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Miriam Masià-Balagué Ismael Izquierdo Georgina Garrido Arnau Cordomí Laura Pérez-Benito Nichol L. G. Miller David D. Schlaepfer Véronique Gigoux Anna M. Aragay 《The Journal of biological chemistry》2015,290(24):15197-15209
The guanine nucleotide exchange factor Rgnef (also known as ArhGEF28 or p190RhoGEF) promotes colon carcinoma cell motility and tumor progression via interaction with focal adhesion kinase (FAK). Mechanisms of Rgnef activation downstream of integrin or G protein-coupled receptors remain undefined. In the absence of a recognized G protein signaling homology domain in Rgnef, no proximal linkage to G proteins was known. Utilizing multiple methods, we have identified Rgnef as a new effector for Gα13 downstream of gastrin and the type 2 cholecystokinin receptor. In DLD-1 colon carcinoma cells depleted of Gα13, gastrin-induced FAK Tyr(P)-397 and paxillin Tyr(P)-31 phosphorylation were reduced. RhoA GTP binding and promoter activity were increased by Rgnef in combination with active Gα13. Rgnef co-immunoprecipitated with activated Gα13Q226L but not Gα12Q229L. The Rgnef C-terminal (CT, 1279–1582) region was sufficient for co-immunoprecipitation, and Rgnef-CT exogenous expression prevented Gα13-stimulated SRE activity. A domain at the C terminus of the protein close to the FAK binding domain is necessary to bind to Gα13. Point mutations of Rgnef-CT residues disrupt association with active Gα13 but not Gαq. These results show that Rgnef functions as an effector of Gα13 signaling and that this linkage may mediate FAK activation in DLD-1 colon carcinoma cells. 相似文献
124.
Morten B. Hansen Michael D. Abràmoff James C. Folk Wanjiku Mathenge Andrew Bastawrous Tunde Peto 《PloS one》2015,10(10)
Objective
Digital retinal imaging is an established method of screening for diabetic retinopathy (DR). It has been established that currently about 1% of the world’s blind or visually impaired is due to DR. However, the increasing prevalence of diabetes mellitus and DR is creating an increased workload on those with expertise in grading retinal images. Safe and reliable automated analysis of retinal images may support screening services worldwide. This study aimed to compare the Iowa Detection Program (IDP) ability to detect diabetic eye diseases (DED) to human grading carried out at Moorfields Reading Centre on the population of Nakuru Study from Kenya.Participants
Retinal images were taken from participants of the Nakuru Eye Disease Study in Kenya in 2007/08 (n = 4,381 participants [NW6 Topcon Digital Retinal Camera]).Methods
First, human grading was performed for the presence or absence of DR, and for those with DR this was sub-divided in to referable or non-referable DR. The automated IDP software was deployed to identify those with DR and also to categorize the severity of DR.Main Outcome Measures
The primary outcomes were sensitivity, specificity, and positive and negative predictive value of IDP versus the human grader as reference standard.Results
Altogether 3,460 participants were included. 113 had DED, giving a prevalence of 3.3% (95% CI, 2.7–3.9%). Sensitivity of the IDP to detect DED as by the human grading was 91.0% (95% CI, 88.0–93.4%). The IDP ability to detect DED gave an AUC of 0.878 (95% CI 0.850–0.905). It showed a negative predictive value of 98%. The IDP missed no vision threatening retinopathy in any patients and none of the false negative cases met criteria for treatment.Conclusions
In this epidemiological sample, the IDP’s grading was comparable to that of human graders’. It therefore might be feasible to consider inclusion into usual epidemiological grading. 相似文献125.
Mundina M Vila R Tomi F Tomàs X Cicció JF Adzet T Casanova J Cañigueral S 《Biochemical Systematics and Ecology》2001,29(7):739-748
Essential oils obtained by hydrodistillation from leaves and spikes of Piper lanceaefolium H.B.K. of Costa Rica were analysed by GC-FID, GC-MS and 13C-NMR methods. Main constituents found in the oil from leaves were sesquiterpene hydrocarbons - especially beta-caryophyllene and germacrene D - and phenylpropanoids, of which elemicin and parsley apiol were the major ones. The volatile oil from spikes showed monoterpene hydrocarbons, namely alpha- and beta-pinene, and the same phenylpropanoids as in the oil from leaves as the major constituents. Results obtained in the analysis by GC-FID and GC-MS of the essential oils from individual plants of different geographic origin were submitted to chemometric cluster analysis and principal component analysis, showing the presence of three different types of oils (i) parsley apiol/elemicin, (ii) elemicin/parsley apiol/dill apiol, and (iii) parsley apiol/dill apiol. 相似文献
126.
