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951.
Nathalie Bleyzac Philippe Barou Gilles Aulagner 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2000,742(2):3255
A reversed-phase liquid chromatographic method with ultraviolet detection has been developed to determine busulfan concentrations in plasma of children undergoing bone marrow transplantation. Plasma samples (200 μl) containing busulfan and 1,6-bis(methanesulfonyloxy)hexane as an internal standard were prepared by a simple derivatization method with diethyldithiocarbamate followed by extraction with ethyl acetate and solid-phase purification on C8 columns conditioned with methanol and water and eluted with acetonitrile (recovery 99%). Chromatography was accomplished using a Hypersil octadecylsilyl column (10 cm×4.6 mm I.D.) and a mobile phase of acetonitrile, tetrahydrofuran and distilled water (65:5:30, v/v). The limit of detection was 25 ng/ml (signal-to-noise ratio of 5). Calibration curves were linear up to 25 000 ng/ml. Intra-day and inter-day coefficients of variation of the assay were ≤5%. This method was used to analyse busulfan plasma concentrations after oral administration within the framework of therapeutic drug monitoring and pharmacokinetic studies in children. 相似文献
952.
Giovanni Sgubin Didier Swingedouw Juliette Mignot Gregory Alan Gambetta Benjamin Bois Harilaos Loukos Thomas Noël Philippe Pieri Iñaki García de Cortázar-Atauri Nathalie Ollat Cornelis van Leeuwen 《Global Change Biology》2023,29(3):808-826
Evaluating the potential climatic suitability for premium wine production is crucial for adaptation planning in Europe. While new wine regions may emerge out of the traditional boundaries, most of the present-day renowned winemaking regions may be threatened by climate change. Here, we analyse the future evolution of the geography of wine production over Europe, through the definition of a novel climatic suitability indicator, which is calculated over the projected grapevine phenological phases to account for their possible contractions under global warming. Our approach consists in coupling six different de-biased downscaled climate projections under two different scenarios of global warming with four phenological models for different grapevine varieties. The resulting suitability indicator is based on fuzzy logic and is calculated over three main components measuring (i) the timing of the fruit physiological maturity, (ii) the risk of water stress and (iii) the risk of pests and diseases. The results demonstrate that the level of global warming largely determines the distribution of future wine regions. For a global temperature increase limited to 2°C above the pre-industrial level, the suitable areas over the traditional regions are reduced by about 4%/°C rise, while for higher levels of global warming, the rate of this loss increases up to 17%/°C. This is compensated by a gradual emergence of new wine regions out of the traditional boundaries. Moreover, we show that reallocating better-suited grapevine varieties to warmer conditions may be a viable adaptation measure to cope with the projected suitability loss over the traditional regions. However, the effectiveness of this strategy appears to decrease as the level of global warming increases. Overall, these findings suggest the existence of a safe limit below 2°C of global warming for the European winemaking sector, while adaptation might become far more challenging beyond this threshold. 相似文献
953.
Transposable elements (TEs) are present in roughly all genomes. These mobile DNA sequences are able to invade genomes and their impact on genome evolution is substantial. The mobility of TEs can induce the appearance of deleterious mutations, gene disruption and chromosome rearrangements, but transposition activity also has positive aspects and the mutational activities of TEs contribute to the genetic diversity of organisms. This short review aims to give a brief overview of the impact TEs may have on animal and plant genome structure and expression, and the relationship between TEs and the stress response of organisms, including insecticide resistance. 相似文献
954.
Khaoula Rochdi Cerino Mathieu Da Silva Nathalie Delague Valerie Nahili Halima Kriouile Yamna Gorokhova Svetlana Bartoli Marc Saïle Rachid Barakat Abdelhamid Krahn Martin 《Molecular biology reports》2021,48(10):6999-7006
Molecular Biology Reports - Congenital myasthenic syndromes (CMS) are associated with defects in the structure and the function of neuromuscular junctions. These rare disorders can result from... 相似文献
955.
