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1.
The responses to visual stimuli of simple cortical cells show linear spatial summation within and between their receptive field subunits. Complex cortical cells do not show this linearity. We analyzed the simulated responses to drifting sinusoidal grating stimuli of simple and of several types of complex cells. The complex cells, whose responses are seen to be half-wave rectified before pooling, have receptive fields consisting of two or more DOG (difference-of-Gaussians) shaped subunits. In both cases of stimulation by contrast-reversal gratings or drifting gratings, the cells' response as a function of spatial frequency is affected by the subunit distances 2 and the stimulation frequency . Furthermore, an increased number of subunits (a larger receptive field) yields a narrower peak tuning curve with decreased modulation depth for many of the spatial frequencies. The average and the peak response tuning curves are compared for the different receptive field types. 相似文献
2.
Paolo Gaudiano Andrzej W. Przybyszewski Richard J. A. van Wezel Wim A. van de Grind 《Biological cybernetics》1998,79(2):151-159
. Enroth-Cugell and Robson (1966) first proposed a classification of retinal ganglion cells into X cells, which exhibit approximate
linear spatial summation and largely sustained responses, and Y cells, which exhibit nonlinearities and transient responses.
Gaudiano (1992a, 1992b, 1994) has suggested that the dominant characteristics of both X and Y cells can be simulated with
a single model simply by changing receptive field profiles to match those of the anatomical counterparts of X and Y cells.
He also proposed that a significant component of the spatial nonlinearities observed in Y (and sometimes X) cells can result
from photoreceptor nonlinearities coupled with push-pull bipolar connections. Specifically, an asymmetry was predicted in
the ganglion cell response to rectangular gratings presented at different locations in the receptive field under two conditions:
introduction/withdrawal (on-off) or contrast reversal. When measuring the response to these patterns as a function of spatial
phase, the standard difference-of-Gaussians model predicts symmetrical responses about the receptive field center, while the
push-pull model predicts slight but significant asymmetry in the on-off case only. To test this hypothesis, we have recorded
ganglion cell responses from the optic tract fibers of anesthetized cat. The mean and standard deviations of responses to
on-off and contrast-reversed patterns were compared. We found that all but one of the cells that yielded statistically significant
data confirmed the hypothesis. These results largely support the theoretical prediction.
Received: 21 March 1997 / Accepted in revised form: 6 May 1998 相似文献
3.
Oranit Dror Dina Schneidman-Duhovny Alexandra Shulman-Peleg Ruth Nussinov Haim J Wolfson Roded Sharan 《BMC systems biology》2008,2(1):1-7
Background
The functions of a eukaryotic cell are largely performed by multi-subunit protein complexes that act as molecular machines or information processing modules in cellular networks. An important problem in systems biology is to understand how, in general, these molecular machines respond to perturbations.Results
In yeast, genes that inhibit growth when their expression is reduced are strongly enriched amongst the subunits of multi-subunit protein complexes. This applies to both the core and peripheral subunits of protein complexes, and the subunits of each complex normally have the same loss-of-function phenotypes. In contrast, genes that inhibit growth when their expression is increased are not enriched amongst the core or peripheral subunits of protein complexes, and the behaviour of one subunit of a complex is not predictive for the other subunits with respect to over-expression phenotypes.Conclusion
We propose the principle that the overall activity of a protein complex is in general robust to an increase, but not to a decrease in the expression of its subunits. This means that whereas phenotypes resulting from a decrease in gene expression can be predicted because they cluster on networks of protein complexes, over-expression phenotypes cannot be predicted in this way. We discuss the implications of these findings for understanding how cells are regulated, how they evolve, and how genetic perturbations connect to disease in humans. 相似文献4.
