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151.
Structure and Function of the Hair Cell Ribbon Synapse 总被引:6,自引:0,他引:6
Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally
precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli
with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly
relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cell afferent
synapse — the electron-dense synaptic ribbon or synaptic body — has been recognized for decades, dissection of the synapse’s
molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms
underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear
and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding
the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years. 相似文献
152.
Feedback from community interactions involving mutualisms are a rarely explored mechanism for generating complex population
dynamics. We examined the effects of two linked mutualisms on the population dynamics of a beetle that exhibits outbreak dynamics.
One mutualism involves an obligate association between the bark beetle, Dendroctonus frontalis and two mycangial fungi. The second mutualism involves Tarsonemus mites that are phoretic on D. frontalis (“commensal”), and a blue-staining fungus, Ophiostoma minus. The presence of O. minus reduces beetle larval survival (“antagonistic”) by outcompeting beetle-mutualistic fungi within trees yet supports mite populations
by acting as a nutritional mutualist. These linked interactions potentially create an interaction system with the form of
an endogenous negative feedback loop. We address four hypotheses: (1) Direct negative feedback: Beetles directly increase
the abundance of O. minus, which reduces per capita reproduction of beetles. (2) Indirect negative feedback: Beetles indirectly increase mite abundance,
which increases O. minus, which decreases beetle reproduction. (3) The effect of O. minus on beetles depends on mites, but mite abundance is independent of beetle abundance. (4) The effect of O. minus on beetles is independent of beetle and mite abundance. High Tarsonemus and O. minus abundances were strongly correlated with the decline and eventual local extinction of beetle populations. Manipulation experiments
revealed strong negative effects of O. minus on beetles, but falsified the hypothesis that horizontal transmission of O. minus generates negative feedback. Surveys of beetle populations revealed that reproductive rates of Tarsonemus, O. minus, and beetles covaried in a manner consistent with strong indirect interactions between organisms. Co-occurrence of mutualisms
embedded within a community may have stabilizing effects if both mutualisms limit each other. However, delays and/or non-linearities
in the interaction systems may result in large population fluctuations.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
153.
Eisner G Moser M Schäfer U Beck K Müller M 《The Journal of biological chemistry》2006,281(11):7172-7179
Different from cytoplasmic membrane proteins, presecretory proteins of bacteria usually do not require the signal recognition particle for targeting to the Sec translocon. Nevertheless signal sequences of presecretory proteins have been found in close proximity to signal recognition particle immediately after they have emerged from the ribosome. We show here that at the ribosome, the molecular environment of a signal sequence depends on the nature of downstream sequence elements that can cause an alternate recruitment of signal recognition particle and the ribosome-associated chaperone Trigger factor to a growing nascent chain. While signal recognition particle and Trigger factor might remain bound to the same ribosome, both ligands are clearly able to displace each other from a nascent chain. The data also imply that a signal sequence owes its molecular environment to the fact that it remains closely apposed to the ribosomal exit site during growth of a nascent secretory protein. 相似文献
154.
Typically, c hemes are bound to the protein through two thioether bonds to cysteines and two axial ligands to the heme iron. In high-potential class I c-type cytochromes, these axial ligands are commonly His-Met. A change in this methionine axial ligand is often correlated with a dramatic drop in the heme redox potential and loss of function. Here we describe a bacterial cytochrome c with an unusual tolerance to the alternations in the heme ligation pattern. Substitution of the heme ligating methionine (M185) in cytochrome c1 of the Rhodobacter sphaeroides cytochrome bc1 complex with Lys and Leu lowers the redox midpoint potential but not enough to prevent physiologically competent electron transfer in these fully functional variants. Only when Met-185 is replaced with His is the drop in the redox potential sufficiently large to cause cytochrome bc1 electron transfer chain failure. Functional mutants preserve the structural integrity of the heme crevice: only the nonfunctional His variant allows carbon monoxide to bind to reduced heme, indicating a significant opening of the heme environment. This range of cytochrome c1 ligand mutants exposes both the relative resilience to sixth axial ligand change and the ultimate thermodynamic limits of operation of the cofactor chains in cytochrome bc1. 相似文献
155.
Path integration and the neural basis of the 'cognitive map' 总被引:1,自引:0,他引:1
McNaughton BL Battaglia FP Jensen O Moser EI Moser MB 《Nature reviews. Neuroscience》2006,7(8):663-678
The hippocampal formation can encode relative spatial location, without reference to external cues, by the integration of linear and angular self-motion (path integration). Theoretical studies, in conjunction with recent empirical discoveries, suggest that the medial entorhinal cortex (MEC) might perform some of the essential underlying computations by means of a unique, periodic synaptic matrix that could be self-organized in early development through a simple, symmetry-breaking operation. The scale at which space is represented increases systematically along the dorsoventral axis in both the hippocampus and the MEC, apparently because of systematic variation in the gain of a movement-speed signal. Convergence of spatially periodic input at multiple scales, from so-called grid cells in the entorhinal cortex, might result in non-periodic spatial firing patterns (place fields) in the hippocampus. 相似文献
156.
P450 BM3: the very model of a modern flavocytochrome 总被引:4,自引:0,他引:4
Munro AW Leys DG McLean KJ Marshall KR Ost TW Daff S Miles CS Chapman SK Lysek DA Moser CC Page CC Dutton PL 《Trends in biochemical sciences》2002,27(5):250-257
Flavocytochrome P450 BM3 is a bacterial P450 system in which a fatty acid hydroxylase P450 is fused to a mammalian-like diflavin NADPH-P450 reductase in a single polypeptide. The enzyme is soluble (unlike mammalian P450 redox systems) and its fusion arrangement affords it the highest catalytic activity of any P450 mono-oxygenase. This article discusses the fundamental properties of P450 BM3 and how progress with this model P450 has affected our comprehension of P450 systems in general. 相似文献
157.