Maurizio Scarpa Zsuzsanna Almássy Michael Beck Olaf Bodamer Iain A Bruce Linda De Meirleir Nathalie Guffon Encarna Guillén-Navarro Pauline Hensman Simon Jones Wolfgang Kamin Christoph Kampmann Christina Lampe Christine A Lavery Elisa Leão Teles Bianca Link Allan M Lund Gunilla Malm Susanne Pitz Michael Rothera Catherine Stewart Anna Tylki-Szymańska Ans van der Ploeg Robert Walker Jiri Zeman James E Wraith 《Orphanet journal of rare diseases》2011,6(1):1-18
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Mucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2-sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs and symptoms, and disease progression are heterogeneous, and patients may present with many different manifestations to a wide range of specialists. Expertise in diagnosing and managing MPS II varies widely between countries, and substantial delays between disease onset and diagnosis can occur. In recent years, disease-specific treatments such as enzyme replacement therapy and stem cell transplantation have helped to address the underlying enzyme deficiency in patients with MPS II. However, the multisystem nature of this disorder and the irreversibility of some manifestations mean that most patients require substantial medical support from many different specialists, even if they are receiving treatment. This article presents an overview of how to recognise, diagnose, and care for patients with MPS II. Particular focus is given to the multidisciplinary nature of patient management, which requires input from paediatricians, specialist nurses, otorhinolaryngologists, orthopaedic surgeons, ophthalmologists, cardiologists, pneumologists, anaesthesiologists, neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, social workers, homecare companies and patient societies.Take-home message
Expertise in recognising and treating patients with MPS II varies widely between countries. This article presents pan-European recommendations for the diagnosis and management of this life-limiting disease. 相似文献956.
Souha Berriri Ana Victoria Garcia Nicolas Frei dit Frey Wilfried Rozhon Stéphanie Pateyron Nathalie Leonhardt Jean-Luc Montillet Jeffrey Leung Heribert Hirt Jean Colcombet 《The Plant cell》2012,24(10):4281-4293
Plant mitogen-activated protein kinases (MAPKs) are involved in important processes, including stress signaling and development. In a functional yeast screen, we identified mutations that render Arabidopsis thaliana
MAPKs constitutively active (CA). Importantly, CA-MAPKs maintain their specificity toward known activators and substrates. As a proof-of-concept, Arabidopsis MAPK4 (MPK4) function in plant immunity was investigated. In agreement with the phenotype of mpk4 mutants, CA-MPK4 plants were compromised in pathogen-induced salicylic acid accumulation and disease resistance. MPK4 activity was found to negatively regulate pathogen-associated molecular pattern-induced reactive oxygen species production but had no impact on callose deposition, indicating that CA-MPK4 allows discriminating between processes regulated by MPK4 activity from processes indirectly affected by mpk4 mutation. Finally, MPK4 activity was also found to compromise effector-triggered immunity conditioned by the Toll Interleukin-1 Receptor–nucleotide binding (NB)–Leu-rich repeat (LRR) receptors RPS4 and RPP4 but not by the coiled coil–NB-LRR receptors RPM1 and RPS2. Overall, these data reveal important insights on how MPK4 regulates plant defenses and establishes that CA-MAPKs offer a powerful tool to analyze the function of plant MAPK pathways. 相似文献
957.
Dehne N Kerkweg U Otto T Fandrey J 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(4):R1693-R1701
Hypoxia-inducible factor (HIF) plays an important role in regulating gene expression in response to ischemia. Although activation of HIF-1 in muscle tissue was found during ischemia in vivo, the meaning and mechanisms in isolated cells are still incompletely understood. We studied activation of HIF-1 in skeletal muscle cells cultured in either their undifferentiated myoblast state or differentiated into myotubes. HIF-1 was activated in myoblasts and myotubes by hypoxia and simulated ischemia. Induction of adrenomedullin mRNA and, to a lesser extent, VEGF mRNA correlated well with the induction of HIF-1alpha protein in both cell types. Enzymes of glycolysis-like lactate dehydrogenase and pyruvate kinase showed upregulation of their mRNA only under hypoxic conditions but not during simulated ischemia. Phosphofructokinase mRNA showed no significant upregulation at all. Although HIF-1 was activated in myotubes during simulated ischemia, myotubes died preceded by a loss of ATP. Myoblasts survived simulated ischemia with no decrease in ATP or ATP turnover. Furthermore, pharmacological inhibition of HIF-1 hydroxylases by dimethyloxalylglycine (DMOG) increased HIF-1alpha accumulation and significantly upregulated the expression of adrenomedullin, VEGF, lactate dehydrogenase, and pyruvate kinase in myoblasts and myotubes. However, DMOG provided no protection from cell death. Our data indicate that HIF-1, although activated in myotubes during simulated ischemia, cannot protect against the loss of ATP and cell viability. In contrast, myoblasts survive ischemia and thus may play an important role during regeneration and HIF-1-induced revascularization. 相似文献
958.
