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31.
p21-activated kinases (PAKs) associate with a guanine nucleotide exchange factor, Pak-interacting exchange factor (PIX), which in turn binds the paxillin-associated adaptor GIT1 that targets the complex to focal adhesions. Here, a detailed structure-function analysis of GIT1 reveals how this multidomain adaptor also participates in activation of PAK. Kinase activation does not occur via Cdc42 or Rac1 GTPase binding to PAK. The ability of GIT1 to stimulate alphaPAK autophosphorylation requires the participation of the GIT N-terminal Arf-GAP domain but not Arf-GAP activity and involves phosphorylation of PAK at residues common to Cdc42-mediated activation. Thus, the activation of PAK at adhesion complexes involves a complex interplay between the kinase, Rho GTPases and protein partners that provide localization cues. 相似文献
32.
Sergio Arancibia Cecilia Espinoza Fabián Salazar Miguel Del Campo Ricardo Tampe Ta-Ying Zhong Pablo De Ioannes Bruno Moltedo Jorge Ferreira Ed C. Lavelle Augusto Manubens Alfredo E. De Ioannes María Inés Becker 《PloS one》2014,9(1)
Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropod Fissurella latimarginata (FLH). This protein has the typical hollow, cylindrical structure of other known hemocyanins, such as the keyhole limpet hemocyanin (KLH) and the Concholepas hemocyanin (CCH). FLH, like the KLH isoforms, is composed of a single type of polypeptide with exposed N- and O-linked oligosaccharides. However, its immunogenicity was significantly greater than that of KLH and CCH, as FLH induced a stronger humoral immune response and had more potent anti-tumor activity, delaying tumor growth and increasing the survival of mice challenged with B16F10 melanoma cells, in prophylactic and therapeutic settings. Additionally, FLH-treated mice demonstrated increased IFN-γ production and higher numbers of tumor-infiltrating CD4+ lymphocytes. Furthermore, in vitro assays demonstrated that FLH, but not CCH or KLH, stimulated the rapid production of pro-inflammatory cytokines (IL-6, IL-12, IL-23 and TNF-α) by dendritic cells, triggering a pro-inflammatory milieu that may explain its enhanced immunological activity. Moreover, this effect was abolished when deglycosylated FLH was used, suggesting that carbohydrates play a crucial role in the innate immune recognition of this protein. Altogether, our data demonstrate that FLH possesses increased anti-tumor activity in part because it activates a more potent innate immune response in comparison to other known hemocyanins. In conclusion, FLH is a potential new marine adjuvant for immunization and possible cancer immunotherapy. 相似文献
33.
Purpose
The aim of this study was to develop a robust post-processing workflow for motion-corrupted datasets in diffusion kurtosis imaging (DKI).Materials and methods
The proposed workflow consisted of brain extraction, rigid registration, distortion correction, artifacts rejection, spatial smoothing and tensor estimation. Rigid registration was utilized to correct misalignments. Motion artifacts were rejected by using local Pearson correlation coefficient (LPCC). The performance of LPCC in characterizing relative differences between artifacts and artifact-free images was compared with that of the conventional correlation coefficient in 10 randomly selected DKI datasets. The influence of rejected artifacts with information of gradient directions and b values for the parameter estimation was investigated by using mean square error (MSE). The variance of noise was used as the criterion for MSEs. The clinical practicality of the proposed workflow was evaluated by the image quality and measurements in regions of interest on 36 DKI datasets, including 18 artifact-free (18 pediatric subjects) and 18 motion-corrupted datasets (15 pediatric subjects and 3 essential tremor patients).Results
The relative difference between artifacts and artifact-free images calculated by LPCC was larger than that of the conventional correlation coefficient (p<0.05). It indicated that LPCC was more sensitive in detecting motion artifacts. MSEs of all derived parameters from the reserved data after the artifacts rejection were smaller than the variance of the noise. It suggested that influence of rejected artifacts was less than influence of noise on the precision of derived parameters. The proposed workflow improved the image quality and reduced the measurement biases significantly on motion-corrupted datasets (p<0.05).Conclusion
The proposed post-processing workflow was reliable to improve the image quality and the measurement precision of the derived parameters on motion-corrupted DKI datasets. The workflow provided an effective post-processing method for clinical applications of DKI in subjects with involuntary movements. 相似文献34.
35.
