56 research outputs found

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    Le Lagadec, MD ORCiD: 0000-0003-0114-8552'Abnormal vertical growth' (AVG) was recognised in Australia as a dysfunction of macadamia (Macadamia spp.) in the mid-1990s. Affected trees displayed unusually erect branching, and poor flowering and yield. Since 2002, the commercial significance of AVG, its cause, and strategies to alleviate its affects, has been studied. The cause is still unknown, and AVG remains a serious threat to orchard viability. AVG affects both commercial and urban macadamia. It occurs predominantly in the warmer-drier production regions of Queensland and New South Wales. An estimated 100,000 orchard trees are affected, equating to an annual loss of $ 10.5 M. In orchards, AVG occurs as aggregations of affected trees, affected tree number can increase by 4.5% per year, and yield reduction can exceed 30%. The more upright cultivars 'HAES 344' and '741' are highly susceptible, while the more spreading cultivars 'A4', 'A16' and 'A268' show tolerance. Incidence is higher (p<0.05) in soils of high permeability and good drainage. No soil chemical anomaly has been found. Fine root dry weight of AVG trees (0-15 cm depth) was found lower (p<0.05) than non-AVG. Next generation sequencing has led to the discovery of a new Bacillus sp. and a bipartite Geminivirus, which may have a role in the disease. Trunk cinctures will increase (p<0.05) yield of moderately affected trees. Further research is needed to clarify whether a pathogen is the cause, the role of soil moisture in AVG, and develop a varietal solution

    Nouvelles données sur la séquence aurignacienne de la grotte d'Isturitz (communes d'Isturitz et de Saint-Martin-d'Arberoue. Pyrénées-Atlantiques)

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    Isturitz Cave is located in the western Pyrenees in the heart of the zone of passage and contact between the Aquitaine region and the Vasco-Cantabrian ledge. Excavations during the first half of the 20th century yielded a remarkable archaeological sequence covering the Middle Palaeolithic and the entire Upper Palaeolithic. New research conducted in the Saint-Martin chamber has revealed intensive Aurignacian occupations attributed to the archaic and early phases of this techno-complex. In this paper, we present a synthesis of the principal data that make Isturitz a key site in the study of this period.Située dans les Pyrénées occidentales, au coeur de la zone de passage et de contact entre l'Aquitaine et la corniche vasco-cantabrique, la grotte d'Isturitz a fait l'objet, dans la premiÚre moitié du XXe siÚcle, de fouilles qui ont livré un remarquable ensemble archéologique couvrant le Paléolithique moyen et la quasi-totalité du Paléolithique supérieur. De nouvelles recherches menées dans la salle de Saint-Martin ont mis en évidence d'importantes occupations aurignaciennes attribuées aux phases archaïques et anciennes de ce technocomplexe. Nous ferons dans cet article une synthÚse des principales données qui font de la grotte d'Isturitz un site clef pour l'étude de celles-ci

    Developing an institutional framework for supporting supervisors of research students: A practical guide

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    This booklet describes the outcomes of a unique interinstitutional project undertaken in Ireland between 2008 and 2012 to develop a common framework for the support of supervisors of postgraduate research students. The experiences of the seven institutions who ultimately participated in the project are summarized in the form of a series of commentaries on approaches to such training, and a description of the primary elements of the final framework itself. It is intended that this information may be of use to any institutions interested in developing their own supports for research supervisors, and ultimately will be of benefit to the supervisors themselves and, of course, their students

    Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

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    BACKGROUND: Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. METHODS: Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC) samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. RESULTS: Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9) as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. CONCLUSIONS: These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies

    Identification of Eps15 as Antigen Recognized by the Monoclonal Antibodies aa2 and ab52 of the Wuerzburg Hybridoma Library against Drosophila Brain

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    The Wuerzburg Hybridoma Library against the Drosophila brain represents a collection of around 200 monoclonal antibodies that bind to specific structures in the Drosophila brain. Here we describe the immunohistochemical staining patterns, the Western blot signals of one- and two-dimensional electrophoretic separation, and the mass spectrometric characterization of the target protein candidates recognized by the monoclonal antibodies aa2 and ab52 from the library. Analysis of a mutant of a candidate gene identified the Drosophila homolog of the Epidermal growth factor receptor Pathway Substrate clone 15 (Eps15) as the antigen for these two antibodies

    Synphilin-1 Enhances α-Synuclein Aggregation in Yeast and Contributes to Cellular Stress and Cell Death in a Sir2-Dependent Manner