We systematically classified goldfish ganglion cells according to their spatial summation properties using the same techniques and criteria used in cat and monkey research. Results show that goldfish ganglion cells can be classified as X-, Y-, or W-like based on their responses to contrast-reversal gratings. Like cat X cells, goldfish X-like cells display linear spatial summation. Goldfish Y-like cells, like cat Y cells, respond with frequency doubling at all spatial positions when the contrast-reversal grating consists of high spatial frequencies. There is also a third class of neurons, which is neither X- nor Y-like; many of these cells' properties are similar to those of the "not-X" cells found in the eel retina. Spatial filtering characteristics were obtained for each cell by drifting sinusoidal gratings of various spatial frequencies and contrasts across the receptive field of the cell at a constant temporal rate. The spatial tuning curves of the cell depend on the temporal parameters of the stimulus; at high drift rates, the tuning curves lose their low spatial frequency attenuation. To explore this phenomenon, temporal contrast response functions were derived from the cells' responses to a spatially uniform field whose luminance varied sinusoidally in time. These functions were obtained for the center, the surround, and the entire receptive field. The results suggest that differences in the cells' spatial filtering across stimulus drift rate are due to changes in the interaction of the center and surround mechanisms; at low temporal frequencies, the center and surround responses are out-of-phase and mutually antagonistic, but at higher temporal rates their responses are in-phase and their interaction actually enhances the cell's responsiveness. 相似文献
5.
Miyyada Boumechache Marianela Masin J. Michael Edwardson Dariusz C. G��recki Ruth Murrell-Lagnado 《The Journal of biological chemistry》2009,284(20):13446-13454
P2X4 and P2X7 are the predominant P2X receptor subtypes expressed in immune
cells. Having previously shown a structural and functional interaction between
the two recombinant receptors, our aims here were to identify the preferred
assembly pathway of the endogenous receptors in macrophage-like cells and to
investigate the trafficking of these receptors between the plasma membrane and
intracellular sites. We exploited the difference in size between the two
subunits, and we used a combination of cross-linkers and blue native-PAGE
analysis to investigate the subunit composition of complexes present in
primary cultures of rat microglia and macrophages from wild type and
P2X7–/– mice. Our results indicate that the preferred
assembly pathway for both receptors is the formation of homotrimers.
Homotrimers of P2X7 were able to co-immunoprecipitate with P2X4, suggesting
that an interaction occurs between rather than within receptor complexes. In
both macrophages and microglia, P2X7 receptors were predominantly at the cell
surface, whereas P2X4 receptors were predominantly intracellular. There were
clear cell type-dependent differences in the extent to which P2X4 receptors
trafficked to and from the surface; trafficking was much more dynamic in
microglia than in the macrophages, and further activation of cultured
microglia with relatively short (3-h) incubations with lipopolysaccharide
caused an ∼4-fold increase in the fraction of receptors at the surface
with only a 1.2-fold increase in total expression. The redistribution of
intracellular receptors is thus an efficient means of enhancing the functional
expression of P2X4 at the plasma membrane of microglia.Acting via P2X receptors, ATP has several effects on immune cells,
including triggering the release of pro-inflammatory cytokines, programmed
cell death, and mycobacterial killing
(1,
2). Until recently, attention
has focused on the P2X7 receptor as the relevant sensor at the cell surface,
and there is evidence for its involvement in neuropathic and inflammatory pain
(3), arthritis
(4), and the control of
mycobacterial infection (5).
P2X7 has a low affinity for ATP compared with the other predominant subtype
expressed by immune cells, P2X4. The role of P2X4 receptors is less well
understood, although in microglia they were shown to be up-regulated following
peripheral nerve injury and to play an important role in the development of
neuropathic pain (6).
Regulation of the plasma membrane expression of these two receptors is not
understood. Also, despite the considerable interest in both these receptor
subtypes as potential targets in development of novel pain therapies, the
subunit composition of the native receptors has not been determined.P2X receptor subunits associate to form trimeric complexes around a central
conduction pore (7,
8). With the exception of P2X6,
they form functional homomeric receptors, and several subtypes also form
functional heterotrimers (9).
There is also evidence that P2X receptors form larger signaling complexes,
interacting with other neighboring P2X receptors and also with ion channels
that belong to different structural classes, including members of the Cys loop
receptor family (10) and the
gap junction family (11).
