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1.
The responses of Limulus optic nerve fibers to patterns of illumination on the receptor mosaic
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The inhibition that is exerted mutually among receptor units (ommatidia) of the compound eye of Limulus is less for units widely separated than for those close together. This diminution of inhibition with distance is the resultant of two factors: (1) the threshold of inhibitory action increases with increasing distance between the units involved; and (2) the coefficient of inhibitory action decreases with increasing distance. The discharge of nerve impulses from ommatidia at various distances from one another may be described quantitatively by a set of simultaneous linear equations which express the excitatory effects of the illumination on each ommatidium and the inhibitory interactions between each ommatidium and its neighbors. The values of the thresholds and coefficients of inhibitory action, which appear as parameters in these equations, must be determined empirically: their dependence on distance is somewhat irregular and cannot yet be expressed in an exact general law. Nevertheless the diminution of inhibitory influences with distance is sufficiently uniform that patterns of neural response generated by various patterns of illumination on the receptor mosaic can be predicted qualitatively. Such predictions have been verified experimentally for two simple patterns of illumination: an abrupt step in intensity, and a simple gradient between two levels of intensity (the so-called Mach pattern). In each case, transitions in the pattern of illumination are accentuated in the corresponding pattern of neural response. 相似文献
2.
Dezsö Von Vakjú 《Biological cybernetics》1962,1(5):200-208
Summary Two semi-linear models for lateral inhibition are discussed. The interaction between receptor units is assumed to be linear, as demonstrated by Hartline and Ratliff in the eye of the horseshoe crab Limulus polyphemus. Yet a model of such an inhibitory system must be nonlinear, since the output values correspond to nerve activities, which cannot be negativ. Models with forward inhibition were used often to describe contrast phenomena in the human nervous system. However, in order to simulate the input-output relation in systems similar to the eye of Limulus, a model with backward inhibition must be constructed. Two important properties of backward inhibition not shared by forward inhibition are: (1) Inhibition in a receptor unit has an influence upon its excitation, as well as upon its ability to inhibit other units (Disinhibition). (2) The range of interaction between sensory units is not necessarily the same as the range of direct cross connections. It is shown in this paper, that also forward inhibition may possess these two properties, provided that it is repeated on subsequent levels. Some properties of systems with backward and forward inhibition are studied and compared in models consisting of three units. The input-output relation for large systems with backward inhibition was calculated under special assumptions concerning the inhibitory coefficients. If the inhibitory coefficients in a system with backward inhibition decrease like a power series, as a function of the distance between receptor units, only neighboring receptors have an effect upon each other. That is, in an equivalent system with forward inhibition the inhibitory interaction is confined to neighbouring receptors. Conversely, when backward inhibition exists only between neighbouring receptors, the inhibitory coefficients in an equivalent system with forward inhibition are described, as a function of the distance between the receptor units, by a power series with alternating sign. 相似文献
3.
Spatial summation of inhibitory influences in the eye of Limulus,and the mutual interaction of receptor units
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The inhibitory influences exerted mutually among the receptor units (ommatidia) of the lateral eye of Limulus are additive. If two groups of receptors are illuminated together the total inhibition they exert on a "test receptor" near them (decrease in the frequency of its nerve impulse discharge in response to light) depends on the combined inhibitory influences exerted by the two groups. If the two groups are widely separated in the eye, their total inhibitory effect on the test receptor equals the sum of the inhibitory effects they each produce separately. If they are close enough together to interact, their effect when acting together is usually less than the sum of their separate effects, since each group inhibits the activity of the other and hence reduces its inhibitory influence. However, the test receptor, or a small group illuminated with it, may interact with the two groups and affect the net inhibitory action. A variety of quantitative effects have been observed for different configurations of three such groups of receptors. The activity of a population of n interacting elements is described by a set of n simultaneous equations, linear in the frequencies of the receptor elements involved. Applied to three interacting receptors or receptor groups equations are derived that account quantitatively for the variety of effects observed in the various experimental configurations of retinal illumination used. 相似文献
4.
