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puma rs 0

 
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Bernie Esther
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Dołączył: 21 Maj 2020
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PostWysłany: Czw Maj 21, 2020 04:45    Temat postu: puma rs 0 Odpowiedz z cytatem

Our data also provide a rationale for a novel GBM therapy, puma sneakers in which both the kinase-dependent and -independent activities of EGFR/EGFRvIII are targeted simultaneously in order to improve EGFR-based mono and combinational therapies.The results in this study showing GBMs, known to be highly resistant to therapy, to express high levels of the proapoptotic protein, PUMA, is paradoxical. To gain insight into this paradox, we investigated EGFR and EGFRvIII, frequently over-expressed in GBM similar to PUMA, and found both pathways to be inversely linked to the apoptotic response of GBM cells. These results allow the speculation that a subset of GBMs (34%) is capable of up-regulating EGFR/EGFRvIII expression in order to negatively regulate PUMA and thereby, escape therapy-induced apoptosis. Our results, however, also indicate that PUMA can be negatively regulated by EGFR/EGFRvIII-independent mechanisms, given the fact ( Fig. 2a ) that a portion of PUMA-expressing GBMs do not express EGFR/EGFRvIII.

EGFR has been shown to interact with and stabilize sodium/glucose cotransporter 1, leading to maintenance of intracellular glucose level and prevention of autophagic cell death [ 50 ], and to bind to and phosphorylate the human GSTP1 protein [ 51 ]. Interestingly, the tumor suppressor, p53, has been shown to translocate onto the mitochondria and bind to anti-apoptotic Bcl-xL, leading to apoptosis [ puma schoenen 52 ]. Similarly, ErbB4 undergoes mitochondrial translocalization and subsequently interacts with the anti-apoptotic Bcl-2, leading to apoptosis [ 25 ]. Unlike p53 and ErbB4, EGFR and EGFRvIII interact with proapoptotic PUMA to antagonize mitochondrial transport of PUMA, leading to reduced levels of apoptosis and increased cell survival. Together, these findings describe a new class of protein-protein interactions that occurs between Bcl-2 and non-Bcl-2 proteins, and that these interactions regulate intrinsic mitochondria-mediated puma rs x apoptosis.

Our results showed that Iressa, an EGFR-targeted tyrosine kinase inhibitor, fails to disrupt the interaction between EGFR/EGFRvIII and PUMA, suggesting that this kinase-independent anti-apoptotic activity may be an important mechanism underlying the limited clinical efficacy demonstrated by EGFR-targeted therapy. These observations also suggest that a higher therapeutic efficacy may be achieved by targeting both kinase-dependent and -independent functions of EGFR. In support of this premise, our data showed that mimicking PUMA's proapoptotic activity using a Bcl-2/Bcl-xL inhibitor sensitized both EGFR- and EGFRvIII-expressing GBM cells to Iressa and that most GBM cell lines we analyzed expressed high levels of Bcl-2 and Bcl-xL. Collectively, these findings provide strong evidence for a novel mechanism by which EGFR confers GBM resistance to EGFR-targeted therapy and potentially other therapies, as well as, provide a rationale for a novel combinational anti-GBM therapy that target both EGFR and puma thunder intrinsic apoptotic pathways.

Camera trapping has advantages over radiotelemetry in its potential to provide data on the complete array of individuals within the study area. The 23 individually identified male jaguars showed high levels of overlap in ranges, with up to 5 different males captured at the same location in the same month. Low levels of avoidance between individuals and a high flux of individuals contributed to low consistency in home-range ownership over the long term (3 months to 2 years). Jaguars and pumas had similar nocturnal activity schedules. Both species used similar habitats within the Cockscomb Basin, indicated by a high correlation in capture rates per location between species. Apart from their overall spatial similarities, jaguars and pumas avoided using the same location at the same time. This interspecific segregation was detectable over and above the spatial and temporal segregation of individual jaguars.

Registramos baja consistencia en las áreas de actividad ("home ranges") en períodos de 3 meses a dos años, con bajos niveles de separación espacial entre individuos pero con un alto flujo de individuos. Los patrones de actividad nocturna de jaguares y pumas fueron similares. Ambas especies usaron hábitats similares en la cuenca del Cockscomb, indicado por una alta correlación en las tasas de captura por sitio entre las especies. A pesar de estos patrones, los jaguares y pumas evitaron usar el mismo sitio al mismo tiempo. Esta segregación interespecífica fue detectada sobre la segregación espacial y temporal de los individuos de jaguar.In the present study we employ this longer ND5 segment to investigate the evolutionary history of P. concolor , with emphasis on South American populations, which were previously found to harbor high levels of diversity and inferred to have played a key role in the historical demography of this species ( Culver et al. , 2000 ).

Given that the geographic sampling of South American pumas was limited in that first study, we aimed here to expand the representation of the puma rs 0 various regions of this sub-continent, so as to allow refined inferences of population structure, maternal gene flow and demographic history. In addition to expanding the geographic coverage of South American regions to refine inferences on patterns of matrilineal subdivision, we have performed novel analyses on puma demographic history, which revealed consistent evidence of a recent population expansion in South America, prior to re-colonization of North America.We obtained blood and tissue samples from 77 pumas including wild individuals captured during field-ecology projects, caught by farmers or road-killed, as well as captive [img]http://www.bargansa.com/images/red/puma rs 0-174ykt.jpg[/img] animals with known geographic origin ( Table S1 ).
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Wysłany: Czw Maj 21, 2020 04:45    Temat postu:

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