Higher order structures, with molecular mass corresponding to hexamers and
nonamers, have been identified for heterologously expressed P2X2 and P2X4
receptors, suggesting that two or three receptors can form a stable
association (12). Consistent
with this idea, P2X receptor channels within a patch of membrane have been
shown to open in a non-independent manner and to display positive
cooperativity (13,
14).P2X4 and P2X7 are frequently co-expressed, not only in immune cells but
also in epithelia and endothelia
(15). The P2X7 subtype differs
from other members of the family in that it has a very long cytoplasmic
C-terminal tail, a low affinity toward ATP, is preferentially activated by
BzATP, and couples to the opening of a pore permeable to large molecules up to
900 Da (2). P2X4 receptors have
considerably higher affinity for ATP; they are up-regulated by the allosteric
modulator ivermectin and are sensitive to the antagonist
TNP-ATP3 at micromolar
concentrations. It has been widely assumed that P2X7 does not form heteromeric
assemblies with other members of the P2X family; however, recent evidence has
indicated a structural and functional interaction between P2X4 and P2X7
receptors. First, P2X receptor currents recorded from airway-ciliated cells
were reported to show a combination of P2X4-like and P2X7-like properties
(16). Second, we showed that
P2X4 and P2X7 could be co-immunoprecipitated both from mouse bone
marrow-derived macrophages (BMDMs) and also when heterologously co-expressed
(17). In addition, we used two
nonfunctional point mutants of P2X4 to demonstrate a functional interaction
between the two receptors; one mutant exerted a dominant negative effect on
P2X7 receptor currents, whereas another conferred P2X4-like properties on the
whole cell currents, namely sensitivity to ivermectin and TNP-ATP. Our
conclusion was that P2X4 and P2X7 form a heteromeric association but that it
remained to be established whether or not they assemble as heterotrimers
around the same conduction pore.In this study, we set out first to address the question of the preferred
assembly pathway of native P2X4 and P2X7 receptors in immune cells, and second
to compare how these receptors traffic within immune cells. We took advantage
of the size difference between P2X4 and P2X7 subunits to analyze the
composition of the predominant dimeric and trimeric forms. We found that in
rodent macrophages and microglia, P2X4 and P2X7 receptors preferentially
assemble as homotrimers. Comparison of the trafficking of these receptors
indicated cell type-dependent differences in the extent to which the
predominantly intracellular P2X4 receptor traffics to and from the
surface. 相似文献
6.
De M Jayarapu K Elenich L Monaco JJ Colbert RA Griffin TA 《The Journal of biological chemistry》2003,278(8):6153-6159
Vertebrate proteasomes are structurally heterogeneous, consisting of both "constitutive" (or "standard") proteasomes and "immunoproteasomes." Constitutive proteasomes contain three ubiquitously expressed catalytic subunits, Delta (beta 1), Z (beta 2), and X (beta 5), whereas immunoproteasomes contain three interferon-gamma-inducible catalytic subunits, LMP2 (beta 1i), MECL (beta 2i), and LMP7 (beta 5i). We recently have demonstrated that proteasome assembly is biased to promote immunoproteasome homogeneity when both types of catalytic subunits are expressed in the same cell. This cooperative assembly is due in part to differences between the LMP7 (beta 5i) and X (beta 5) propeptides. In the current study we demonstrate that differences between the MECL (beta 2i) and Z (beta2) propeptides also influence cooperative assembly. Specifically, replacing the MECL propeptide with that of Z enables MECL incorporation into otherwise constitutive (Delta(+)/X(+)) proteasomes and facilitates X incorporation into otherwise immunoproteasomes (MECL(+)/LMP2(+)). We also show, using MECL(-/-) mice, that LMP2 incorporation does not require MECL, in contrast with previous suggestions that their incorporation is mutually codependent. These results enable us to refine our model for cooperative proteasome assembly by determining which combinations of inducible and constitutive subunits are favored over others, and we propose a mechanism for how propeptides mediate cooperative assembly. 相似文献
7.
Gamma oscillations (30 to 80 Hz) have been hypothesized to play an important role in feature binding, based on the observation that continuous long bars induce stronger gamma in the visual cortex than bars with a small gap. Recently, many studies have shown that natural images, which have discontinuities in several low-level features, do not induce strong gamma oscillations, questioning their role in feature binding. However, the effect of different discontinuities on gamma has not been well studied. To address this, we recorded spikes and local field potential from 2 monkeys while they were shown gratings with discontinuities in 4 attributes: space, orientation, phase, or contrast. We found that while these discontinuities only had a modest effect on spiking activity, gamma power drastically reduced in all cases, suggesting that gamma could be a resonant phenomenon. An excitatory–inhibitory population model with stimulus-tuned recurrent inputs showed such resonant properties. Therefore, gamma could be a signature of excitation–inhibition balance, which gets disrupted due to discontinuities.Gamma oscillations (30-80 Hz) in visual cortex have been hypothesized to play an important role in feature binding, but this role has recently been questioned. This study shows that visual stimulus-induced gamma oscillations are highly attenuated with even small discontinuities in the stimulus. This "resonant" behaviour can be explained by a simple excitatory-inhibitory model in which discontinuities lead to a small reduction in lateral inputs. 相似文献
8.
