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181.
Gärtner A Fornasiero EF Munck S Vennekens K Seuntjens E Huttner WB Valtorta F Dotti CG 《The EMBO journal》2012,31(8):1893-1903
The precise polarization and orientation of developing neurons is essential for the correct wiring of the brain. In pyramidal excitatory neurons, polarization begins with the sprouting of opposite neurites, which later define directed migration and axo-dendritic domains. We here show that endogenous N-cadherin concentrates at one pole of the newborn neuron, from where the first neurite subsequently emerges. Ectopic N-cadherin is sufficient to favour the place of appearance of the first neurite. The Golgi and centrosome move towards this newly formed morphological pole in a second step, which is regulated by PI3K and the actin/microtubule cytoskeleton. Moreover, loss of function experiments in vivo showed that developing neurons with a non-functional N-cadherin misorient their cell axis. These results show that polarization of N-cadherin in the immediate post-mitotic stage is an early and crucial mechanism in neuronal polarity. 相似文献
182.
Moira L. Steyn-Ross D. Alistair Steyn-Ross Jamie W. Sleigh 《Cognitive neurodynamics》2012,6(3):215-225
During slow-wave sleep, general anesthesia, and generalized seizures, there is an absence of consciousness. These states are
characterized by low-frequency large-amplitude traveling waves in scalp electroencephalogram. Therefore the oscillatory state
might be an indication of failure to form coherent neuronal assemblies necessary for consciousness. A generalized seizure
event is a pathological brain state that is the clearest manifestation of waves of synchronized neuronal activity. Since gap
junctions provide a direct electrical connection between adjoining neurons, thus enhancing synchronous behavior, reducing
gap-junction conductance should suppress seizures; however there is no clear experimental evidence for this. Here we report
theoretical predictions for a physiologically-based cortical model that describes the general anesthetic phase transition
from consciousness to coma, and includes both chemical synaptic and direct electrotonic synapses. The model dynamics exhibits
both Hopf (temporal) and Turing (spatial) instabilities; the Hopf instability corresponds to the slow (≲8 Hz) oscillatory
states similar to those seen in slow-wave sleep, general anesthesia, and seizures. We argue that a delicately balanced interplay
between Hopf and Turing modes provides a canonical mechanism for the default non-cognitive rest state of the brain. We show
that the Turing mode, set by gap-junction diffusion, is generally protective against entering oscillatory modes; and that
weakening the Turing mode by reducing gap conduction can release an uncontrolled Hopf oscillation and hence an increased propensity
for seizure and simultaneously an increased sensitivity to GABAergic anesthesia. 相似文献
183.
Mi YJ Hou B Liao QM Ma Y Luo Q Dai YK Ju G Jin WL 《Cell death and differentiation》2012,19(7):1175-1186
Nogo-A is originally identified as an inhibitor of axon regeneration from the CNS myelin. Nogo-A is mainly expressed by oligodendrocytes, and also by some neuronal subpopulations, particularly in the developing nervous system. Although extensive studies have uncovered regulatory roles of Nogo-A in neurite outgrowth inhibition, precursor migration, neuronal homeostasis, plasticity and neurodegeneration, its cell-autonomous functions in neurons are largely uncharacterized. Here, we show that HIV-1 trans-activating-mediated amino-Nogo-A protein transduction into cultured primary cortical neurons achieves an almost complete neuroprotection against oxidative stress induced by exogenous hydrogen peroxide (H(2)O(2)). Endogenously expressed neuronal Nogo-A is significantly downregulated upon H(2)O(2) treatment. Furthermore, knockdown of Nogo-A results in more susceptibility to acute oxidative insults and markedly increases neuronal death. Interacting with peroxiredoxin 2 (Prdx2), amino-Nogo-A reduces reactive oxygen species (ROS) generation and extracellular signal-regulated kinase phosphorylation to exert neuroprotective effects. Structure-function mapping experiments reveal that, out of NiG-Δ20, a novel region comprising residues 290-562 of amino-Nogo-A is indispensable for preventing oxidative neuronal death. Moreover, mutagenesis analysis confirms that cysteine residues 424, 464 and 559 are involved in the inhibition of ROS generation and neuroprotective role of amino-Nogo-A. Our data suggest that neuronal Nogo-A might play a cell-autonomous role in improving neuronal survival against oxidative insult through interacting with Prdx2 and scavenging of ROS. 相似文献
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187.
