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31.
Label‐free analysis of human cerebrospinal fluid addressing various normalization strategies and revealing protein groups affected by multiple sclerosis 下载免费PDF全文
Jill A. Opsahl Marc Vaudel Astrid Guldbrandsen Elise Aasebø Vincent Van Pesch Diego Franciotta Kjell‐Morten Myhr Harald Barsnes Magnus Berle Øivind Torkildsen Ann C. Kroksveen Frode S. Berven 《Proteomics》2016,16(7):1154-1165
The aims of the study were to: (i) identify differentially regulated proteins in cerebrospinal fluid (CSF) between multiple sclerosis (MS) patients and non‐MS controls; (ii) examine the effect of matching the CSF samples on either total protein amount or volume, and compare four protein normalization strategies for CSF protein quantification. CSF from MS patients (n = 37) and controls (n = 64), consisting of other noninflammatory neurological diseases (n = 50) and non neurological spinal anesthetic subjects (n = 14), were analyzed using label‐free proteomics, quantifying almost 800 proteins. In total, 122 proteins were significantly regulated (p < 0.05), where 77 proteins had p‐value <0.01 or AUC value >0.75. Hierarchical clustering indicated that there were two main groups of MS patients, those with increased levels of inflammatory response proteins and decreased levels of proteins involved in neuronal tissue development (n = 30), and those with normal protein levels for both of these protein groups (n = 7). The main subgroup of controls clustering with the MS patients showing increased inflammation and decreased neuronal tissue development were patients suffering from chronic fatigue. Our data indicate that the preferable way to quantify proteins in CSF is to first match the samples on total protein amount and then normalize the data based on the median intensities, preferably from the CNS‐enriched proteins. 相似文献
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Robert A. Volkmann Christopher M. Fanger David R. Anderson Venkata Ramana Sirivolu Kathy Paschetto Earl Gordon Caterina Virginio Melanie Gleyzes Bruno Buisson Esther Steidl Susanna B. Mierau Michela Fagiolini Frank S. Menniti 《PloS one》2016,11(2)
GluN2A is the most abundant of the GluN2 NMDA receptor subunits in the mammalian CNS. Physiological and genetic evidence implicate GluN2A-containing receptors in susceptibility to autism, schizophrenia, childhood epilepsy and neurodevelopmental disorders such as Rett Syndrome. However, GluN2A-selective pharmacological probes to explore the therapeutic potential of targeting these receptors have been lacking. Here we disclose a novel series of pyrazine-containing GluN2A antagonists exemplified by MPX-004 (5-(((3-chloro-4-fluorophenyl)sulfonamido)methyl)-N-((2-methylthiazol-5-yl)methyl)pyrazine-2-carboxamide) and MPX-007 (5-(((3-fluoro-4-fluorophenyl)sulfonamido)methyl)-N-((2-methylthiazol-5-yl)methyl)methylpyrazine-2-carboxamide). MPX-004 and MPX-007 inhibit GluN2A-containing NMDA receptors expressed in HEK cells with IC50s of 79 nM and 27 nM, respectively. In contrast, at concentrations that completely inhibited GluN2A activity these compounds have no inhibitory effect on GluN2B or GluN2D receptor-mediated responses in similar HEK cell-based assays. Potency and selectivity were confirmed in electrophysiology assays in Xenopus oocytes expressing GluN2A-D receptor subtypes. Maximal concentrations of MPX-004 and MPX-007 inhibited ~30% of the whole-cell current in rat pyramidal neurons in primary culture and MPX-004 inhibited ~60% of the total NMDA receptor-mediated EPSP in rat hippocampal slices. GluN2A-selectivity at native receptors was confirmed by the finding that MPX-004 had no inhibitory effect on NMDA receptor mediated synaptic currents in cortical slices from GRIN2A knock out mice. Thus, MPX-004 and MPX-007 offer highly selective pharmacological tools to probe GluN2A physiology and involvement in neuropsychiatric and developmental disorders. 相似文献
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Clinical,genetic and neuropathological findings in a series of 138 fetuses with a corpus callosum malformation 下载免费PDF全文
Caroline Alby Valérie Malan Lucile Boutaud Maria Angela Marangoni Bettina Bessières Maryse Bonniere Amale Ichkou Nadia Elkhartoufi Nadia Bahi‐Buisson Pascale Sonigo Anne‐Elodie Millischer Sophie Thomas Yves Ville Michel Vekemans Férechté Encha‐Razavi Tania Attié‐Bitach 《Birth defects research. Part A, Clinical and molecular teratology》2016,106(1):36-46
