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101.
Heloisa P. Soares Yang Ni Krisztina Kisfalvi James Sinnett-Smith Enrique Rozengurt 《PloS one》2013,8(2)
The mTOR pathway is aberrantly stimulated in many cancer cells, including pancreatic ductal adenocarcinoma (PDAC), and thus it is a potential target for therapy. However, the mTORC1/S6K axis also mediates negative feedback loops that attenuate signaling via insulin/IGF receptor and other tyrosine kinase receptors. Suppression of these feed-back loops unleashes over-activation of upstream pathways that potentially counterbalance the antiproliferative effects of mTOR inhibitors. Here, we demonstrate that treatment of PANC-1 or MiaPaCa-2 pancreatic cancer cells with either rapamycin or active-site mTOR inhibitors suppressed S6K and S6 phosphorylation induced by insulin and the GPCR agonist neurotensin. Rapamycin caused a striking increase in Akt phosphorylation at Ser473 while the active-site inhibitors of mTOR (KU63794 and PP242) completely abrogated Akt phosphorylation at this site. Conversely, active-site inhibitors of mTOR cause a marked increase in ERK activation whereas rapamycin did not have any stimulatory effect on ERK activation. The results imply that first and second generation of mTOR inhibitors promote over-activation of different pro-oncogenic pathways in PDAC cells, suggesting that suppression of feed-back loops should be a major consideration in the use of these inhibitors for PDAC therapy. In contrast, metformin abolished mTORC1 activation without over-stimulating Akt phosphorylation on Ser473 and prevented mitogen-stimulated ERK activation in PDAC cells. Metformin induced a more pronounced inhibition of proliferation than either KU63794 or rapamycin while, the active-site mTOR inhibitor was more effective than rapamycin. Thus, the effects of metformin on Akt and ERK activation are strikingly different from allosteric or active-site mTOR inhibitors in PDAC cells, though all these agents potently inhibited the mTORC1/S6K axis. 相似文献
102.
Isabel Roncero Elvira Alvarez Carlos Acosta Carmen Sanz Pedro Barrio Veronica Hurtado-Carneiro Deborah Burks Enrique Blázquez 《PloS one》2013,8(4)
Insulin receptor substrate (IRS) proteins play important roles in hepatic nutrient homeostasis. Since glucokinase (GK) and glucokinase regulatory protein (GKRP) function as key glucose sensors, we have investigated the expression of GK and GKRP in liver of Irs-2 deficient mice and Irs2(−/−) mice where Irs2 was reintroduced specifically into pancreatic β-cells [RIP-Irs-2/IRS-2(−/−)]. We observed that liver GK activity was significantly lower (p<0.0001) in IRS-2(−/−) mice. However, in RIP-Irs-2/IRS-2(−/−) mice, GK activity was similar to the values observed in wild-type animals. GK activity in hypothalamus was not altered in IRS-2(−/−) mice. GK and GKRP mRNA levels in liver of IRS-2(−/−) were significantly lower, whereas in RIP-Irs-2/IRS-2(−/−) mice, both GK and GKRP mRNAs levels were comparable to wild-type animals. At the protein level, the liver content of GK was reduced in IRS-2(−/−) mice as compared with controls, although GKRP levels were similar between these experimental models. Both GK and GKRP levels were lower in RIP-Irs-2/IRS-2(−/−) mice. These results suggest that IRS-2 signalling is important for maintaining the activity of liver GK. Moreover, the differences between liver and brain GK may be explained by the fact that expression of hepatic, but not brain, GK is controlled by insulin. GK activity was restored by the β-cell compensation in the RIP-Irs-2/IRS-2 mice. Interestingly, GK and GKRP protein expression remained low in RIP-Irs-2/IRS-2(−/−) mice, perhaps reflecting different mRNA half-lives or alterations in the process of translation and post-translational regulation. 相似文献
103.
At the individual level, to be behaviourally lateralized avoids costly duplication of neural circuitry and decreases possible contradictory order from the two brain hemispheres. However, being prey behaviour lateralized at higher hierarchical levels could generate different negative implications, especially if predators are able to make predictions after multiple encounters. These conflicting pressures, namely between the advantages for individuals and the disadvantages for populations could be concealed if higher-level lateralization would arise from the combination of lateralized behaviours of individuals which are mutually dependent. Here, we investigated the lateralization patterns in the escape behaviour of the gecko Tarentola angustimentalis undergoing a predatory attack simulation in a “T” maze experiment. Results showed that gecko populations displayed different degrees of lateralization, with an overall dominance of right-biased individuals. This trend is similar to that observed in the Podarcis wall lizards, which share predators with Tarentola. In addition, different morphological parameters plausible to affect refuge selection were explored in order to link directional asymmetries at morphological level with lateralization during refuge selection. 相似文献
104.