Wang B Norbury CC Greenwood R Bennink JR Yewdell JW Frelinger JA 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(3):1283-1289
CD8(+) CTLs play a pivotal role in immune responses against many viruses and tumors. Two models have been proposed. The "three-cell" model focuses on the role of CD4(+) T cells, proposing that help is only provided to CTLs by CD4(+) T cells that recognize Ag on the same APC. The sequential "two-cell" model proposes that CD4(+) T cells can first interact with APCs, which in turn activate naive CTLs. Although these models provide a general framework for the role of CD4(+) T cells in mediating help for CTLs, a number of issues are unresolved. We have investigated the induction of CTL responses using dendritic cells (DCs) to immunize mice against defined peptide Ags. We find that help is required for activation of naive CTLs when DCs are used as APCs, regardless of the origin or MHC class I restriction of the peptides we studied in this system. However, CD8(+) T cells can provide self-help if they are present at a sufficiently high precursor frequency. The important variable is the total number of T cells responding, because class II-knockout DCs pulsed with two noncompeting peptides are effective in priming. 相似文献
9.
We outline a scheme for the way in which early vision may handle information about shading (luminance modulation, LM) and texture (contrast modulation, CM). Previous work on the detection of gratings has found no sub-threshold summation, and no cross-adaptation, between LM and CM patterns. This strongly implied separate channels for the detection of LM and CM structure. However, we now report experiments in which adapting to LM (or CM) gratings creates tilt aftereffects of similar magnitude on both LM and CM test gratings, and reduces the perceived strength (modulation depth) of LM and CM gratings to a similar extent. This transfer of aftereffects between LM and CM might suggest a second stage of processing at which LM and CM information is integrated. The nature of this integration, however, is unclear and several simple predictions are not fulfilled. Firstly, one might expect the integration stage to lose identity information about whether the pattern was LM or CM. We show instead that the identity of barely detectable LM and CM patterns is not lost. Secondly, when LM and CM gratings are combined in-phase or out-of-phase we find no evidence for cancellation, nor for 'phase-blindness'. These results suggest that information about LM and CM is not pooled or merged--shading is not confused with texture variation. We suggest that LM and CM signals are carried by separate channels, but they share a common adaptation mechanism that accounts for the almost complete transfer of perceptual aftereffects. 相似文献
10.
Michael W. Metzger Sandra M. Walser Fernando Aprile-Garcia Nina Dedic Alon Chen Florian Holsboer Eduardo Arzt Wolfgang Wurst 《Purinergic signalling》2017,13(2):153-170
The purinergic P2X7 receptor (P2X7R) has attracted considerable interest as a potential target for various central nervous system (CNS) pathologies including affective and neurodegenerative disorders. To date, the distribution and cellular localization of the P2X7R in the brain are not fully resolved and a matter of debate mainly due to the limitations of existing tools. However, this knowledge should be a prerequisite for understanding the contribution of the P2X7R to brain disease. Here, we generated a genetic mouse model by humanizing the P2X7R in the mouse as mammalian model organism. We demonstrated its functionality and revealed species-specific characteristics of the humanized receptor, compared to the murine ortholog, regarding its receptivity to activation and modulation by 2′,3′-O-(benzoyl-4-benzoyl)-adenosine 5′-triphosphate (BzATP) and trifluoperazine (TFP). This humanized P2rx7 allele is accessible to spatially and temporally controlled Cre recombinase-mediated inactivation. In contrast to previously generated knockout (KO) mice, none of the described P2rx7 splice variants evade this null allele. By selective disruption and assessment of human P2RX7 expression in different brain regions and cell types, we were able to demonstrate that the P2X7R is specifically expressed in glutamatergic pyramidal neurons of the hippocampus. Also, P2X7R is expressed in major non-neuronal lineages throughout the brain, i.e., astrocytes, oligodendrocytes, and microglia. In conclusion, this humanized mouse model provides the means for detailed assessment of human P2X7R function in vivo including evaluation of agonists or antagonists. In addition, this conditional allele will enable future loss-of-function studies in conjunction with mouse models for CNS disorders. 相似文献
11.