8-Aryl xanthines potent inhibitors of phosphodiesterase 5 总被引:1,自引:0,他引:1
Arnold R Beer D Bhalay G Baettig U Collingwood SP Craig S Devereux N Dunstan A Glen A Gomez S Haberthuer S Howe T Jelfs S Moser H Naef R Nicklin P Sandham D Stringer R Turner K Watson S Zurini M 《Bioorganic & medicinal chemistry letters》2002,12(18):2587-2590
In clinical studies, several inhibitors of phosphodiesterase 5 (PDE5) have demonstrated utility in the treatment of erectile dysfunction. We describe herein a series of 8-aryl xanthine derivatives which function as potent PDE5 inhibitors with, in many cases, high levels of selectivity versus other PDE isoforms. 相似文献
158.
Williams GD Andrews KS Katz SL Moser ML Tolimieri N Farrer DA Levin PS 《Journal of fish biology》2012,80(5):1380-1400
The detailed movements of 32 acoustically tagged broadnose sevengill shark Notorynchus cepedianus were documented in and around north-east Pacific Ocean estuarine embayments from 2005 to 2007. Arrangements of passive acoustic receivers allowed analysis of movement at several spatial scales, with sex and size examined as possible factors influencing the pattern and timing of these movements. Notorynchus cepedianus exhibited a distinctly seasonal pattern of estuary use over three consecutive years, entering Willapa Bay in the spring, residing therein for extended periods of time during the summer and dispersing into nearshore coastal habitats and over the continental shelf during the autumn. Notorynchus cepedianus within Willapa Bay showed spatio-temporal patterns of segregation by size and sex, with males and small females using peripheral southern estuary channels early in the season before joining large females, who remained concentrated in central estuary channels for the entire season. Individuals displayed a high degree of fidelity not only to Willapa Bay (63% were documented returning over three consecutive seasons), but also to specific areas within the estuary, showing consistent patterns of site use from year to year. Cross-estuary movement was common during the summer, with most fish also moving into an adjacent estuarine embayment for some extent of time. Most winter and autumn coastal detections of N. cepedianus were made over the continental shelf near Oregon and Washington, U.S.A., but there were also examples of individuals moving into nearshore coastal habitats further south into California, suggesting the feasibility of broad-scale coastal movements to known birthing and nursery grounds for the species. These findings contribute to a better understanding of N. cepedianus movement ecology, which can be used to improve the holistic management of this highly mobile apex predator in regional ecosystems. 相似文献
159.
Moser B Bekos C Zimprich F Nickl S Klepetko W Ankersmit J 《Biochemical and biophysical research communications》2012,420(1):96-101
ObjectiveMyasthenia gravis (MG) is a T- and B-cell mediated autoimmune disorder affecting the neuromuscular junction. The receptor for advanced glycation endproducts (RAGE) plays a role in the amplification of chronic inflammatory disorders and autoimmune diseases. We sought to investigate the role of RAGE and its ligands in the pathophysiology of MG.MethodsIn this cross-sectional study we enrolled 42 patients with MG and 36 volunteers. We employed enzyme-linked immunosorbent assays to determine the concentration of soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1) in serum of patients and volunteers. In a subpopulation of patients we measured the serum levels of endogenous secretory (es) RAGE and various RAGE ligands, such as S100B, S100A8 and advanced glycation endproducts (AGE-CML). Reported are means and standard error mean.ResultsWe found significantly reduced levels of the soluble receptors sRAGE and esRAGE in patients with MG compared to volunteers without MG (sRAGE [pg/ml] 927.2 ± 80.8 vs. 1400.1 ± 92.4; p < 0.001; esRAGE [pg/ml] 273.5 ± 24.6 vs. 449.0 ± 22.4; p < 0.001). Further categorization of patients with MG according to the distribution of muscle involvement revealed the following sRAGE concentrations: generalized MG 999.4 ± 90.8 and ocular MG 696.1 ± 161.8 (vs. control; One-way ANOVA: p < 0.001; Post hoc analysis: generalized vs. ocular MG: p = 0.264, generalized MG vs. control: p = 0.008, ocular MG vs. control: p = 0.001). In patients with detectable antibodies specific for acetylcholine receptors (Anti-AChR positive) the sRAGE concentration was 970.0 ± 90.2 compared to those without (seronegative) 670.6 ± 133.1 (vs. control; One-way ANOVA: p < 0.001; Post hoc analysis: Pos vs. Neg.: p = 0.418, Pos vs. control: p = 0.003, Neg. vs. control: p = 0.008). We next investigated the role of RAGE ligands in MG. The concentrations of RAGE ligands in patients with MG and controls were as follows: (HMGB1 [ng/ml] 1.7 ± 0.1 vs. 2.1 ± 0.2; p = 0.058; S100B [pg/ml] 22.5 ± 22.5 vs. 14.4 ± 9.2; p = 0.698; S100A8 [pg/ml] 107.0 ± 59.3 vs. 242.5 ± 103.6; p = 0.347; and AGE-CML [ng/ml] 1100.8 ± 175.1 vs. 1399.8 ± 132.8; p = 0.179).ConclusionsOur data suggest a role for the RAGE pathway in the pathophysiology of MG. Further studies are warranted to elucidate more about this immunological axis in patients with MG. 相似文献