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61.
Braun T Carvalho G Grosjean J Ades L Fabre C Boehrer S Debili N Fenaux P Kroemer G 《Apoptosis : an international journal on programmed cell death》2007,12(6):1101-1108
Myelodysplastic syndromes (MDS) constitute a preneoplastic condition in which potentially malignant cancer stem cells continuously
die during differentiation. This MDS-associated cell death often involves caspase-3 activation, yet can also occur without
caspase activation, for instance in differentiating megakaryocytes (MK). We investigated, the mechanisms through which MK
from MDS patients undergo premature cell death. While polyploid, mature MK from healthy subjects or MDS patients manifested
caspase-3 activation during terminal differentiation, freshly isolated, immature MK from MDS died without caspase-3 activation.
Similarly, purified bone marrow CD34+ cells from MDS patients that were driven into MK differentiation in vitro died without caspase-3 activation at an immature stage, before polyploidization. The premature death of MDS MK was accompanied
by the mitochondrial release of cytochrome c, Smac/DIABLO and endonuclease G, a caspase-independent death effector, as well loss of the mitochondrial membrane potential
and plasma membrane phosphatidylserine exposure before definitive loss of viability. Thus, a stereotyped pattern of mitochondrial
alterations accompanies differentiation-associated MK death in MDS.
T. Braun and G. Carvalho contributed equally to this paper. 相似文献
62.
Redox signaling has emerged as a unifying theme in many seemingly disparate disciplines. Such signaling has been widely studied in bacteria and eukaryotic organelles and is often mediated by reactive oxygen species (ROS). In this context, reduced glutathione (GSH) acts as an important intracellular antioxidant, diminishing ROS and potentially affecting redox signaling. Complementing this cell-level perspective, colonial hydroids can be a useful model for understanding organism-level redox signaling. These simple, early-evolving animals consist of feeding polyps connected by tubelike stolons. Colonies treated exogenously with GSH or reduced glutathione ethyl ester (GEE) were expected to show a morphological change to sheetlike growth typical of low levels of ROS. Contrary to expectations, diminished stolon branching and polyp initiation was observed. Such runnerlike growth is associated with higher levels of ROS, and surprisingly, such higher levels were found in GSH- and GEE-treated colonies. Further investigations show that GSH triggered a feeding response in hydroid polyps, increasing oxygen uptake but at the same time relaxing mitochondrion-rich contractile regions at the base of polyps. Diminished gastrovascular flow and increased emissions of mitochondrial ROS also correlated with the observed runnerlike growth. In contrast to cell-level, "bottom-up" views of redox signaling, here the phenotype may arise from a "top-down" interaction of mitochondrion-rich regions and organism-level physiology. Such multicellular redox regulation may commonly occur in other animals as well. 相似文献
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Charles-André Couture Stéphane Bancelin Jarno Van?der?Kolk Konstantin Popov Maxime Rivard Katherine Légaré Gabrielle Martel Hélène Richard Cameron Brown Sheila Laverty Lora Ramunno Fran?ois Légaré 《Biophysical journal》2015,109(12):2501-2510
In this work, we report the implementation of interferometric second harmonic generation (SHG) microscopy with femtosecond pulses. As a proof of concept, we imaged the phase distribution of SHG signal from the complex collagen architecture of juvenile equine growth cartilage. The results are analyzed in respect to numerical simulations to extract the relative orientation of collagen fibrils within the tissue. Our results reveal large domains of constant phase together with regions of quasi-random phase, which are correlated to respectively high- and low-intensity regions in the standard SHG images. A comparison with polarization-resolved SHG highlights the crucial role of relative fibril polarity in determining the SHG signal intensity. Indeed, it appears that even a well-organized noncentrosymmetric structure emits low SHG signal intensity if it has no predominant local polarity. This work illustrates how the complex architecture of noncentrosymmetric scatterers at the nanoscale governs the coherent building of SHG signal within the focal volume and is a key advance toward a complete understanding of the structural origin of SHG signals from tissues. 相似文献
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During brain development, each neuron must find and synapse with the correct pre- and postsynaptic partners. The complexity
of these connections and the relatively large distances some neurons must send their axons to find the correct partners makes
studying brain development one of the most challenging, and yet fascinating disciplines in biology. Furthermore, once the
initial connections have been made, the neurons constantly remodel their dendritic and axonal arbours in response to changing
demands. Neurexin and neuroligin are two cell adhesion molecules identified as important regulators of this process. The importance
of these genes in the development and modulation of synaptic connectivity is emphasised by the observation that mutations
in these genes in humans have been associated with cognitive disorders such as Autism spectrum disorders, Tourette syndrome
and Schizophrenia. The present review will discuss recent advances in our understanding of the role of these genes in synaptic
development and modulation, and in particular, we will focus on recent work in invertebrate models, and how these results
relate to studies in mammals. 相似文献
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N-glycans are post-translational modifications in which the sugar chain is covalently linked to protein by a GlcNAcβ1-N-asparagine linkage. Drosophila melanogaster and other invertebrates, but not vertebrates, synthesize large amounts of "paucimannose" N-glycans that contain only three or four mannose residues. The enzyme UDP-GlcNAc:α3-D-mannoside β1,2-N-acetylglucosaminyltransferase I (GnTI, encoded by the Mgat1 gene) controls the synthesis of paucimannose N-glycans. Either deletion or neuron-specific knockdown of Mgat1 in wild type flies results in pronounced defects in locomotion, structural defects in the adult central nervous system and a severely reduced lifespan. We have recently shown that neuronal expression of a wild-type Mgat1 transgene in Mgat1-null flies rescues the structural defects in the brain (fused β-lobes) and the shortened lifespan and, surprisingly, results in a dramatic 135% increase in mean lifespan relative to genetically identical controls that do not express the transgene. In this review, we discuss various approaches that can be used to determine the roles of paucimannose N-glycans in Drosophila longevity and in the adult CNS. 相似文献
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