöglicht trotz extrem unterschiedlicher pH-Ansprüche der Einzelwirkstoffe eine Kombination ohne Wirkungsverlust im Gegensatz zur Tankmischung.Generell zeigt Kyleo eine im Vergleich zu reinen Glyphosat-Formulierungen stark erhöhte Wirkungsgeschwindigkeit. Die Wirkung auf dikotyle Unkräuter in größeren Entwicklungsstadien wird durch die Kombination der beiden Wirkstoffe verbessert. Ausfallraps im 8-10 Blattstadium wird bereits mit 3 l/ha sicher erfasst, Ausfallgetreide ebenso. Auf Ausfallerbsen und -bohnen kann mit Hilfe der Coformulierung eine erheblich bessere Wirkung als mit den Soloprodukten und eine synergistische Wirkung gegenüber der Tankmischung erreicht werden. Auf Ackerkratzdistel (Cirsium arvense) wurde mit 3 l/ha eine 95 %ige Wirkung erzielt. Gegen den Ackerschachtelhalm (Equisetum arvense) werden vier Wochen nach der Anwendung Wirkungsgrade von 82 % mit 3 l/ha und 92 % mit 5 l/ha erreicht. Die Ackerwinde (Convolvulus arvense) wird mit 3 l/ha zu 88 %, mit 5 l/ha zu 100 % erfasst. Gegen die Quecke (Agropyron repens) wird mit 5 l/ha Kyleo ein Wirkungsgrad von 96 % erreicht.Durch sein breites Wirkungsspektrum und insbesondere die gute Wirkung gegen perennierende Arten, eignet sich Kyleo sehr gut für den Einsatz in Anbausystemen mit Minimalbodenbearbeitung, aber auch auf Gleisen, im Obstbau oder zur Grünlanderneuerung.Stichwörter: Ausfallgetreide, Ausfallraps, Breitbandherbizid, 2,4-D, Glyphosat, Kyleo, perennierende Unkräuter, Stoppel, WirkungsgeschwindigkeitKyleo® - A new broad spectrum herbicide for use on stubblesKyleo® is a coformulation of 160 g/l 2,4-D (as acid) and 240 g/l glyphosate (as MIPA salt), with rapid action and excellent efficacy against volunteer oilseed rape, cereals and perennial weeds. Two complementary active ingredients with different MOA are combined in an innovative coformulation using 200 g/l cocoalcylamin (adjuvant) to handle the extremely different ph requirements of the actives, avoiding a loss of efficacy that often appears using the tankmix of both.Volunteer oilseed rape at 8-10 leaf stage is controlled already with 3 l/ha, volunteer cereals as well. The efficacy against volunteer beans and peas is improved significantly versus the use of the actives and a synergistic effect can be observed compared to the tankmix of both. At 3 l/ha respectively 5 l/ha the control levels against Equisetum arvense reached 82 % and 95 %, against Convolvulus arvense 88 % respectively 100 % and against Agropyron repens 96 % with 5 l/ha.With its broad spectrum and the good efficacy against perennial weeds, Kyleo is an excellent option for for minimum tillage systems as well as for the use on railways, in orchards and for grassland renewal. Keywords: Broad spectrum, 2,4-D, glyphosate, herbicide, Kyleo, perennial weeds, rapid action, stubble, volunteer crop

The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance).

BACKGROUND: Preliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel. METHODS: In CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm. RESULTS: Baseline characteristics between patients who did (N=277) and did not (N=728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P=.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P=.342), the proportion achieving a decline ≥ 50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P=.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P=.366). CONCLUSIONS: As measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC

The common ancestral core of vertebrate and fungal telomerase RNAs

Telomerase is a ribonucleoprotein with an intrinsic telomerase RNA (TER) component. Within yeasts, TER is remarkably large and presents little similarity in secondary structure to vertebrate or ciliate TERs. To better understand the evolution of fungal telomerase, we identified 74 TERs from Pezizomycotina and Taphrinomycotina subphyla, sister clades to budding yeasts. We initially identified TER from Neurospora crassa using a novel deep-sequencing-based approach, and homologous TER sequences from available fungal genome databases by computational searches. Remarkably, TERs from these non-yeast fungi have many attributes in common with vertebrate TERs. Comparative phylogenetic analysis of highly conserved regions within Pezizomycotina TERs revealed two core domains nearly identical in secondary structure to the pseudoknot and CR4/5 within vertebrate TERs. We then analyzed N. crassa and Schizosaccharomyces pombe telomerase reconstituted in vitro, and showed that the two RNA core domains in both systems can reconstitute activity in trans as two separate RNA fragments. Furthermore, the primer-extension pulse-chase analysis affirmed that the reconstituted N. crassa telomerase synthesizes TTAGGG repeats with high processivity, a common attribute of vertebrate telomerase. Overall, this study reveals the common ancestral cores of vertebrate and fungal TERs, and provides insights into the molecular evolution of fungal TER structure and function

Performance of Landsat-8 and Sentinel-2 Surface Reflectance Products for River Remote Sensing Retrievals of Chlorophyll-A and Turbidity

Rivers and other freshwater systems play a crucial role in ecosystems, industry, transportation and agriculture. Despite the more than 40 years of inland water observations made possible by optical remote sensing, a standardized reflectance product for inland waters is yet forthcoming. The aim of this work is to compare the standard USGS land surface reflectance product to two Landsat-8 and Sentinel-2 aquatic remote sensing reflectance products over the Amazon, Columbia and Mississippi rivers. Landsat-8 reflectance products from all three routines are then evaluated for their comparative performance in retrieving chlorophyll-a and turbidity in reference to shipborne, underway in situ validation measurements. The land surface product shows the best agreement (4 percent Mean Absolute Percent Difference) with field measurements of radiometry collected on the Amazon River and generates 36 percent higher reflectance values in the visible bands compared to aquatic methods (ACOLITE (Atmospheric Correction for OLI (Operational Land Imager) 'lite') and SeaDAS (Sea-viewing Wide Field-of-View Sensor (SeaWiFS) Data Analysis System)) with larger differences between land and aquatic products observed in Sentinel-2 (0.01 per steraradian) compared to Landsat-8 (0.001 per steraradian). Choice of atmospheric correction routine can bias Landsat-8 retrievals of chlorophyll-a and turbidity by as much as 59 percent and 35 percent respectively. Using a more restrictive time window for matching in situ and satellite imagery can reduce differences by 531 percent depending on correction technique. This work highlights the challenges of satellite retrievals over rivers and underscores the need for future optical and biogeochemical research aimed at improving our understanding of the absorbing and scattering properties of river water and their relationships to remote sensing reflectance

Lactobacillus johnsonii N6.2 Mitigates the Development of Type 1 Diabetes in BB-DP Rats

BACKGROUND: The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. METHODOLOGY/PRINCIPAL: Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. CONCLUSIONS: It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data suggest that the gut and the gut microbiota are potential agents of influence in type 1 diabetes development. These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder