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41.
WW or WoW: the WW domains in a union of bliss 总被引:1,自引:0,他引:1
WW domains are small protein modules that recognize proline-rich peptide motifs or phosphorylated-serine/threonine proline sites in cognate proteins. Within host proteins these modules are joined to other protein domains or to a variety of catalytic domains acting together as adaptors or targeting anchors of enzymes. An important aspect of signaling by WW domains is their ability to recognize their cognate ligands in tandem. Tandem WW domains not only act in a synergistic manner but also appear to chaperone the function of each other. In this review, we focus on structure, function, and mechanism of the tandem WW domains co-operativity as well as independent actions. We emphasize here the implications of tandem arrangement and cooperative function of the domains for signaling pathways. 相似文献
42.
Vermassen E Fissore RA Nadif Kasri N Vanderheyden V Callewaert G Missiaen L Parys JB De Smedt H 《Biochemical and biophysical research communications》2004,319(3):888-893
The various inositol 1,4,5-trisphosphate receptor (IP(3)R) isoforms are potential substrates for several protein kinases. We compared the in vitro phosphorylation of purified IP(3)R1 and IP(3)R3 by the catalytic subunit of protein kinase C (PKC). Phosphorylation of IP(3)R1 by PKC was about eight times stronger than that of IP(3)R3 under identical conditions. Protein kinase A strongly stimulated the PKC-induced phosphorylation of IP(3)R1. In contrast, Ca(2+) inhibited its phosphorylation (IC(50)相似文献
43.
Volcke C Pirotton S Grandfils Ch Humbert C Thiry PA Ydens I Dubois P Raes M 《Journal of biotechnology》2006,125(1):11-21
Atomic force microscopy (AFM) is used to describe the formation process of polymer/DNA complexes. Two main objectives of this research are presented. The first one is to apply AFM as an effective tool to analyse DNA molecules and different polycation/DNA complexes in order to evaluate their degree of condensation (size and shape). The other one is to search for a relationship between the condensation state of DNA and its transfection efficiency. In this study, linear methacrylate based polymers and globular SuperFect polymers are used in order to induce DNA condensation. Ternary complexes, composed of methacrylate based polymers and polyethylene glycol (PEG)-based copolymers, are also investigated. AFM allows us to confirm good condensation conditions and relate them (or not) to transfection efficiencies. These AFM results (obtained after drying in air) are compared with measurements deduced from Dynamic Light Scattering (DLS) experiments performed in water. This comparison allowed us to identify the structural modifications resulting from deposition on the mica surface. 相似文献
44.
Colonization of tomato root by pathogenic and nonpathogenic Fusarium oxysporum strains inoculated together and separately into the soil 总被引:1,自引:0,他引:1
Olivain C Humbert C Nahalkova J Fatehi J L'Haridon F Alabouvette C 《Applied and environmental microbiology》2006,72(2):1523-1531
In soil, fungal colonization of plant roots has been traditionally studied by indirect methods such as microbial isolation that do not enable direct observation of infection sites or of interactions between fungal pathogens and their antagonists. Confocal laser scanning microscopy was used to visualize the colonization of tomato roots in heat-treated soil and to observe the interactions between a nonpathogenic strain, Fo47, and a pathogenic strain, Fol8, inoculated onto tomato roots in soil. When inoculated separately, both fungi colonized the entire root surface, with the exception of the apical zone. When both strains were introduced together, they both colonized the root surface and were observed at the same locations. When Fo47 was introduced at a higher concentration than Fol8, it colonized much of the root surface, but hyphae of Fol8 could still be observed at the same location on the root. There was no exclusion of the pathogenic strain by the presence of the nonpathogenic strain. These results are not consistent with the hypothesis that specific infection sites exist on the root for Fusarium oxysporum and instead support the hypothesis that competition occurs for nutrients rather than for infection sites. 相似文献
45.
Mochel F Durant B Meng X O'Callaghan J Yu H Brouillet E Wheeler VC Humbert S Schiffmann R Durr A 《The Journal of biological chemistry》2012,287(2):1361-1370
Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in Hdh(Q111/+) mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool. 相似文献
46.
Humbert IA Lokhande A Christopherson H German R Stone A 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,112(10):1698-1705
Before a bolus is pushed into the pharynx, oral sensory processing is critical for planning movements of the subsequent pharyngeal swallow, including hyoid bone and laryngeal (hyo-laryngeal) kinematics. However, oral and pharyngeal sensory processing for hyo-laryngeal kinematics is not fully understood. In 11 healthy adults, we examined changes in kinematics with sensory adaptation, sensitivity shifting, with oropharyngeal swallows vs. pharyngeal swallows (no oral processing), and with various bolus volumes and tastes. Only pharyngeal swallows showed sensory adaptation (gradual changes in kinematics with repeated exposure to the same bolus). Conversely, only oropharyngeal swallows distinguished volume differences, whereas pharyngeal swallows did not. No taste effects were observed for either swallow type. The hyo-laryngeal kinematics were very similar between oropharyngeal swallows and pharyngeal swallows with a comparable bolus. Sensitivity shifting (changing sensory threshold for a small bolus when it immediately follows several very large boluses) was not observed in pharyngeal or oropharyngeal swallowing. These findings indicate that once oral sensory processing has set a motor program for a specific kind of bolus (i.e., 5 ml water), hyo-laryngeal movements are already highly standardized and optimized, showing no shifting or adaptation regardless of repeated exposure (sensory adaptation) or previous sensory experiences (sensitivity shifting). Also, the oral cavity is highly specialized for differentiating certain properties of a bolus (volume) that might require a specific motor plan to ensure swallowing safety, whereas the pharyngeal cavity does not make the same distinctions. Pharyngeal sensory processing might not be able to adjust motor plans created by the oral cavity once the swallow has already been triggered. 相似文献
47.
