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571.
Uri Hanania Margarita Velcheva Nachman Sahar Moshe Flaishman Etti Or Oded Degani Avihai Perl 《Plant cell reports》2009,28(7):1033-1042
572.
Anna Bakhrat Tracy Pritchett Gabriella Peretz Kimberly McCall Uri Abdu 《Apoptosis : an international journal on programmed cell death》2010,15(12):1425-1434
In Drosophila, the checkpoint protein-2 kinase (DmChk2) and its downstream effector protein, Dmp53, are required for DNA damage-mediated
cell cycle arrest, DNA repair and apoptosis. In this study we focus on understanding the function of these two apoptosis inducing
factors during ovarian development. We found that expression of Dmp53, but not DmChk2, led to loss of ovarian stem cells.
We demonstrate that expression of DmChk2, but not Dmp53, induced mid-oogenesis cell death. DmChk2 induced cell death was not
suppressed by Dmp53 mutant, revealing for the first time that in Drosophila, over-expression of DmChk2 can induce cell death which is independent of Dmp53. We found that over-expression of caspase
inhibitors such as DIAP1, p35 and p49 did not suppress DmChk2- and Dmp53-induced cell death. Thus, our study reveals stage-specific
effects of Dmp53 and DmChk2 in oogenesis. Moreover, our results demonstrate that although DmChk2 and Dmp53 affect different
stages of ovarian development, loss of ovarian stem cells by p53 expression and mid-oogenesis cell death induced by DmChk2
do not require caspase activity. 相似文献
573.
Background
The question of whether intact somatic cells committed to a specific differentiation fate, can be reprogrammed in vivo by exposing them to a different host microenvironment is a matter of controversy. Many reports on transdifferentiation could be explained by fusion with host cells or reflect intrinsic heterogeneity of the donor cell population.Methodology/Principal Findings
We have tested the capacity of cloned populations of mouse and human muscle progenitor cells, committed to the myogenic pathway, to transdifferentiate to neurons, following their inoculation into the developing brain of newborn mice. Both cell types migrated into various brain regions, and a fraction of them gained a neuronal morphology and expressed neuronal or glial markers. Likewise, inoculated cloned human myogenic cells expressed a human specific neurofilament protein. Brain injected donor cells that expressed a YFP transgene controlled by a neuronal specific promoter, were isolated by FACS. The isolated cells had a wild-type diploid DNA content.Conclusions
These and other results indicate a genuine transdifferentiation phenomenon induced by the host brain microenvironment and not by fusion with host cells. The results may potentially be relevant to the prospect of autologous cell therapy approach for CNS diseases. 相似文献574.
Veronique Guillemard Ljubica Ivanisevic Alba Galan Garcia Vicki Scholten Oscar M. Lazo Francisca C. Bronfman H. Uri Saragovi 《Developmental neurobiology》2010,70(3):150-164
The D5 domain of TrkC receptors is a docking site for Neurotrophin‐3 (NT‐3), but other domains may be relevant for function or harmonizing signals with p75NTR coreceptors. We report a monoclonal antibody (mAb) 2B7 targeting the juxtamembrane domain of TrkC. mAb 2B7 binds to murine and human TrkC receptors and is a functional agonist that affords activation of TrkC, AKT, and MAPK. These signals result in cell survival but not in cellular differentiation. Monomeric 2B7 Fabs also affords cell survival. Binding of 2B7 mAb and 2B7 Fabs to TrkC are blocked by NT‐3 in a dose‐dependent manner but not by pro‐NT‐3. Expression of p75NTR coreceptors on the cell surface block the binding and function of mAb 2B7, whereas NT‐3 binding and function are enhanced. mAb 2B7 defines a previously unknown neurotrophin receptor functional hot spot; that exclusively generates survival signals; that can be activated by non‐dimeric ligands; and potentially unmasks a site for p75‐TrkC interactions. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2010. 相似文献
575.
Ashery U Yizhar O Rotblat B Elad-Sfadia G Barkan B Haklai R Kloog Y 《Cellular and molecular neurobiology》2006,26(4-6):469-493
Summary 1. Ras signaling and oncogenesis depend on the dynamic interplay of Ras with distinctive plasma membrane (PM) microdomains and various intracellular compartments. Such interaction is dictated by individual elements in the carboxy-terminal domain of the Ras proteins, including a farnesyl isoprenoid group, sequences in the hypervariable region (hvr)-linker, and palmitoyl groups in H/N-Ras isoforms.2. The farnesyl group acts as a specific recognition unit that interacts with prenyl-binding pockets in galectin-1 (Gal-1), galectin-3 (Gal-3), and cGMP phosphodiesterase δ. This interaction appears to contribute to the prolongation of Ras signals in the PM, the determination of Ras effector usage, and perhaps also the transport of cytoplasmic Ras. Gal-1 promotes H-Ras signaling to Raf at the expense of phosphoinositide 3-kinase (PI3-K) and Ral guanine nucleotide exchange factor (RalGEF), while galectin-3 promotes K-Ras signaling to both Raf and PI3-K.3. The hvr-linker and the palmitates of H-Ras and N-Ras determine the micro- and macro-localizations of these proteins in the PM and in the Golgi, as well as in ‘rasosomes’, randomly moving nanoparticles that carry palmitoylated Ras proteins and their signal through the cytoplasm.4. The dynamic compartmentalization of Ras proteins contributes to the spatial organization of Ras signaling, promotes redistribution of Ras, and provides an additional level of selectivity to the signal output of this regulatory GTPase. 相似文献
576.