In the compound lateral eye of Limulus each ommatidium functions as a single receptor unit in the discharge of impulses in the optic nerve. Impulses originate in the eccentric cell of each ommatidium and are conducted in its axon, which runs without interruption through an extensive plexus of nerve fibers to become a fiber of the optic nerve. The plexus makes interconnections among the ommatidia, but its exact organization is not understood. The ability of an ommatidium to discharge impulses in the axon of its eccentric cell is reduced by illumination of other ommatidia in its neighborhood: the threshold to light is raised, the number of impulses discharged in response to a suprathreshold flash of light is diminished, and the frequency with which impulses are discharged during steady illumination is decreased. Also, the activity that can be elicited under certain conditions when an ommatidium is in darkness can be inhibited similarly. There is no evidence for the spread of excitatory influences in the eye of Limulus. The inhibitory influence exerted upon an ommatidium that is discharging impulses at a steady rate begins, shortly after the onset of the illumination on neighboring ommatidia, with a sudden deep minimum in the frequency of discharge. After partial recovery, the frequency is maintained at a depressed level until the illumination on the neighboring receptors is turned off, following which there is prompt, though not instantaneous recovery to the original frequency. The inhibition is exerted directly upon the sensitive structure within the ommatidium: it has been observed when the impulses were recorded by a microelectrode thrust into an ommatidium, as well as when they were recorded more proximally in single fibers dissected from the optic nerve. Receptor units of the eye often inhibit one another mutually. This has been observed by recording the activity of two optic nerve fibers simultaneously. The mediation of the inhibitory influence appears to depend upon the integrity of nervous interconnections in the plexus: cutting the lateral connections to an ommatidium abolishes the inhibition exerted upon it. The nature of the influence that is mediated by the plexus and the mechanism whereby it exerts its inhibitory action on the receptor units are not known. The depression of the frequency of the discharge of nerve impulses from an ommatidium increases approximately linearly with the logarithm of the intensity of illumination on receptors in its vicinity. Inhibition of the discharge from an ommatidium is greater the larger the area of the eye illuminated in its vicinity. However, equal increments of area become less effective as the total area is increased. The response of an ommatidium is most effectively inhibited by the illumination of ommatidia that are close to it; the effectiveness diminishes with increasing distance, but may extend for several millimeters. Illumination of a fixed region of the eye at constant intensity produces a depression of the frequency of discharge of impulses from a nearby ommatidium that is approximately constant, irrespective of the level of excitation of the ommatidium. The inhibitory interaction in the eye of Limulus is an integrative process that is important in determining the patterns of nervous activity in the visual system. It is analogous to the inhibitory component of the interaction that takes place in the vertebrate retina. Inhibitory interaction results in the exaggeration of differences in sensory activity from different regions of the eye illuminated at different intensities, thus enhancing visual contrast. 相似文献
5.
Electrophysiological basis for the spatial dependence of the inhibitory coupling in the Limulus retina 总被引:1,自引:1,他引:0
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A technique for measuring, with total optical isolation, the inhibition between two individual receptor units in the Limulus lateral eye is described. The extracellular responses of pairs of units were recorded, using light piping microelectrodes. The inhibitory coupling between two units was found to be nonlinear and describable by a simple hyperbolic equation written in terms of saturation rate (S), half saturation (H), and threshold (ft). By plotting reciprocal frequencies, the data could be linearized and compared for different pairs of units. The magnitude of inhibition (in terms of S and H) was found to decrease monotonically as the anatomical distance between receptors increased. An electrical model of the inhibitory system was developed which accounts for many of the properties of the observed inhibitory interactions. Using the equations from the model and the experimental data, it is shown that the "electrical distances" (which are computed in terms of space constants lambda) of the inhibitory synapses from the impulse-generating region of the test unit are directly related to the anatomical distance between receptors. It is also shown that "synaptic strength" is relatively constant with separation. The electrical distances of the inhibitory synapses range from about 0.1lambda to 0.25lambda for adjacent units to greater than 0.5lambda for units seven to nine receptors away. It is concluded that the nonlinear character of the inhibitory coupling is attributable to synaptic effects, and that the decrease of inhibition with distance between receptors is caused primarily by an increase in the electrical distance of the inhibitory synapses from the test unit. 相似文献
6.
