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71.
p53 is a human tumour suppressor which regulates multiple cellular processes, including cell growth, genomic stability and cell death. Recent works have demonstrated the bacterial redox protein azurin to enter cancer cells and induce apoptosis through p53 stabilization, resulting in a tumour growth regression. Azurin has been shown to bind p53 although many details of the complex formed by these two proteins are still poorly characterized. Here, we get insight into the kinetics of this complex formation, by exploring the interaction between p53 and azurin in their environment by single molecule force spectroscopy. To this aim, azurin has been linked to the atomic force microscope tip, whereas p53 has been immobilized onto a gold substrate. Therefore, by performing force-distance cycles we have detected specific recognition events between p53 and azurin, displaying unbinding forces of around 70 pN for an applied loading rate of 3 nN s(-1). The specificity of these events has been assessed by the significant reduction of their frequency observed after blocking the p53 sample by an azurin solution. Moreover, by measuring the rupture force as a function of the loading rate we have determined the dissociation rate constant of this complex to be approximately 0.1 s(-1). Our findings are here discussed in connection with results obtained in bulk experiments, with the aim of clarifying some molecular details of the p53-azurin complex that may help designing new anticancer strategy. 相似文献
72.
Robert Caesar Monia Manieri Thomas Kelder Mark Boekschoten Chris Evelo Michael Müller Teake Kooistra Saverio Cinti Robert Kleemann Christian A. Drevon 《PloS one》2010,5(7)
Depot-dependent differences in adipose tissue physiology may reflect specialized functions and local interactions between adipocytes and surrounding tissues. We combined time-resolved microarray analyses of mesenteric- (MWAT), subcutaneous- (SWAT) and epididymal adipose tissue (EWAT) during high-fat feeding of male transgenic ApoE3Leiden mice with histology, targeted lipidomics and biochemical analyses of metabolic pathways to identify differentially regulated processes and site-specific functions. EWAT was found to exhibit physiological zonation. De novo lipogenesis in fat proximal to epididymis was stably low, whereas de novo lipogenesis distal to epididymis and at other locations was down-regulated in response to high-fat diet. The contents of linoleic acid and α-linolenic acid in EWAT were increased compared to other depots. Expression of the androgen receptor (Ar) was higher in EWAT than in MWAT and SWAT. We suggest that Ar may mediate depot-dependent differences in de novo lipogenesis rate and propose that accumulation of linoleic acid and α-linolenic acid in EWAT is favored by testosterone-mediated inhibition of de novo lipogenesis and may promote further elongation and desaturation of these polyunsaturated fatty acids during spermatogenesis. 相似文献
73.
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75.
Two pine species (Pinus resinosa, P. banksiana) responded to inoculation with fungi carried by bark beetles by rapidly increasing monoterpene concentrations at the entry site. Changes in total monoterpenes were more pronounced than changes in proportionate compositions. The extent and rate of host response was affected by fungal species, the viability of the inoculum, and host tree species. In general, host responses were highest to fungi that are phytopathogenic and consistently associated with the major bark beetles in the study region. Simple mechanical wounding cannot account for the observed allelochemical changes, as aseptic inoculations elicited only minor reactions. Similarly, inoculation with autoclaved inviable fungi generally elicited intermediate responses, suggesting that both structural and metabolic fungal properties are important. Responses by jack pine, P. banksiana, were generally more rapid and variable than those of red pine, P. resinosa. Dose-toxicity experiments with synthetic compounds demonstrated that monoterpene concentrations present in vivo only a few days after simulated attack are lethal to most beetles. Constitutive (pre-attack) monoterpene levels can also exert some toxicity. Because bark beetles engage in pheromone-mediated mass attacks that can deplete host defenses, constitutive monoterpene levels, while a necessary early phase of successful plant defense, appear insufficient by themselves. Such interactions between constitutive and induced defense chemistry may be important considerations when evaluating general theories of plant defense. 相似文献
76.
Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway. 总被引:7,自引:0,他引:7
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77.