Alvarado Claudia Ramírez Jose Martín Herrera-López Enrique J. Cortez-Valladolid Diego Ramírez Gerardo 《Biological trace element research》2020,193(1):226-233
Biological Trace Element Research - Fluoride accumulates and is toxic to bones. Clinical bone lesions occur in a phased manner, being less severe early in the natural course of skeletal fluorosis.... 相似文献
105.
Danelia Ramírez-Ramírez Monica L. Salgado-Lucio Ana L. Roa-Espitia Reyna Fierro Humberto González-Márquez Joaquín Cordero-Martínez Enrique O. Hernández-González 《Journal of cellular biochemistry》2020,121(4):2864-2876
Actin cytoskeleton remodeling is a critical process for the acquisition of fertilizing capacity by spermatozoa during capacitation. However, the molecular mechanism that regulates this process has not been fully elucidated. In somatic cells, Ras-related C3 botulinum toxin substrate 1 protein (Rac1) promotes the polymerization of actin by participating in the modeling of two structures: lamellipodia and adhesion complexes linked with the plasma membrane. Rac1 is expressed in mammalian spermatozoa; however, the role of Rac1 in sperm physiology is unknown. This study aimed to elucidate the participation of Rac1 in capacitation and acrosome reaction (AR). Rac1 was found to be dispersed throughout the acrosome and without changes in the middle piece. After 60 minutes of capacitation, Rac1 was found in the apical region of the acrosome only, which concurred with an increase in Rac1-GTP. Rac1 inhibition prevented such changes. In the middle piece, Rac1 localization remained unchanged. Besides, Rac1 inhibition blocked capacitation and AR. The present study demonstrates that Rac1 participates only in the actin cytoskeleton remodeling that occurs in the acrosomal apical region during capacitation, a region where a large amount of actin is polymerized and shaped in a diadem-like structure. Our data also show that this actin cytoskeleton organized by Rac1 interacts with filamin-1, and such interaction was blocked by the inhibition of Rac1, which led to a different organization of the actin cytoskeleton. All these outcomes imply that the formation of an F-actin cytoskeleton in the acrosomal apical region is a necessary event for capacitation and AR, and which is Rac1 driven. 相似文献
106.
Ayelen Tschopp Franco Cristiani Nestor Aníbal García Enrique Alberto Crespo Mariano Alberto Coscarella 《Journal of fish biology》2020,97(3):656-667
Overexploitation of marine communities can lead to modifications in the structure of the food web and can force organisms like elasmobranchs to change their feeding habits. To evaluate the impact that fisheries have on food webs and on the interactions between species, it is necessary to describe and quantify the diet of the species involved and follow it through time. This study compares the diet of five skate species using the data obtained from the by-catch of the Argentine hake (Merluccius hubbsi) fishery in north and central Patagonia, Argentina. Diet composition was assessed by analysing the digestive tract contents and trophic overlapping between species of the genus Bathyraja: Bathyraja albomaculata, Bathyraja brachyurops, Bathyraja macloviana, Bathyraja magellanica and Bathyraja multispinis. A total of 184 stomachs were analysed. The diets of B. albomaculata and B. macloviana mainly comprised annelids, whereas that of B. brachyurops primarily comprised fish, including hake heads discarded by the fishery. The diets of B. magellanica and B. multispinis were largely based on crustaceans. Despite the morphological similarities and their shared preference for benthic habitats, no complete diet overlaps were found between the different species. These results suggest that these skate species have undergone a process of diet specialisation. This is a common feeding strategy that occurs to successfully eliminate competition when resources are limited, which corresponds to the conditions found in an environment being affected by the pressures of overfishing. 相似文献
107.