Liliana Belmonte Stéphanie Beutheu Youmba Nathalie Bertiaux-Vanda?le Michel Antonietti Stéphane Lecleire Alberto Zalar Guillaume Gourcerol Anne-Marie Leroi Pierre Déchelotte Mo?se Co?ffier Philippe Ducrotté 《PloS one》2012,7(8)
Background
The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost. Recent studies suggest that low grade mucosal immune activation, increased intestinal permeability and the altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However, the understanding of the precise molecular pathophysiology remains largely unknown.Methodology and Findings
In this study our objective was to evaluate the TLR expression as a key player in the innate immune response, in the colonic mucosa of IBS patients classified into the three main subtypes (with constipation, with diarrhea or mixed). TLR2 and TLR4 mRNA expression was assessed by real time RT-PCR while TLRs protein expression in intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokine production was investigated by the multiplex technology. Here we report that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore, these expressions were localized in the epithelial cells, opening new perspectives for a potential role of epithelial cells in host-immune interactions in IBS. In addition, the increased TLR expression in IBS-M patients elicited intracellular signaling pathways resulting in increased expression of the mucosal proinflammatory cytokines IL-8 and IL1β.Conclusions
Our results provide the first evidence of differential expression of TLR in IBS patients according to the disease subtype. These results offer further support that microflora plays a central role in the complex pathophysiology of IBS providing novel pharmacological targets for this chronic gastrointestinal disorder according to bowel habits. 相似文献959.
Julie Jaquiéry Solenn Stoeckel Chloé Larose Pierre Nouhaud Claude Rispe Lucie Mieuzet Jo?l Bonhomme Frédérique Mahéo Fabrice Legeai Jean-Pierre Gauthier Nathalie Prunier-Leterme Denis Tagu Jean-Christophe Simon 《PLoS genetics》2014,10(12)
Although evolutionary transitions from sexual to asexual reproduction are frequent in eukaryotes, the genetic bases of such shifts toward asexuality remain largely unknown. We addressed this issue in an aphid species where both sexual and obligate asexual lineages coexist in natural populations. These sexual and asexual lineages may occasionally interbreed because some asexual lineages maintain a residual production of males potentially able to mate with the females produced by sexual lineages. Hence, this species is an ideal model to study the genetic basis of the loss of sexual reproduction with quantitative genetic and population genomic approaches. Our analysis of the co-segregation of ∼300 molecular markers and reproductive phenotype in experimental crosses pinpointed an X-linked region controlling obligate asexuality, this state of character being recessive. A population genetic analysis (>400-marker genome scan) on wild sexual and asexual genotypes from geographically distant populations under divergent selection for reproductive strategies detected a strong signature of divergent selection in the genomic region identified by the experimental crosses. These population genetic data confirm the implication of the candidate region in the control of reproductive mode in wild populations originating from 700 km apart. Patterns of genetic differentiation along chromosomes suggest bidirectional gene flow between populations with distinct reproductive modes, supporting contagious asexuality as a prevailing route to permanent parthenogenesis in pea aphids. This genetic system provides new insights into the mechanisms of coexistence of sexual and asexual aphid lineages. 相似文献
960.
Patricia Ann Okubara Camille M. Steber Victor L. DeMacon Nathalie L. Walter Timothy C. Paulitz Kimberlee K. Kidwell 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2009,119(2):293-303
The necrotrophic root pathogens Rhizoctonia solani AG-8 and R. oryzae cause Rhizoctonia root rot and damping-off, yield-limiting diseases that pose barriers to the adoption of conservation tillage
in wheat production systems. Existing control practices are only partially effective, and natural genetic resistance to Rhizoctonia has not been identified in wheat or its close relatives. We report the first genetic resistance/tolerance to R. solani AG-8 and R. oryzae in wheat (Triticum aestivum L. em Thell) germplasm ‘Scarlet-Rz1’. Scarlet-Rz1 was derived from the allohexaploid spring wheat cultivar Scarlet using
EMS mutagenesis. Tolerant seedlings displayed substantial root and shoot growth after 14 days in the presence of 100–400 propagules
per gram soil of R. solani AG-8 and R. oryzae in greenhouse assays. BC2F4 individuals of Scarlet-Rz1 showed a high and consistent degree of tolerance. Seedling tolerance was transmissible and appeared
to be dominant or co-dominant. Scarlet-Rz1 is a promising genetic resource for developing Rhizoctonia-tolerant wheat cultivars because the tolerance trait immediately can be deployed into wheat breeding germplasm through cross-hybridization,
thereby avoiding difficulties with transfer from secondary or tertiary relatives as well as constraints associated with genetically
modified plants. Our findings also demonstrate the utility of chemical mutagenesis for generating tolerance to necrotrophic
pathogens in allohexaploid wheat.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
P. A. Okubara and C. M. Steber contributed equally to this work. 相似文献