A. Concas R. Imperatore F. Santoru A. Locci P. Porcu L. Cristino P. Pierobon 《Neurochemical research》2016,41(11):2914-2922
γ-aminobutyric acid (GABA) receptors, responding to GABA positive allosteric modulators, are present in the freshwater polyp Hydra vulgaris (Cnidaria, Hydrozoa), one of the most primitive metazoans to develop a nervous system. We examined the occurrence and distribution of GABAA receptor subunits in Hydra tissues by western blot and immunohistochemistry. Antibodies against different GABAA receptor subunits were used in Hydra membrane preparations. Unique protein bands, inhibited by the specific peptide, appeared at 35, 60, ~50 and ~52 kDa in membranes incubated with α3, β1, γ3 or δ antibodies, respectively. Immunohistochemical screening of whole mount Hydra preparations revealed diffuse immunoreactivity to α3, β1 or γ3 antibodies in tentacles, hypostome, and upper part of the gastric region; immunoreactive fibers were also present in the lower peduncle. By contrast, δ antibodies revealed a strong labeling in the lower gastric region and peduncle, as well as in tentacles. Double labeling showed colocalization of α3/β1, α3/γ3 and α3/δ immunoreactivity in granules or cells in tentacles and gastric region. In the peduncle, colocalization of both α3/β1 and α3/γ3 immunoreactivity was found in fibers running horizontally above the foot. These data indicate that specific GABAA receptor subunits are present and differentially distributed in Hydra body regions. Subunit colocalization suggests that Hydra GABA receptors are heterologous multimers, possibly sub-serving different physiological activities. 相似文献
12.
Patricia Gibert Matthew Hill Marta Pascual Christophe Plantamp John S. Terblanche Amir Yassin Carla M. Sgrò 《Biological invasions》2016,18(4):1089-1103
The last few decades have seen a growing number of species invasions globally, including many insect species. In drosophilids, there are several examples of successful invasions, i.e. Zaprionus indianus and Drosophila subobscura some decades ago, but the most recent and prominent example is the invasion of Europe and North America by the pest species, Drosophila suzukii. During the invasive process, species often encounter diverse environmental conditions that they must respond to, either through rapid genetic adaptive shifts or phenotypic plasticity, or by some combination of both. Consequently, invasive species constitute powerful models for investigating various questions related to the adaptive processes that underpin successful invasions. In this paper, we highlight how Drosophila have been and remain a valuable model group for understanding these underlying adaptive processes, and how they enable insight into key questions in invasion biology, including how quickly adaptive responses can occur when species are faced with new environmental conditions. 相似文献
13.
H. Marko 《Biological cybernetics》1981,39(2):111-123
By considering only the modulation transfer functions of stationary, uniformly moved, and time modulated sinusoidal gratings it is possible to derive a simple model, the z-model, for the spatio-temporal frequency behaviour of one-dimensional patterns. The transmission function of this model is a band pass function of a single coordinate z, which is a quadratic form of the spatial and temporal frequencies (rotational symmetry with respect to space and time). The model is determined by only three constants. Optionally a time phase which accounts for delay and phase distortion can be added. This model can also be derived from reaction time measurements for switched on sinusoidal gratings. With this model the response of a wide variety of spatio-temporal patterns have been calculated and compared with measured threshold data. For two-dimensional patterns orientational filtering has to be added to the model leading to a further parameter. This model predicts satisfactorily the threshold modulation for a great variety of arbitrary spatio-temporal patterns. However the absolute threshold value for aperiodic transient patterns differs slightly in direction of smaller sensitivity as compared with periodic stationary patterns. This suggests that the peak detection scheme usually used in threshold detection modeling should be replaced by an integrative mechanism. 相似文献
14.