Deciduous larches, Larix spp., and evergreen pines, Pinus spp., are sympatric Pinaceae conifers. Adjacent monocultures of 10-year-old Larix decidua Mill. and Pinus resinosa Ait. were subjected to single-season artificial defoliation by clipping from 0% to 99% of each needle. Survival, above-ground
productivity, and architecture were measured for 36 months. P. resinosa and L. decidua exhibited differential relationships with defoliation intensity and recovery time. Two months after treatment, defoliation
reduced larch height growth but had no effect on radial growth. By contrast, P. resinosa stem radial growth was reduced immediately, but height growth was not decreased until the following year. Pine leader growth
and above-ground biomass following 66% defoliation never recovered to control values or 33% defoliated pines. Conversely,
defoliated larch quickly recovered from an initial growth loss to eliminate all treatment effects on biomass. The plasticity
in architectural response found in larch, but not pine, might partially account for defoliation tolerance. Both P. resinosa and L. decidua exhibited non-linear responses to defoliation. These patterns may be caused partially by the uneven distribution of nutrients
within needles, rather than a simple function of leaf area lost to defoliators. Concentrations of 13 nutrients in P. resinosa were highest either in the mid- (Ca, Mg, S, Zn, B, Mn, Fe, Al and Na) or basal- (N, P, K, and Cu) section. The relatively
low nutrient content in needle tips may contribute to similar biomass productivity between trees defoliated 33% and controls.
Removal of needle mid-sections significantly reduced whole-plant productivity. In contrast, L. decidua nutrients are concentrated in the distal sections. Nutrient concentrations were generally highest in larch. Our results agree
with an emergent prediction of the carbon/nutrient balance theory that defoliation more severely reduces growth of evergreen
than deciduous species. These results are discussed within the physiological, ecological and evolutionary context of allocation
theory, with implications for natural resource management and plant-insect interaction theory.
Received: 6 April 1995 / Accepted: 29 August 1995 相似文献
78.
Sara Artusi Rosalba Perrone Sara Lago Paolo Raffa Enzo Di?Iorio Giorgio Palù Sara N. Richter 《Nucleic acids research》2016,44(21):10343-10353
We have previously shown that clusters of guanine quadruplex (G4) structures can form in the human herpes simplex-1 (HSV-1) genome. Here we used immunofluorescence and immune-electron microscopy with a G4-specific monoclonal antibody to visualize G4 structures in HSV-1 infected cells. We found that G4 formation and localization within the cells was virus cycle dependent: viral G4s peaked at the time of viral DNA replication in the cell nucleus, moved to the nuclear membrane at the time of virus nuclear egress and were later found in HSV-1 immature virions released from the cell nucleus. Colocalization of G4s with ICP8, a viral DNA processing protein, was observed in viral replication compartments. G4s were lost upon treatment with DNAse and inhibitors of HSV-1 DNA replication. The notable increase in G4s upon HSV-1 infection suggests a key role of these structures in the HSV-1 biology and indicates new targets to control both the lytic and latent infection. 相似文献
79.
Correlation between study units in quantitative genetics studies often makes it difficult to compare important inferential aspects of studies. Describing the relatedness between study units is critical to capture features of pedigree studies involving heritability, including power and precision of heritability estimates. Blangero et al. (Adv Genet 81:1–31, 2012) showed that in pedigree studies the power to detect heritability is a function of the true heritability and the eigenvalues of the kinship matrix. We extend this to a more general setting which allows statements about expected precision of heritability estimates. Using two different Taylor series approximations, we summarize the relatedness in a study design by one or two parameters. These relatedness summary parameters (RSPs) are functions of the eigenvalues or log-eigenvalues of the kinship matrix. Using the RSPs based on the log-eigenvalues, we accurately approximate the expectation of the likelihood ratio test and expected confidence interval widths. We define an effective sample size of a target study as one which has the equivalent power and precision to a reference design. Using unrelated sibpairs as the reference design provides very accurate assessments of power. RSPs and effective sample sizes provide new tools for comparing studies and communicating information about relatedness in heritability studies. 相似文献
80.
Sabrina Donzelli Fabio Zaina Monia Lusini Salvatore Minnella Stefano Respizzi Luca Balzarini Salvatore Poma Stefano Negrini 《Scoliosis》2016,11(2):34