Javier Hernán Rojo Daniel Alfredo Fernández Daniel Enrique Figueroa Claudia Clementina Boy 《Journal of fish biology》2020,96(4):956-967
This study reports the phenotypic and genetic differences between individuals of puyen Galaxias maculatus from two sites in the same river basin in Tierra del Fuego National Park, southern South America. Individuals from the two sampling sites presented morphometric and genetic differences. The morphometric differences indicated that individuals from Laguna Negra (LN) were short and more robust and had large eyes, whereas those from Arroyo Negro (AN) were thin and elongated and had small eyes. Genetic differences showed that AN individuals had a greater genetic structuration and an older demographic history than LN individuals. The results of this study affirmed that the individuals from the two sampling sites belong to different populations with a high degree of isolation. The demographic history could indicate that the individuals of G. maculatus which migrated to northern areas during the last glaciation settled in the Beagle Channel after its formation. The LN population could have originated after the retreat of the glaciers, migrating from AN. 相似文献
108.
Mariana Degrati Silvana L. Dans Griselda V. Garaffo Ariel G. Cabreira Federico Castro Machado Enrique A. Crespo 《Marine Mammal Science》2013,29(4):691-704
The aim of this work was to analyze the sequential foraging behavior of dusky dolphins (Lagenorhynchus obscurus). Foraging sequences were defined when more than two feeding bouts occur with a traveling bout between them. We hypothesized that traveling costs of searching for prey patches were related to the time spent feeding on a patch. In addition, the distribution and seasonal variation of anchovy schools were studied in the area to better understand dolphins' behavior. We observed dolphins from a research vessel from 2001 to 2007, and recorded their location and behavior. Anchovy data were collected during two hydro‐acoustic surveys. Dusky dolphin behaviors varied seasonally; they spent a greater proportion of time traveling and feeding in the warm season (Kruskal‐Wallis: H = 172.07, P < 0.01). During the cold season dolphin groups were more likely to exhibit diving behavior and less surface feeding. We found a positive correlation between searching and foraging time (r = 0.88, P = 0.019), suggesting that the costs associated with searching were compensated by an increase in the energy intake during the foraging bout. There was an association between dusky dolphin and anchovy distribution, in that they co‐varied spatially and seasonally. 相似文献
109.
Mercedes di Pasquo George W. Grader Peter Isaacson Paulo A. Souza Roberto Iannuzzi Enrique Díaz-Martínez 《Historical Biology》2013,25(7):868-897
This paper presents new data about Early Permian (Cisuralian) strata, palynostratigraphy and absolute dating from the Copacabana Formation in central Bolivia. Recent stratigraphic and palynologic data from marine and transitional rocks at Apillapampa refine the age of Cisuralian palynomorphs in South America. Twelve samples interbedded with five volcanic ashes (processed and productive) yielded 94 palynomorph species arranged in two informal palynoassemblages: the lower assemblage Vittatina costabilis corresponds to one sample near the base of the Copacabana Formation and the upper Lueckisporites virkkiae assemblage occurs in overlying marine and coal-bearing transitional intervals. Ages were also independently refined by a modern review of conodonts, fusulinids, along with those U–Pb radiometric ages (Isotope Dilution Thermal Ionization Mass Spectrometry [ID-TIMS] of zircon-bearing interbedded tuffs). These data suggest that the lower marine member of the Copacabana Formation at this location is Asselian and Sakmarian. Lueckisporites virkkiae is a key species of palynomorph utilised in South American and global Permian biostratigraphic reconstructions. Hence, a thorough global comparison of these palynofloras and correlations is addressed in this contribution, considering first appearances of mainly cosmopolitan diagnostic taxa. Correlations are established with many similar Permian palynofloras, some also constrained with radiometric data, in South America (Brazil, Uruguay and Argentina) and elsewhere. 相似文献
110.
In an industrial seawater cooling system, the effects of three different antifouling treatments, viz. sodium hypochlorite (NaClO), aliphatic amines (Mexel®432) and UV radiation, on the characteristics of the fouling formed were evaluated. For this study a portable pilot plant, as a side-stream monitoring system and seawater cooling system, was employed. The pilot plant simulated a power plant steam condenser, having four titanium tubes under different treatment patterns, where fouling progression could be monitored. The nature of the fouling obtained was chiefly inorganic, showing a clear dependence on the antifouling treatment employed. After 72 days the tubes under treatment showed a reduction in the heat transfer resistance (R) of around 70% for NaClO, 48% for aliphatic amines and 55% for UV, with respect to the untreated tube. The use of a logistic model was very useful for predicting the fouling progression and the maximum asymptotic value of the increment in the heat transfer resistance (ΔR max). The apparent thermal conductivity (λ) of the fouling layer showed a direct relationship with the percentage of organic matter in the collected fouling. The characteristics and mode of action of the different treatments used led to fouling with diverse physicochemical properties. 相似文献