Hans-Arne Hansson 《Cell and tissue research》1970,107(2):199-209
Summary The three-dimensional arrangement of the zonular fibers of Zinn and their ultrastructure was studied with the aid of scanning and transmission electron microscopy.Most of the thicker zonular fibers are arranged in straight bundles between the ciliary body and the lens, while the thinner fibers form a complex three-dimensional network interconnecting all the zonular fibers. These do originate from the limiting membrane covering the ciliary body. The zonular fibers are subdivided close to lens and form a complicated network on the surface of the lens capsule, i. e. the zonular lamella. The latter consists of a dense network of fibers and is from a structural point of view closely related to the zonular fibers and not to the lens capsule.The zonular fibers are continuous with those in the vitreous body close to the ciliary body but never in the lenticular two thirds of the zonular fibers or in the retrolental area.The ground substance is possible to demonstrate in freeze-dried specimens by scanning electron microscopy. It appeared granular or amorphous and coated the zonular fibers. It does not form membranes or fill all available space in contrast to its properties in the vitreous body. The many structural similarities between the zonular fibers and the vitreous body indicate perhaps a common origin.Supported by grants from Magnus Bergwalls Stiftelse and the Swedish Medical Research Council (B70-12 X -2543-02, B71-12 X -2543-03). 相似文献
15.
Background
How the visual system combines information from the two eyes to form a unitary binocular representation of the external world is a fundamental question in vision science that has been the focus of many psychophysical and physiological investigations. Ding & Sperling (2006) measured perceived phase of the cyclopean image, and developed a binocular combination model in which each eye exerts gain control on the other eye''s signal and over the other eye''s gain control. Critically, the relative phase of the monocular sine-waves plays a central role.Methodology/Principal Findings
We used the Ding-Sperling paradigm but measured both the perceived contrast and phase of cyclopean images in three hundred and eighty combinations of base contrast, interocular contrast ratio, eye origin of the probe, and interocular phase difference. We found that the perceived contrast of the cyclopean image was independent of the relative phase of the two monocular gratings, although the perceived phase depended on the relative phase and contrast ratio of the monocular images. We developed a new multi-pathway contrast-gain control model (MCM) that elaborates the Ding-Sperling binocular combination model in two ways: (1) phase and contrast of the cyclopean images are computed in separate pathways, although with shared cross-eye contrast-gain control; and (2) phase-independent local energy from the two monocular images are used in binocular contrast combination. With three free parameters, the model yielded an excellent account of data from all the experimental conditions.Conclusions/Significance
Binocular phase combination depends on the relative phase and contrast ratio of the monocular images but binocular contrast combination is phase-invariant. Our findings suggest the involvement of at least two separate pathways in binocular combination. 相似文献16.
The membrane-bound complex of the prokaryotic histidine permease, a periplasmic protein-dependent ABC transporter, is composed of two hydrophobic subunits, HisQ and HisM, and two identical ATP-binding subunits, HisP, and is energized by ATP hydrolysis. The soluble periplasmic binding protein, HisJ, creates a signal that induces ATP hydrolysis by HisP. The crystal structure of HisP has been resolved and shown to have an "L" shape, with one of its arms (arm I) being involved in ATP binding and the other one (arm II) being proposed to interact with the hydrophobic subunits (Hung, L.-W., Wang, I. X., Nikaido, K., Liu, P.-Q., Ames, G. F.-L., and Kim, S.-H. (1998) Nature 396, 703-707). Here we study the basis for the defect of several HisP mutants that have an altered signaling pathway and hydrolyze ATP constitutively. We use biochemical approaches to show that they produce a loosely assembled membrane complex, in which the mutant HisP subunits are disengaged from HisQ and HisM, suggesting that the residues involved are important in the interaction between HisP and the hydrophobic subunits. In addition, the mutant HisPs are shown to have lower affinity for ADP and to display no cooperativity for ATP. All of the residues affected in these HisP mutants are located in arm II of the crystal structure of HisP, thus supporting the proposed function of arm II of HisP as interacting with HisQ and HisM. A revised model involving a cycle of disengagement and reengagement of HisP is proposed as a general mechanism of action for ABC transporters. 相似文献
17.