This study isolated nine strains of aerobic phenol-degrading granules. These isolates (I1–I9) were characterized using 16S
rRNA gene sequencing, with γ-Proteobacteria as the dominant strains in the aerobic granules. While most strains demonstrated either high phenol-degrading capabilities
or auto-aggregation capabilities, three isolates, I2, I6, and I8 showed both features. These findings contradict the previous
view that auto-aggregation and phenol degradation are mutually exclusive in aerobic granules. Strains I2 and I8 independently
formed single-culture aerobic granules except for I3. Anti-microbial activity test results indicated that strains I2 and I8
inhibited growth of strain I3. However, co-culturing I3 with I2 or I8 helped to form granules. 相似文献
188.
189.
Eun-Seong Seo Camilla Christiansen Maher Abou Hachem Morten M. Nielsen Kenji Fukuda Sophie Bozonnet Andreas Blennow Nushin Aghajari Richard Haser Birte Svensson 《Biologia》2008,63(6):967-979
α-Glucans in general, including starch, glycogen and their derived oligosaccharides are processed by a host of more or less closely related enzymes that represent wide diversity in structure, mechanism, specificity and biological role. Sophisticated three-dimensional structures continue to emerge hand-in-hand with the gaining of novel insight in modes of action. We are witnessing the “test of time” blending with remaining questions and new relationships for these enzymes. Information from both within and outside of ALAMY_3 Symposium will provide examples on what the family contains and outline some future directions. In 2007 a quantum leap crowned the structural biology by the glucansucrase crystal structure. This initiates the disclosure of the mystery on the organisation of the multidomain structure and the “robotics mechanism” of this group of enzymes. The central issue on architecture and domain interplay in multidomain enzymes is also relevant in connection with the recent focus on carbohydrate-binding domains as well as on surface binding sites and their long underrated potential. Other questions include, how different or similar are glycoside hydrolase families 13 and 31 and is the lid finally lifted off the disguise of the starch lyase, also belonging to family 31? Is family 57 holding back secret specificities? Will the different families be sporting new “eccentric” functions, are there new families out there, and why are crystal structures of “simple” enzymes still missing? Indeed new understanding and discovery of biological roles continuously emphasize value of the collections of enzyme models, sequences, and evolutionary trees which will also be enabling advancement in design for useful and novel applications. 相似文献
190.
Similar to the situation in mammalian cells and yeast, messenger ribonucleo protein (mRNP) homeostasis in plant cells depends on rapid transitions between three functional states, i.e. translated mRNPs in polysomes, stored mRNPs and mRNPs under degradation. Studies in mammalian cells showed that whenever the dynamic exchange of the components between these states is disrupted, stalled mRNPs accumulate in cytoplasmic aggregates, such as stress granules (SGs) or processing bodies (PBs). We identified PBs and SGs in plant cells by detection of DCP1, DCP2 and XRN4, as marker proteins for the 5'-->3' mRNA degradation pathway, and eIF4E, as well as the RNA binding proteins RBP47 and UBP1, as marker proteins for stored mRNPs in SGs. Cycloheximide-inhibited translation, stress treatments and mutants defective in mRNP homeostasis were used to study the dynamic transitions of mRNPs between SGs and PBs. SGs and PBs can be clearly discriminated from the previously described heat stress granules (HSGs), which evidently do not contain mRNPs. Thus, the role of HSGs as putative mRNP storage sites must be revised. 相似文献