Colin Brent Christian Peeters Vincent Dietemann Robin Crewe Ed Vargo 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2006,192(3):315-320
In colonies of the queenless ant Streblognathus peetersi, dominance interactions produce a reproductive hierarchy in which one individual, the alpha, is capable of producing offspring while her subordinates remain infertile. Based on differences between behaviour and cuticular hydrocarbon profiles, the subordinates can be further divided into high and low ranking workers. Although it had been shown previously that alphas treated with a juvenile hormone analog lose their reproductive status, little was known of the endocrinological basis of dominance in this species. To elucidate the underlying endocrinology of these three ranks, we measured the individual in vitro rate of juvenile hormone (JH) production of excised corpora allata, and the ecdysteroid titer of pooled hemolymph samples. Production of JH was highest in low-ranking workers, intermediate in high rankers, and almost undetectable in alphas. Ecdysteroid titers were low for low rankers, but were more than twice as high for both high rankers and alphas. The results support the hypothesis that JH suppresses ovarian function in these queenless ants, and suggest that ecdysteroids may be responsible for stimulating vitellogenin production. The possible role of these hormones as behavioural modulators is also discussed. 相似文献
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37.
Substrate and product inhibition of hydrogen production by the extreme thermophile,Caldicellulosiruptor saccharolyticus 总被引:3,自引:0,他引:3
Substrate and product inhibition of hydrogen production during sucrose fermentation by the extremely thermophilic bacterium Caldicellulosiruptor saccharolyticus was studied. The inhibition kinetics were analyzed with a noncompetitive, nonlinear inhibition model. Hydrogen was the most severe inhibitor when allowed to accumulate in the culture. Concentrations of 5-10 mM H(2) in the gas phase (identical with partial hydrogen pressure (pH(2)) of (1-2) x 10(4) Pa) initiated a metabolic shift to lactate formation. The extent of inhibition by hydrogen was dependent on the density of the culture. The highest tolerance for hydrogen was found at low volumetric hydrogen production rates, as occurred in cultures with low cell densities. Under those conditions the critical hydrogen concentration in the gas phase was 27.7 mM H(2) (identical with pH(2) of 5.6 x 10(4) Pa); above this value hydrogen production ceased completely. With an efficient removal of hydrogen sucrose fermentation was mainly inhibited by sodium acetate. The critical concentrations of sucrose and acetate, at which growth and hydrogen production was completely inhibited (at neutral pH and 70 degrees C), were 292 and 365 mM, respectively. Inorganic salts, such as sodium chloride, mimicked the effect of sodium acetate, implying that ionic strength was responsible for inhibition. Undissociated acetate did not contribute to inhibition of cultures at neutral or slightly acidic pH. Exposure of exponentially growing cultures to concentrations of sodium acetate or sodium chloride higher than ca. 175 mM caused cell lysis, probably due to activation of autolysins. 相似文献
38.
Rooseboom M Vermeulen NP Groot EJ Commandeur JN 《Chemico-biological interactions》2002,140(3):243-264
Selenocysteine Se-conjugates (e.g. methylselenocysteine) have been shown to be potent chemopreventive and chemoprotective agents, and inducers of apoptosis. Although the mechanism of action remains to be elucidated, beta-elimination of these compounds by beta-lyase enzymes into corresponding selenols, pyruvate and ammonia is thought to be critical. This study describes in vitro beta-lyase activity in nine rat organs using three selenocysteine Se-conjugates and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine. For all substrates the highest beta-elimination rates were found in kidney, followed by liver, while brain, spleen, heart, large and small intestine, thyroid and lung were of minor importance. Since liver plays an important role in beta-elimination, hepatic beta-lyase activity was extensively studied using 23 selenocysteine Se-conjugates and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine and was compared with previously obtained renal beta-lyase data. The results showed that hepatic beta-lyase activities were 4-25-fold lower than the corresponding renal beta-lyase activities. Hepatic beta-elimination of the substrates appeared to be exclusively catalyzed by the pyridoxal 5'-phosphate-dependent beta-lyase enzyme kynureninase. Studies performed with human hepatic cytosols of three individuals showed that hepatic beta-lyase activity was 2-5-fold higher when compared with the previously obtained human renal activity. Significant correlation was obtained between human hepatic beta-lyase activities of three individuals. The relevance of this data for using SeCys-conjugates as chemopreventive and a chemoprotective agent is discussed. Based on the large differences in organ-selective beta-elimination and specific beta-lyase activity between rat and humans, the rat might not be a good model to investigate nephrotoxicity of cysteine S-conjugates, and chemoprevention and chemoprotection of SeCys-conjugates in man. 相似文献
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