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31.
Erik Ziegler Ariane Foret Laura Mascetti Vincenzo Muto Anahita Le Bourdiec-Shaffii Johan Stender Evelyne Balteau Vinciane Dideberg Vincent Bours Pierre Maquet Christophe Phillips 《PloS one》2013,8(7)
Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin''s activity-dependent release. We used diffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear differences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classifier capable of identifying the subjects'' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor, and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture. 相似文献
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Moreau D Burstin J Aubert G Huguet T Ben C Prosperi JM Salon C Munier-Jolain N 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2012,124(4):755-768
Medicago truncatula is used as a model plant for exploring the genetic and molecular determinants of nitrogen (N) nutrition in legumes. In this
study, our aim was to detect quantitative trait loci (QTL) controlling plant N nutrition using a simple framework of carbon/N
plant functioning stemming from crop physiology. This framework was based on efficiency variables which delineated the plant’s
efficiency to take up and process carbon and N resources. A recombinant inbred line population (LR4) was grown in a glasshouse
experiment under two contrasting nitrate concentrations. At low nitrate, symbiotic N2 fixation was the main N source for plant growth and a QTL with a large effect located on linkage group (LG) 8 affected all
the traits. Significantly, efficiency variables were necessary both to precisely localize a second QTL on LG5 and to detect
a third QTL involved in epistatic interactions on LG2. At high nitrate, nitrate assimilation was the main N source and a larger
number of QTL with weaker effects were identified compared to low nitrate. Only two QTL were common to both nitrate treatments:
a QTL of belowground biomass located at the bottom of LG3 and another one on LG6 related to three different variables (leaf
area, specific N uptake and aboveground:belowground biomass ratio). Possible functions of several candidate genes underlying
QTL of efficiency variables could be proposed. Altogether, our results provided new insights into the genetic control of N
nutrition in M. truncatula. For instance, a novel result for M. truncatula was identification of two epistatic interactions in controlling plant N2 fixation. As such this study showed the value of a simple conceptual framework based on efficiency variables for studying
genetic determinants of complex traits and particularly epistatic interactions. 相似文献
37.
Funamoto S Anjard C Nellen W Ochiai H 《Differentiation; research in biological diversity》2003,71(1):51-61
In eukaryotic cells, the universal second messenger cAMP regulates various aspects of development and differentiation. The primary target for cAMP is the regulatory subunit of cAMP-dependent protein kinase A (PKA), which, upon cAMP binding, dissociates from the catalytic subunit and thus activates it. In the soil amoeba Dictyostelium discoideum, the function of PKA in growth, development and cell differentiation has been thoroughly investigated and substantial information is available. To obtain a more general view, we investigated the influence of PKA on development of the related species Polysphondylium pallidum. Cells were transformed to overexpress either a dominant negative mutant of the regulatory subunit (Rm) from Dictyostelium that cannot bind cAMP, or the catalytic subunit (PKA-C) from Dictyostelium. Cells overexpressing Rm rarely aggregated and the few multicellular structures developed slowly into very small fruiting bodies without branching of secondary sorogens, the prominent feature of Polysphondylium. Few round spores with reduced viability were formed. When mixed with wild-type cells and allowed to develop, the Rm cells were randomly distributed in aggregation streams, but were later found in the posterior region of the culminating slug or were left behind on the surface of the substratum. The PKA-C overexpressing cells exhibited precocious development and formed more aggregates of smaller size. Moreover, expression of PKA-C under the control of the prestalk-specific ecmB promoter of Dictyostelium leads to protrusions from aggregation streams. We conclude that Dictyostelium PKA subunits introduced into Polysphondylium cells are functional as signal components, indicating that a biochemically similar PKA mechanism works in Polysphondylium. 相似文献
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Lucie Guetzoyan Xiao-Min Yu Florence Ramiandrasoa Stéphanie Pethe Christophe Rogier Bruno Pradines Thierry Cresteil Martine Perrée-Fauvet Jean-Pierre Mahy 《Bioorganic & medicinal chemistry》2009,17(23):8032-8039
A series of acridine derivatives were synthesised and their in vitro antimalarial activity was evaluated against one chloroquine-susceptible strain (3D7) and three chloroquine-resistant strains (W2, Bre1 and FCR3) of Plasmodium falciparum. Structure–activity relationship showed that two positives charges as well as 6-chloro and 2-methoxy substituents on the acridine ring were required to exert a good antimalarial activity. The best compounds possessing these features inhibited the growth of the chloroquine-susceptible strain with an IC50 ? 0.07 μM, close to that of chloroquine itself, and that of the three chloroquine-resistant strains better than chloroquine with IC50 ? 0.3 μM. These acridine derivatives inhibited the formation of β-hematin, suggesting that, like CQ, they act on the haem crystallization process. Finally, in vitro cytotoxicity was also evaluated upon human KB cells, which showed that one of them 9-(6-ammonioethylamino)-6-chloro-2-methoxyacridinium dichloride 1 displayed a promising antimalarial activity in vitro with a quite good selectivity index versus mammalian cell on the CQ-susceptible strain and promising selectivity on other strains. 相似文献
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Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents 下载免费PDF全文
Mineur P Colige AC Deroanne CF Dubail J Kesteloot F Habraken Y Noël A Vöö S Waltenberger J Lapière CM Nusgens BV Lambert CA 《The Journal of cell biology》2007,179(6):1261-1273
Ultraviolet B and genotoxic drugs induce the expression of a vascular endothelial growth factor A (VEGF-A) splice variant (VEGF111) encoded by exons 1–4 and 8 in many cultured cells. Although not detected in a series of normal human and mouse tissue, VEGF111 expression is induced in MCF-7 xenografts in nude mice upon treatment by camptothecin. The skipping of exons that contain proteolytic cleavage sites and extracellular matrix–binding domains makes VEGF111 diffusible and resistant to proteolysis. Recombinant VEGF111 activates VEGF receptor 2 (VEGF-R2) and extracellularly regulated kinase 1/2 in human umbilical vascular endothelial cells and porcine aortic endothelial cells expressing VEGF-R2. The mitogenic and chemotactic activity and VEGF111's ability to promote vascular network formation during embyonic stem cell differentiation are similar to those of VEGF121 and 165. Tumors in nude mice formed by HEK293 cells expressing VEGF111 develop a more widespread network of numerous small vessels in the peritumoral tissue than those expressing other isoforms. Its potent angiogenic activity and remarkable resistance to proteolysis makes VEGF111 a potential adverse factor during chemotherapy but a beneficial therapeutic tool for ischemic diseases. 相似文献