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Overcoming challenges on using native seeds for restoration of megadiverse resource‐poor environments: a reply to Madsen et al. 下载免费PDF全文
Roberta L. C. Dayrell André J. Arruda Elise Buisson Fernando A. O. Silveira 《Restoration Ecology》2016,24(6):710-713
Madsen et al. (2016) reviewed several major limiting factors to establishment of seedlings in nonforest ecosystems (NFE), and proposed seed enhancement technologies to overcome these restoration barriers. However, biodiverse nutrient‐poor NFE present additional hurdles that preclude landscape‐scale seed‐based restoration and were not mentioned in their review. Here, we discuss issues related to native seed availability and provenance, and shortfalls in knowledge on seed quality testing and dormancy release that severely hamper restoration of degraded nutrient‐impoverished NFE. We present alternatives for overcoming these challenges and highlight the need for investments to find more practical and cost‐effective options for broad‐scale restoration. 相似文献
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Comparative proteome profiling and functional analysis of chronic myelogenous leukemia cell lines 总被引:1,自引:0,他引:1
Fontana S Alessandro R Barranca M Giordano M Corrado C Zanella-Cleon I Becchi M Kohn EC De Leo G 《Journal of proteome research》2007,6(11):4330-4342
The aim of the present study was the molecular profiling of different Ph+ chronic myelogenous leukemia (CML) cell lines (LAMA84, K562, and KCL22) by a proteomic approach. By employing two-dimensional gel electrophoresis combined with mass spectrometry analysis, we have identified 191 protein spots corresponding to 142 different proteins. Among these, 63% were cancer-related proteins and 74% were described for the first time in leukemia cells. Multivariate analysis highlighted significant differences in the global proteomic profile of the three CML cell lines. In particular, the detailed analysis of 35 differentially expressed proteins revealed that LAMA84 cells preferentially expressed proteins associated with an invasive behavior, while K562 and KCL22 cells preferentially expressed proteins involved in drug resistance. These data demonstrate that these CML cell lines, although representing the same pathological phenotype, show characteristics in their protein expression profile that suggest different phenotypic leukemia subclasses. These data contribute a new potential characterization of the CML phenotype and may help to understand interpatient variability in the progression of disease and in the efficacy of a treatment. 相似文献
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Sidiky Ménil Jean-Louis Petit Elise Courvoisier-Dezord Adrien Debard Virginie Pellouin Thomas Reignier Michelle Sergent Valérie Deyris Katia Duquesne Véronique de Berardinis Véronique Alphand 《Biotechnology and bioengineering》2019,116(11):2852-2863
The efficiency of a versatile in vivo cascade involving a promiscuous alcohol dehydrogenase, obtained from a biodiversity search, and a Baeyer–Villiger monooxygenase was enhanced by the independent control of the production level of each enzyme to produce ε-caprolactone and 3,4-dihydrocoumarin. This goal was achieved by adjusting the copy number per cell of Escherichia coli plasmids. We started from the observation that this number generally correlates with the amount of produced enzyme and demonstrated that an in vivo multi-enzymatic system can be improved by the judicious choice of plasmid, the lower activity of the enzyme that drives the limiting step being counter-balanced by a higher concentration. Using a preconception-free approach to the choice of the plasmid type, we observed positive and negative synergetic effects, sometimes unexpected and depending on the enzyme and plasmid combinations. Experimental optimization of the culture conditions allowed us to obtain the complete conversion of cyclohexanol (16 mM) and 1-indanol (7.5 mM) at a 0.5-L scale. The yield for the conversion of cyclohexanol was 80% (0.7 g ε-caprolactone, for the productivity of 244 mg·L −1·h −1) and that for 1-indanol 60% (0.3 g 3,4-dihydrocoumarin, for the productivity of 140 mg·L −1·h −1). 相似文献