Summary The functional properties of the processing of visual information by the complex eye of Limulus was studied. The spatial distribution of activity that results in the optic nerve when the Limulus eye is exposed to a stationary optical pattern depends upon the transfer characteristics of two subsystems: the dioptric apparatus and the nervous interactions comprising the lateral inhibition system. — The transfer characteristic of the dioptric apparatus is determined by the sensitivity distribution function of single ommatidia. This distribution was measured and found to be approximately of Gauss-function type. The sensitivity falls off to 1/e at a distance of one ommatidium; thus the visual fields of adjacent ommatidia strongly overlap. As a consequence of the overlap, amplitudes of the spatial Fourier components, of which the brightness distribution of the optical surround is made up, are more and more reduced with increasing frequency in the intensity distribution on the receptor mosaic. The amplitude of the spatial frequency 1/=0,25 ( in units of interommatidial distance) is reduced to half of the maximum value, which is attained at zero frequency. It is shown that the amplitude frequency characteristic of the sensitivity distribution function has no zeros, which means that no loss of optical information results from overlap of visual fields. Thus the resolving power of the dioptric apparatus is limited only by the number of receptors per unit area. — The transfer characteristic of the lateral inhibition system in the Limulus eye depends on the distribution of the inhibitory coefficients around the individual receptors. This distribution function was determined from excitatory responses in the optic nerve elicited by a spatial light intensity step function on the receptor mosaic. It is found that this distribution is also Gaussian in form, but decays to 1/e at a distance of eight to nine ommatidia along the major axis of the eye. The average value of the inhibitory coefficients between adjacent ommatidia was found to be 0,025. The amplitude frequency response of the inhibitory system is constant for high spatial frequencies down to 1/=0,1 while amplitudes of lower frequency sinusoids are reduced down to nearly half of the maximum value at frequency zero. The amplitude frequency characteristic of the inhibitory system ensures a one to one correspondence between the intensity distribution on the receptor mosaic and the excitation distribution in the optic nerve. The overall transfer characteristic of the eye is derived from the transfer characteristics of the dioptric apparatus and the inhibitory system. This characteristic is of bandpass type with a maximum amplitude response at a frequency of 1/=0,07. The overall transfer characteristic was independently confirmed in a separate experiment. The nature of the overall transfer characteristic shows that the inhibitory system does not exactly correct for the overlap of the visual fields of single ommatidia, which in principal the system could do if the distributions of inhibitory coefficients and ommatidia sensitivity were equal. The overall transfer characteristic of the Limulus eye garantees a one to one correspondence between patterns in the optical surround and excitation distributions in the optic nerve. — The average values of the inhibitory coefficients derived from these experiments are at least a factor ten smaller than those determined directly by other investigators. Possible explanations of this discrepency are discussed. — In a separate chapter the overall transfer characteristic for eyes submerged in water is described. It was found that this characteristic does not differ from that determined in air for the eye region which was investigated in the experiments. This result is explained by two properties of the eye which are dependent on the refractive index of the surround medium and whose influences cancel each other: the visual fields of ommatidia are reduced under water, while the divergence angles between the optical axes of adjacent ommatidia also diminish.
This research was supported in part by the United States Air Force under Grant No. AF-EOAR-62-41 and monitored by the European Office, Office of Aerospace Research. 相似文献
This research was supported in part by the United States Air Force under Grant No. AF-EOAR-62-41 and monitored by the European Office, Office of Aerospace Research. 相似文献
7.
A Nonlinearity in the Inhibitory Interactions in the Lateral Eye of Limulus 总被引:4,自引:4,他引:0
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Receptor units in the eye of the horseshoe crab are more sensitive to lateral inhibition at some levels of excitation than they are at others. As a result, the steady-state inhibition of the response of a given unit is not directly proportional to the response levels of neighboring units. This effect may be represented by the introduction of a nonlinearity in the Hartline-Ratliff system of equations. The nonlinear inhibitory effect appears to increase the operating range of the receptor units. 相似文献
8.
