1,720,981 research outputs found

    Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

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    Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors

    Molecular control of neuromuscular junction development

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    Skeletal muscle innervation is a multi-step process leading to the neuromuscular junction (NMJ) apparatus formation. The transmission of the signal from nerve to muscle occurs at the NMJ level. The molecular mechanism that orchestrates the organization and functioning of synapses is highly complex, and it has not been completely elucidated so far. Neuromuscular junctions are assembled on the muscle fibers at very precise locations called end plates (EP). Acetylcholine receptor (AChR) clusterization at the end plates is required for an accurate synaptic transmission. This review will focus on some mechanisms responsible for accomplishing the correct distribution of AChRs at the synapses. Recent evidences support the concept that a dual transcriptional control of AChR genes in subsynaptic and extrasynaptic nuclei is crucial for AChR clusterization. Moreover, new players have been discovered in the agrin-MuSK pathway, the master organizer of postsynaptical differentiation. Mutations in this pathway cause neuromuscular congenital disorders. Alterations of the postynaptic apparatus are also present in physiological conditions characterized by skeletal muscle wasting. Indeed, recent evidences demonstrate how NMJ misfunctioning has a crucial role at the onset of age-associated sarcopenia

    Genetic instability of heterochromatin following transposition of the Line-like I factor in Drosophila melanogaster.

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    In the present work, we have asked whether a group of 13 essential genes mapping to the heterochromatin of Drosophila melanogaster chromosome 2 are mutable following transposition of the I factor during I-R hybrid dysgenesis. We found that the frequency of lethal events mapping to chromosome 2 heterochromatin is surprisingly high, despite the low density of genetic functions identified in this region compared with euchromatin. Cytogenetic and molecular analyses indicated that the recovered mutations correspond either to insertions or to rearrangements. Moreover, chromosomes bearing specific heterochromatic lethal mutations were generated by recombination in the heterochromatin. Together, these data indicate that I factors transpose with high frequency into pericentric regions of chromosome 2 and may play a role in the evolution of constitutive heterochromatin

    Genetic instability of heterochromatin following transposition of the Line-like I factor in Drosophila melanogaster.

    No full text
    In the present work, we have asked whether a group of 13 essential genes mapping to the heterochromatin of Drosophila melanogaster chromosome 2 are mutable following transposition of the I factor during I-R hybrid dysgenesis. We found that the frequency of lethal events mapping to chromosome 2 heterochromatin is surprisingly high, despite the low density of genetic functions identified in this region compared with euchromatin. Cytogenetic and molecular analyses indicated that the recovered mutations correspond either to insertions or to rearrangements. Moreover, chromosomes bearing specific heterochromatic lethal mutations were generated by recombination in the heterochromatin. Together, these data indicate that I factors transpose with high frequency into pericentric regions of chromosome 2 and may play a role in the evolution of constitutive heterochromatin

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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