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    © 2010 BĂŒttner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Parkinson’s disease is characterized by the presence of cytoplasmic inclusions, known as Lewy bodies, containing both aggregated α-synuclein and its interaction partner, synphilin-1. While synphilin-1 is known to accelerate inclusion formation by α-synuclein in mammalian cells, its effect on cytotoxicity remains elusive. Methodology/Principal Findings: We expressed wild-type synphilin-1 or its R621C mutant either alone or in combination with α-synuclein in the yeast Saccharomyces cerevisiae and monitored the intracellular localization and inclusion formation of the proteins as well as the repercussions on growth, oxidative stress and cell death. We found that wild-type and mutant synphilin-1 formed inclusions and accelerated inclusion formation by α-synuclein in yeast cells, the latter being correlated to enhanced phosphorylation of serine-129. Synphilin-1 inclusions co-localized with lipid droplets and endomembranes. Consistently, we found that wild-type and mutant synphilin-1 interacts with detergent-resistant membrane domains, known as lipid rafts. The expression of synphilin-1 did not incite a marked growth defect in exponential cultures, which is likely due to the formation of aggresomes and the retrograde transport of inclusions from the daughter cells back to the mother cells. However, when the cultures approached stationary phase and during subsequent ageing of the yeast cells, both wild-type and mutant synphilin-1 reduced survival and triggered apoptotic and necrotic cell death, albeit to a different extent. Most interestingly, synphilin-1 did not trigger cytotoxicity in ageing cells lacking the sirtuin Sir2. This indicates that the expression of synphilin-1 in wild-type cells causes the deregulation of Sir2-dependent processes, such as the maintenance of the autophagic flux in response to nutrient starvation. Conclusions/Significance: Our findings demonstrate that wild-type and mutant synphilin-1 are lipid raft interacting proteins that form inclusions and accelerate inclusion formation of α-synuclein when expressed in yeast. Synphilin-1 thereby induces cytotoxicity, an effect most pronounced for the wild-type protein and mediated via Sir2-dependent processes.This work was supported by grants from IWT-Vlaanderen (SBO NEURO-TARGET), the K.U.Leuven Research Fund (K.U.Leuven BOF-IOF) and K.U.Leuven R&D to JW, a Tournesol grant from Egide (Partenariat Hubert Curien) in France in collaboration with the Flemish Ministry of Education and the Fund of Scientific Research of Flanders (FWO) in Belgium to JW, MCG and LB, a shared PhD fellowship of the EU-Marie Curie PhD Graduate School NEURAD to JW, MCG and LB, grants of the Austrian Science Fund FWF (Austria) to FM and DR (S-9304-B05), to FM and SB (LIPOTOX), and to SB (T-414-B09; Hertha-Firnberg Fellowship) and an EMBO Installation Grant, a Marie Curie IRG, and a grant of the Fundação para a CiĂȘncia e Tecnologia (PTDC/SAU-NEU/105215/2008) to TFO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Revue d'histoire du Bas-Saint-Laurent, vol. 11 (4)

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    Éditorial: Une 15e annĂ©e qui finit en beautĂ© -- Au grĂ© du fleuve et de l'histoire -- A. propos des archive

    A rapid and direct method for the determination of active site accessibility in proteins based on ESI-MS and active site titrations

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    We have developed an electrospray ionisation mass spectrometry (ESI-MS) technique that can be applied to rapidly determine the number of intact active sites in proteins. The methodology relies on inhibiting the protein with an active-site irreversible inhibitor and then using ESI-MS to determine the extent of inhibition. We have applied this methodology to a test system: a serine protease, subtilisin Carlsberg, and monitored the extent of inhibition by phenylmethylsulfonyl fluoride (PMSF), an irreversible serine hydrolase inhibitor as a function of the changes in immobilisation and hydration conditions. Two types of enzyme preparation were investigated, lyophilised enzymes and protein-coated microcrystal

    'Abnormal vertical growth': A disorder threatening the viability of the Australian macadamia industry

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    'Abnormal vertical growth' (AVG) was recognised in Australia as a dysfunction of macadamia (Macadamia spp.) in the mid-1990s. Affected trees displayed unusually erect branching, and poor flowering and yield. Since 2002, the commercial significance of AVG, its cause, and strategies to alleviate its affects, has been studied. The cause is still unknown, and AVG remains a serious threat to orchard viability. AVG affects both commercial and urban macadamia. It occurs predominantly in the warmer-drier production regions of Queensland and New South Wales. An estimated 100,000 orchard trees are affected, equating to an annual loss of $ 10.5 M. In orchards, AVG occurs as aggregations of affected trees, affected tree number can increase by 4.5% per year, and yield reduction can exceed 30%. The more upright cultivars 'HAES 344' and '741' are highly susceptible, while the more spreading cultivars 'A4', 'A16' and 'A268' show tolerance. Incidence is higher (p<0.05) in soils of high permeability and good drainage. No soil chemical anomaly has been found. Fine root dry weight of AVG trees (0-15 cm depth) was found lower (p<0.05) than non-AVG. Next generation sequencing has led to the discovery of a new Bacillus sp. and a bipartite Geminivirus, which may have a role in the disease. Trunk cinctures will increase (p<0.05) yield of moderately affected trees. Further research is needed to clarify whether a pathogen is the cause, the role of soil moisture in AVG, and develop a varietal solution
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