The immune system plays a major role in the protection against cancer. Identifying and characterizing the pathways mediating this immune surveillance are thus critical for understanding how cancer cells are recognized and eliminated. Aneuploidy is a hallmark of cancer, and we previously found that untransformed cells that had undergone senescence due to highly abnormal karyotypes are eliminated by natural killer (NK) cells in vitro. However, the mechanisms underlying this process remained elusive. Here, using an in vitro NK cell killing system, we show that non‐cell‐autonomous mechanisms in aneuploid cells predominantly mediate their clearance by NK cells. Our data indicate that in untransformed aneuploid cells, NF‐κB signaling upregulation is central to elicit this immune response. Inactivating NF‐κB abolishes NK cell‐mediated clearance of untransformed aneuploid cells. In cancer cell lines, NF‐κB upregulation also correlates with the degree of aneuploidy. However, such upregulation in cancer cells is not sufficient to trigger NK cell‐mediated clearance, suggesting that additional mechanisms might be at play during cancer evolution to counteract NF‐κB‐mediated immunogenicity. 相似文献
577.
Uri Liberman 《Journal of mathematical biology》1984,21(1):1-10
The count-location (C-L) chiasma formation schemes introduced by Karlin and Liberman (1979b) encompass a broad class of map functions involving positive, negative or no chiasma interference. The C-L schemes do not explictly assume a specific mechanism of crossover formation, but rather a statistical property of the process. If viewed as a stochastic point process along the chromosome, it is shown that a crossing over mechanism having the C-L property is actually a rescaled mixture of Poisson processes. Surprisingly it turns out that these C-L point processes involve negative interference throughout the entire genome.Research supported in part by NIH grants GM 28016 and GM 10452 相似文献
578.
A model in which selection is mediated by differential fertilities among the genotypes at two diallelic loci is proposed. Fertility depends only on the number of heterozygous loci participating in the mating. Classes analogous to symmetric equilibria in symmetric viability models are determined explicitly and shown to exhibit stability behavior very different from the viability results. Linkage equilibrium is shown to occur in a relatively asymmetric fashion and to overlap in stability with linkage disequilibrium. In many cases single-locus or two-locus polymorphism is shown to be stable simultaneously with chromosome fixation even under very tight linkage. It is suggested that historical effects may be of great significance in the evolution of systems in which fertility is the primary agent of natural selection. 相似文献
579.
Galila Agam Rivka Luria Orit Shohat Alexander Dvilansky Uri Seligsohn Avinoam Livne 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1985,847(3):293-300
Platelet surface glycoproteins IIb-IIIa are considered to function as the binding site for fibrinogen. Fibrinogen binding is essential for platelet aggregation and several amines have been shown to inhibit this binding. The present study compares the binding properties of 125I-fibrinogen and [3H]lysine with platelets activated by the Ca2+ ionophore A23187. Many lines of similarities in the binding properties are apparent; however, several differences were also found. The similarities are listed below and the differences are pointed out in parentheses. (a) Marked enhancement by platelet activation; (b) deficiency of binding by thrombasthenic platelets lacking the glycoproteins IIb-IIIa; (c) saturability (fibrinogen binding approaches saturation at more than 12 μM, within 10 min; lysine binding at more than 100 mM within 1 min); (d) Ca2+-dependence (at 1 mM Ca2+ lysine binding is minute and fibrinogen binding is half-saturated); (e) reversibility; the binding achieved within 10 min is exchangeable; dissociation depends upon time and external ligand concentration; (f) inhibition by the oligoamines His-Lys and Lys4; (g) inhibition by serum from a thrombasthenic patient who developed anti-glycoproteins IIb-IIIa antibodies; (h) specificity; alanine neither binds to activated platelets nor inhibits fibrinogen binding; it thus appears that the lysine which associates with activated platelets is mostly bound onto the surface of the cells rather than being incorporated; Moreover, the major site of lysine binding seems to be the complexed glycoproteins IIb-IIIa. 相似文献
580.
Summary The paper develops conditions for the existence and the stability of central equilibria emanating from selection recombination interaction with generalized nonepistatic selection forms operating in multilocus multiallele systems. The selection structure admits a natural representation as simple sums of Kronecker products based on a common set of marginal selection components. A flexible parametrization of the recombination process is introduced leading to a canonical derivation of the transformation equations connecting gamete frequency states over successive generations. Conditions for the existence and stability of multilocus Hardy-Weinberg (H.W.) type equilibria are elaborated for the classical nonepistatic models (multiplicative and additive viability effects across loci) as well as for generalized nonepistatic selection expressions. It is established that the range of recombination distributions maintaining a stable H.W. polymorphic equilibrium is confined to loose linkage in the pure multiplicative case, but is not restricted in the additive model. In the bisexual case we ascertain for the generalized nonepistatic model the stability conditions of a common H.W. polymorphism.This paper was supported in part by NIH Grant GM 10452-14 and NSF Grant MCS 75-23608. 相似文献