Step-wise dilution of chicken thymus cell suspensions has been used to sequentially reveal suppressor, effector, and helper cells in these suspensions. The cells were tested either alone or in autologous mixture combinations with peripheral blood lymphocytes (PBL) as a source of effector cells. The assays studied were graft-vs-host reaction (GvHR) and mixed lymphocyte (MLR) reaction, spontaneous cellular cytotoxicity and antibody-dependent cell-mediated cytotoxicity, and mitogen responsiveness to Con A, PHA, and PWM. When tested alone, high numbers of thymus cells (1 X 10(7) gave weak or low responses, with the exception of GvHR, which was high. When this number of thymocytes was mixed with a strongly responding PBL effector population, there was marked suppression of the latter. Nonspecific crowding was excluded as a cause for the decreased responsiveness, and the data therefore demonstrated the presence of suppressor cells in the thymus. With gradual reduction of the thymus cell number in the mixtures, the suppressor activity was lost, but concomitant with this was the appearance of, or a gradual increase in, thymus effector cells giving good responses. Further dilutions of the thymus (to, e.g., 1 X 10(5) cells) depleted the suspension of effector cells, but helper cells capable of markedly amplifying the effector potential of PBL were revealed. The suppressor/helper function of the thymus was not only dependent on the absolute numbers of thymus cells present, but also on the degree of inherent responsiveness of the effector PBL. If the response of PBL alone was strong, a thymus suspension containing both helper and suppressor cells (e.g., 1 X 10(6) cells) caused suppression of the PBL; if the PBL alone were weak, this same thymus cell suspension caused enhancement. The outcome of an immune response is therefore dependent not only on the presence or absence of particular cell types, but also on the ratios between these cells. An imbalance in these ratios in vivo may underlie diseases of immunologic origin, e.g., autoimmunity. 相似文献
127.
128.
B.?S.?HanssonEmail author M.?A.?Carlsson B.?Kalinovà 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2003,189(4):301-308
The sphinx moth Manduca sexta is a well-studied insect with regard to central olfactory functions. Until now, the innervation patterns of olfactory receptor neurons into the array of olfactory glomeruli in the antennal lobe have, however, been unclear. Using optical imaging to visualize calcium dynamics within the antennal lobe we demonstrate specific patterns elicited by sex pheromone components and plant-derived odours. These patterns mainly reflect receptor neuron activity. Within the male-specific macroglomerular complex the two major pheromone components evoke stereotyped activity in either of two macroglomerular complex glomeruli. Based on previous knowledge of output neuron specificity, our results suggest a matching of information between input and output in the macroglomerular complex. Plant odours evoked activity in the sexually isomorphic glomeruli. Two major results were obtained: (1). terpenes and aromatic compounds activate different clusters of glomeruli with only minor overlapping, and (2). the position of certain key glomeruli is fixed in both males and females, which suggests that host-plant related odorants are processed in a similar way in both sexes. 相似文献
129.
Fukuda A Fukuda H Jönsson M Swanpalmer J Hertzman S Lannering B Björk-Eriksson T Màrky I Blomgren K 《Journal of neurochemistry》2005,94(6):1604-1619
Ionizing radiation induced acute cell death in the dentate gyrus subgranular zone (SGZ) and the subventricular zone (SVZ). Hypomyelination was also observed. The effects of mild hypothermia and hyperthermia for 4 h after irradiation (IR) were studied in postnatal day 9 rats. One hemisphere was irradiated with a single dose of 8 Gy and animals were randomized to normothermia (rectal temperature 36 degrees C for 4 h), hypothermia (32 degrees C for 4 h) or hyperthermia (39 degrees C for 4 h). Cellular injury, e.g. chromatin condensation and nitrotyrosine formation, appeared to proceed faster when the body temperature was higher. Caspase-3 activation was more pronounced in the hyperthermia group and nuclear translocation of p53 was less pronounced in the hypothermia group 6 h after IR. In the SVZ the loss of nestin-positive progenitors was more pronounced (48%) and the size was smaller (45%) in the hyperthermia group 7 days post-IR. Myelination was not different after hypo- or hyperthermia. This is the first report to demonstrate that hypothermia may be beneficial and that hyperthermia may aggravate the adverse side-effects after radiation therapy to the developing brain. 相似文献
130.
E Villa R Vukotic C Cammà S Petta A Di Leo S Gitto E Turola A Karampatou L Losi V Bernabucci A Cenci S Tagliavini E Baraldi N De Maria R Gelmini E Bertolini M Rendina A Francavilla 《PloS one》2012,7(9):e44624