Ondej Podrazký Pavel Peterka Ivan Kaík Soa Vytyk
ov Jana Probotov Jan Mrzek Martin Kune Veronika Zvalov Vra Radochov Oleksiy Lyutakov Edoardo Ceci‐Ginistrelli Diego Pugliese Nadia G. Boetti Davide Janner Daniel Milanese 《Journal of biophotonics》2019,12(7)
Optical fibers have recently attracted a noticeable interest for biomedical applications because they provide a minimally invasive method for in vivo sensing, imaging techniques, deep‐tissue photodynamic therapy or optogenetics. The silica optical fibers are the most commonly used because they offer excellent optical properties, and they are readily available at a reasonable price. The fused silica is a biocompatible material, but it is not bioresorbable so it does not decompose in the body and the fibers must be ex‐planted after in vivo use and their fragments can present a considerable risk to the patient when the fiber breaks. In contrast, optical fibers made of phosphate glasses can bring many benefits because such glasses exhibit good transparency in ultraviolet‐visible and near‐infrared regions, and their solubility in water can be tailored by changing the chemical composition. The bioresorbability and toxicity of phosphate glass–based optical fibers were tested in vivo on male laboratory rats for the first time. The fiber was spliced together with a standard graded‐index multi‐mode fiber pigtail and an optical probe for in vitro pH measurement was prepared by the immobilization of a fluorescent dye on the fiber tip by a sol‐gel method to demonstrate applicability and compatibility of the fiber with common fiber optics. 相似文献
18.
Human P2X2 receptors (hP2X2) are strongly inhibited by zinc over the range of 2–100 μm, whereas rat P2X2 receptors (rP2X2) are strongly potentiated over the same range, and then inhibited by zinc over 100 μm. However, the biological role of zinc modulation is unknown in either species. To identify candidate regions controlling zinc inhibition in hP2X2 a homology model based on the crystal structure of zebrafish P2X4.1 was made. In this model, His-204 and His-209 of one subunit were near His-330 of the adjacent subunit. Cross-linking studies confirmed that these residues are within 8 Å of each other. Simultaneous mutation of these three histidines to alanines decreased the zinc potency of hP2X2 nearly 100-fold. In rP2X2, one of these histidines is replaced by a lysine, and in a background in which zinc potentiation was eliminated, mutation of Lys-197 to histidine converted rP2X2 from low potency to high potency inhibition. We explored whether the zinc-binding site lies within the vestibules running down the central axis of the receptor. Elimination of all negatively charged residues from the upper vestibule had no effect on zinc inhibition. In contrast, mutation of several residues in the hP2X2 middle vestibule resulted in dramatic changes in the potency of zinc inhibition. In particular, the zinc potency of P206C could be reversibly shifted from extremely high (∼10 nm) to very low (>100 μm) by binding and unbinding MTSET. These results suggest that the cluster of histidines at the subunit interface controls access of zinc to its binding site. 相似文献
19.
To what extent are sensory responses in the brain compatible with first-order principles? The efficient coding hypothesis projects that neurons use as few spikes as possible to faithfully represent natural stimuli. However, many sparsely firing neurons in higher brain areas seem to violate this hypothesis in that they respond more to familiar stimuli than to nonfamiliar stimuli. We reconcile this discrepancy by showing that efficient sensory responses give rise to stimulus selectivity that depends on the stimulus-independent firing threshold and the balance between excitatory and inhibitory inputs. We construct a cost function that enforces minimal firing rates in model neurons by linearly punishing suprathreshold synaptic currents. By contrast, subthreshold currents are punished quadratically, which allows us to optimally reconstruct sensory inputs from elicited responses. We train synaptic currents on many renditions of a particular bird''s own song (BOS) and few renditions of conspecific birds'' songs (CONs). During training, model neurons develop a response selectivity with complex dependence on the firing threshold. At low thresholds, they fire densely and prefer CON and the reverse BOS (REV) over BOS. However, at high thresholds or when hyperpolarized, they fire sparsely and prefer BOS over REV and over CON. Based on this selectivity reversal, our model suggests that preference for a highly familiar stimulus corresponds to a high-threshold or strong-inhibition regime of an efficient coding strategy. Our findings apply to songbird mirror neurons, and in general, they suggest that the brain may be endowed with simple mechanisms to rapidly change selectivity of neural responses to focus sensory processing on either familiar or nonfamiliar stimuli. In summary, we find support for the efficient coding hypothesis and provide new insights into the interplay between the sparsity and selectivity of neural responses. 相似文献
20.
Jensen LJ Skovgaard M Sicheritz-Pontén T Jørgensen MK Lundegaard C Pedersen CC Petersen N Ussery D 《BMC genomics》2003,4(1):12