During cyanobacterial blooms, processes influencing the population dynamics of blooming species remain partially unexplained. To provide new information, we performed a high-frequency monitoring – every 2 days at six sampling points – of a Microcystis aeruginosa population blooming in a shallow lake. At each sampling date, there was no spatial heterogeneity in the ITS genotypic composition of the population and in the proportion of potentially microcystin- producing (mcyB+) cells, whereas high variations were recorded in cell abundances. In contrast, when looking at the temporal evolution of these parameters, the ITS genotypic composition of the population and in a lesser extent the percentage of mcyB+ cells displayed high variations during the growth phase of the bloom, but not during the plateau phase or the subsequent decline. This suggests that during the development of the bloom, there was no directional selection leading to the dominance of a restricted number of genotypes and that a balancing selection process permitted the maintenance of a high genetic diversity in the Microcystis population. Finally, no relationship was found between these variations occurring in the Microcystis population and those recorded for several environmental parameters, suggesting that many factors and processes interacting together might be involved in these variations. 相似文献
48.
Van Nieuwenhove L Büscher P Balharbi F Humbert M Dieltjens T Guisez Y Lejon V 《PLoS neglected tropical diseases》2012,6(6):e1682
Background
At present, screening of the population at risk for gambiense human African trypanosomiasis (HAT) is based on detection of antibodies against native variant surface glycoproteins (VSGs) of Trypanosoma brucei (T.b.) gambiense. Drawbacks of these native VSGs include culture of infective T.b. gambiense trypanosomes in laboratory rodents, necessary for production, and the exposure of non-specific epitopes that may cause cross-reactions. We therefore aimed at identifying peptides that mimic epitopes, hence called “mimotopes,” specific to T.b. gambiense VSGs and that may replace the native proteins in antibody detection tests.Methodology/Principal Findings
A Ph.D.-12 peptide phage display library was screened with polyclonal antibodies from patient sera, previously affinity purified on VSG LiTat 1.3 or LiTat 1.5. The peptide sequences were derived from the DNA sequence of the selected phages and synthesised as biotinylated peptides. Respectively, eighteen and twenty different mimotopes were identified for VSG LiTat 1.3 and LiTat 1.5, of which six and five were retained for assessment of their diagnostic performance. Based on alignment of the peptide sequences on the original protein sequence of VSG LiTat 1.3 and 1.5, three additional peptides were synthesised. We evaluated the diagnostic performance of the synthetic peptides in indirect ELISA with 102 sera from HAT patients and 102 endemic negative controls. All mimotopes had areas under the curve (AUCs) of ≥0.85, indicating their diagnostic potential. One peptide corresponding to the VSG LiTat 1.3 protein sequence also had an AUC of ≥0.85, while the peptide based on the sequence of VSG LiTat 1.5 had an AUC of only 0.79.Conclusions/Significance
We delivered the proof of principle that mimotopes for T.b. gambiense VSGs, with diagnostic potential, can be selected by phage display using polyclonal human antibodies. 相似文献49.
Humbert O Davis L Maizels N 《Critical reviews in biochemistry and molecular biology》2012,47(3):264-281
Many devastating human diseases are caused by mutations in a single gene that prevent a somatic cell from carrying out its essential functions, or by genetic changes acquired as a result of infectious disease or in the course of cell transformation. Targeted gene therapies have emerged as potential strategies for treatment of such diseases. These therapies depend upon rare-cutting endonucleases to cleave at specific sites in or near disease genes. Targeted gene correction provides a template for homology-directed repair, enabling the cell's own repair pathways to erase the mutation and replace it with the correct sequence. Targeted gene disruption ablates the disease gene, disabling its function. Gene targeting can also promote other kinds of genome engineering, including mutation, insertion, or gene deletion. Targeted gene therapies present significant advantages compared to approaches to gene therapy that depend upon delivery of stably expressing transgenes. Recent progress has been fueled by advances in nuclease discovery and design, and by new strategies that maximize efficiency of targeting and minimize off-target damage. Future progress will build on deeper mechanistic understanding of critical factors and pathways. 相似文献
50.
D Rainteau L Humbert E Delage C Vergnolle C Cantrel MA Maubert S Lanfranchi R Maldiney S Collin C Wolf A Zachowski E Ruelland 《PloS one》2012,7(7):e41985