11 research outputs found

    Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

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    The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & NemĂ©sio 2007; Donegan 2008, 2009; NemĂ©sio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

    Développement de nouvelles stratégies protéomiques pour l'analyse de glycoprotéines mycobactériennes

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    Je me suis intĂ©ressĂ©e au dĂ©veloppement de mĂ©thodes d'analyses en spectromĂ©trie de masse pour la recherche et la caractĂ©risation des protĂ©ines O-mannosylĂ©es de Mycobacterium tuberculosis (Mtb). Une Ă©tude prĂ©liminaire faite au sein du laboratoire suggĂ©rait le caractĂšre indispensable du phĂ©nomĂšne de glycosylation pour la virulence du bacille. Dans un premier axe, j'ai dĂ©veloppĂ© une stratĂ©gie protĂ©omique permettant la recherche de protĂ©ines glycosylĂ©es de Mtb au sein de mĂ©langes complexes grĂące Ă  un programme informatique dĂ©diĂ© dĂ©veloppĂ© au sein du laboratoire. Nous avons pu valider une liste d'une vingtaine de glycoprotĂ©ines de Mtb. Par ailleurs, afin de pouvoir caractĂ©riser de façon prĂ©cise les profils et sites de glycosylation des glycoprotĂ©ines nouvellement identifiĂ©es de Mtb, j'ai Ă©galement mis en place des mĂ©thodes d'analyse de glycoprotĂ©ines par spectromĂ©trie de masse, en travaillant avec une protĂ©ine modĂšle de Mycobacterium smegmatis, la Fascicline. DiffĂ©rentes techniques, de l'analyse de la protĂ©ine entiĂšre Ă  l'analyse des peptides m'ont permis de caractĂ©riser le profil de glycosylation de cette protĂ©ine. Enfin, dans le but de comprendre le rĂŽle de ce processus dans la virulence de Mtb, j'ai cherchĂ© Ă  identifier et caractĂ©riser les voies mĂ©taboliques affectĂ©es par l'arrĂȘt de la glycosylation et potentiellement responsables de la perte de virulence chez le mutant Rv1002c, via une Ă©tude de protĂ©omique quantitative. L'ensemble de ces travaux devrait permettre de contribuer de façon significative Ă  la comprĂ©hension du rĂŽle fonctionnel de la mannosylation des protĂ©ines dans la modulation des activitĂ©s des mannoprotĂ©ines potentiellement impliquĂ©es dans la pathogĂ©nicitĂ© du bacille de la tuberculose.I developed some mass spectrometry methods for the search and the analysis of O-mannosylated proteins of Mycobacterium tuberculosis. A preliminary study in the laboratory showed the impact of the proteins glycosylation on the virulence of the pathogen. The first axis of the project consisted in the development of an innovative " bottum-up " proteomic approach to specifically search glycoproteins of Mycobacterium tuberculosis. For that, a dedicated bioinformatics tool was developed in the lab. I used this tool on data obtained after analysis of several proteic samples. With the use of this bioinformatic program and application of some filters we optimized, we could identify with confidence more than twenty glycoproteins of the pathogen. Moreover, to fully characterize the glycosylation of the newly identified modified proteins, we also developed some mass spectrometry methods for the analysis of the whole proteins. I worked on a model protein, the Fasciclin of Mycobacterium smegmatis, we identified the glycosylation of in the lab. Finally, this work allows to start a biological research program to evaluate the possible role of each of these newly identified glycoproteins on the virulence of the pathogen. Besides, we also performed a comparative and quantitative proteomic study of the wild type versus mutant Mtb strains to identify some metabolic ways that could be affected by the silencing of the Rv1002c gene and to analyse the systemic impact of the protein-O-mannosylation deficiency on the pathogenicity of Mtb

    Potential Plasticity of the Mannoprotein Repertoire Associated to Mycobacterium tuberculosis Virulence Unveiled by Mass Spectrometry-Based Glycoproteomics

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    To date, Mycobacterium tuberculosis (Mtb) remains the world’s greatest infectious killer. The rise of multidrug-resistant strains stresses the need to identify new therapeutic targets to fight the epidemic. We previously demonstrated that bacterial protein-O-mannosylation is crucial for Mtb infectiousness, renewing the interest of the bacterial-secreted mannoproteins as potential drug-targetable virulence factors. The difficulty of inventorying the mannoprotein repertoire expressed by Mtb led us to design a stringent multi-step workflow for the reliable identification of glycosylated peptides by large-scale mass spectrometry-based proteomics. Applied to the differential analyses of glycoproteins secreted by the wild-type Mtb strain—and by its derived mutant invalidated for the protein-O-mannosylating enzyme PMTub—this approach led to the identification of not only most already known mannoproteins, but also of yet-unknown mannosylated proteins. In addition, analysis of the glycoproteome expressed by the isogenic recombinant Mtb strain overexpressing the PMTub gene revealed an unexpected mannosylation of proteins, with predicted or demonstrated functions in Mtb growth and interaction with the host cell. Since in parallel, a transient increased expression of the PMTub gene has been observed in the wild-type bacilli when infecting macrophages, our results strongly suggest that the Mtb mannoproteome may undergo adaptive regulation during infection of the host cells. Overall, our results provide deeper insights into the complexity of the repertoire of mannosylated proteins expressed by Mtb, and open the way to novel opportunities to search for still-unexploited potential therapeutic targets

    Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia

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    International audienceBackground: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional chemotherapy but overall patient survival is poor due to highly frequent relapses. As opposed to chronic myeloid leukemia, B lymphoma or multiple myeloma, AML is one of the rare malignant hemopathies the therapy of which has not significantly improved during the past 30 years despite intense research efforts. One promising approach is to determine metabolic dependencies in AML cells. Moreover, two key metabolic enzymes, isocitrate dehydrogenases (IDH1/2), are mutated in more than 15% of AML patient, reinforcing the interest in studying metabolic reprogramming, in particular in this subgroup of patients. Methods: Using a multi-omics approach combining proteomics, lipidomics, and isotopic profiling of [U-13C] glucose and [U-13C] glutamine cultures with more classical biochemical analyses, we studied the impact of the IDH1 R132H mutation in AML cells on lipid biosynthesis. Results: Global proteomic and lipidomic approaches showed a dysregulation of lipid metabolism, especially an increase of phosphatidylinositol, sphingolipids (especially few species of ceramide, sphingosine, and sphinganine), free cholesterol and monounsaturated fatty acids in IDH1 mutant cells. Isotopic profiling of fatty acids revealed that higher lipid anabolism in IDH1 mutant cells corroborated with an increase in lipogenesis fluxes. Conclusions: This integrative approach was efficient to gain insight into metabolism and dynamics of lipid species in leukemic cells. Therefore, we have determined that lipid anabolism is strongly reprogrammed in IDH1 mutant AML cells with a crucial dysregulation of fatty acid metabolism and fluxes, both being mediated by 2-HG (2-Hydroxyglutarate) production

    Dissecting the genomic complexity underlying medulloblastoma

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    Dissecting the genomic complexity underlying medulloblastoma

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    Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity(1). Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified(2,3). WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens(4). SHH tumours show hedgehog pathway activation, and have an intermediate prognosis(2). Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges(2,3,5). The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patient

    Agricultural economics and transition: What was expected, what we observed, the lessons learned Proceedings (Volume I / II)

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    Over fifteen years have elapsed since the transition from the centrally planned economic system started in the early 1990’s. During this time agricultural and rural areas of Central and Eastern Europe have undergone profound structural changes with wide variations in the degree of transformation and in the rate of success in creating a competitive market and private ownership based food and agricultural system. By becoming member of the European Union the "transition" in its traditional interpretation has been concluded in ten of the Central East European countries. The transition to market based agriculture, however, is far from completion in Southern and Eastern Europe and especially in the CIS countries. International Association of Agricultural Economists (IAAE) and European Association of Agricultural Economists (EAAE) in collaboration with the Corvinus University of Budapest and with a number of other institutions in Hungary organized an inter-conference seminar on the subject of agricultural transition in Central and Eastern Europe and Central Asia. The major objective of the seminar was to discuss and draw conclusions on the role of agricultural policy in the transition process in the light of actual progress and current situation in Central and East European countries and in formal Soviet States. In addition the contribution of agricultural economics – both from the West and from the East – as a discipline and a profession to the transition process in agriculture were discussed. A specific objective was to identify priorities and means to strengthen the agricultural economics profession in the transition countries and determine research and educational priorities for the future. The seminar was attended by 118 participants representing 26 countries from Europe, North America and Asia. The Seminar was the largest professional meeting organized by the two associations in 2007. Over 110 abstracts were submitted and evaluated by the International Program Committee. In the two day program of the meeting, 8 presentations were made during the 3 plenary sessions, 66 papers were presented in the 15 contributed paper sessions in 8 subject categories. In addition there were 15 posters discussed in the poster session and the findings of a World Bank study on distortions of agricultural incentives in the region was the subject of a pre-conference workshop. Plenary speakers included Ulrich Koester, Johan Swinnen, Jerzy Wilkin, Zvi Lerman, Eugenia Serova and JĂłzsef Popp-GĂĄbor Udovecz. At the end of the seminar David Colman, President of IAAE gave a global assessment of the status of agricultural economics discipline and profession, while Csaba CsĂĄki, former President of IAAE made summary comments on major issues discussed during the seminar. This volume includes the plenary and contributed papers presented at the seminar and submitted for publications by the authors as well as the abstracts of the poster papers discussed. The seminar was supported and sponsored by a number of organizations and persons. All of their contributions have to be greatly acknowledged. First the two international organizations IAAE and EAAE have to be mentioned, which provided overall organizational framework and logistical support. The IAAE provided in addition a generous grant to support the participation of young agricultural economists from Central and Eastern Europe on the seminar. On the Hungarian side the Corvinus University of Budapest, the Szent IstvĂĄn University of GödöllƑ, the Research Institute for Agricultural Economics, the Hungarian Agricultural Economics Association, the Hungarian Association of Agricultural Sciences and the Hungarian Ministry of Agriculture and Rural Development were the major material and organizational supporters. The International Program committee was chaired by David Colman and Csaba CsĂĄki and included Ulrich Koester, Joe Swinnen, Eugenia Serova and Jerzy Wilkin. The local Organizing committee was chaired by Csaba ForgĂĄcs and IstvĂĄn SzƱcs and included ZoltĂĄn Lakner, AndrĂĄs NĂĄbrĂĄdi, JĂłzsef Popp, JĂłzsef TĂłth, GĂĄbor Udovecz, LĂĄszlĂł Vajda, LĂĄszlĂł VillĂĄnyi, Krisztina Fodor, Attila JĂĄmbor and TamĂĄs Mizik. Finally IAMO, Halle facilitated the publication of this proceedings
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