Yunhua Shi Alireza Abdolvahabi Bryan F Shaw 《Protein science : a publication of the Protein Society》2014,23(10):1417-1433
This article utilized “protein charge ladders”—chemical derivatives of proteins with similar structure, but systematically altered net charge—to quantify how missense mutations that cause amyotrophic lateral sclerosis (ALS) affect the net negative charge (Z) of superoxide dismutase-1 (SOD1) as a function of subcellular pH and Zn2+ stoichiometry. Capillary electrophoresis revealed that the net charge of ALS-variant SOD1 can be different in sign and in magnitude—by up to 7.4 units per dimer at lysosomal pH—than values predicted from standard pKa values of amino acids and formal oxidation states of metal ions. At pH 7.4, the G85R, D90A, and G93R substitutions diminished the net negative charge of dimeric SOD1 by up to +2.29 units more than predicted; E100K lowered net charge by less than predicted. The binding of a single Zn2+ to mutant SOD1 lowered its net charge by an additional +2.33 ± 0.01 to +3.18 ± 0.02 units, however, each protein regulated net charge when binding a second, third, or fourth Zn2+ (ΔZ < 0.44 ± 0.07 per additional Zn2+). Both metalated and apo-SOD1 regulated net charge across subcellular pH, without inverting from negative to positive at the theoretical pI. Differential scanning calorimetry, hydrogen-deuterium exchange, and inductively coupled plasma mass spectrometry confirmed that the structure, stability, and metal content of mutant proteins were not significantly affected by lysine acetylation. Measured values of net charge should be used when correlating the biophysical properties of a specific ALS-variant SOD1 protein with its observed aggregation propensity or clinical phenotype. 相似文献
9.
Electrophysiology of the Insect Dorsal Ocellus : III. Responses to flickering light of the dragonfly ocellus 总被引:1,自引:1,他引:0
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Philip Ruck 《The Journal of general physiology》1961,44(3):641-657
The ERG of the dragonfly ocellus has been analyzed into four components, two of which originate in the photoreceptor cells, two in the ocellar nerve fibers (Ruck, 1961 a). Component 1 is a sensory generator potential, component 2 a response of the receptor axons. Component 3 is an inhibitory postsynaptic potential, component 4, a discharge of afferent nerve impulses in ocellar nerve fibers. Responses to flickering light are examined in terms of this analytic scheme. It has been found that the generator potential can respond to higher rates of flicker—up to 220/sec.—than can the receptor axon responses, the postsynaptic potential, or the ocellar nerve impulses. The maximum flicker fusion frequency as measured by fusion of the ERG is that of the sensory generator potential itself. 相似文献
10.
Studies on the Distribution of Factor I and Acetylcholine in Crustacean Peripheral Nerve 总被引:2,自引:1,他引:1
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Extracts of whole nerve (chelipeds of Cancer magister) cause inhibition of impulse generation of the crayfish stretch receptor preparation, similar to that produced by gamma-aminobutyric acid (GABA). This is not found with extracts containing only sensory or sensory and motor fibers. Extracts of inhibitory fibers inhibit the stretch receptor discharge—indicating an inhibitory action equivalent to that of up to 30,000 micrograms of GABA per gm. wet weight of inhibitor fiber. This high value is taken as an indication that the inhibitory substance in crab inhibitory fibers is not identical with gamma-aminobutyric acid. Whole nerves were found to contain 1.7 to 6.7 µg. acetylcholine per gm. nerve tissue (clam ventricle and frog rectus abdominis muscle). No acetylcholine could be detected in extracts of motor and inhibitory fibers. The acetylcholine content of sensory fibers can account for the acetylcholine activity of whole nerve extract. It is concluded that the factor I of crustacean nerve is an exclusive property of the inhibitory fibers. The results support the assumption that factor I is the transmitter substance of inhibitory neurons in these animals. The absence of acetylcholine in motor fibers indicates that this substance does not function as a transmitter of motor impulses in Crustacea, and explains the previously observed failure of the substance to elicit motor responses in these animals. The function of acetylcholine in sensory fibers is not yet clarified. 相似文献
11.
Reversal of Photoreceptor Polarity Recorded during the Graded Receptor Potential Response to Light in the Eye of Limulus 总被引:5,自引:0,他引:5
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R. M. Benolken 《Biophysical journal》1961,1(7):551-564
Intracellular electrodes were inserted into single photoreceptor units of the excised lateral eye of Limulus, and preparations were selected from which graded receptor potentials of relatively large amplitude could be recorded in response to light stimuli. The experimental data indicated that the graded receptor potential does not arise solely from a collapse of the resting membrane potential of the sensory cells of the eye, since a reversal of polarity of the photoreceptor unit could be demonstrated when the eye was stimulated by light. In the recovery period following stimulation, characteristic changes in the so-called resting potential were recorded. It is suggested that these changes in the so-called resting membrane potential are electrical signs of recovery processes occurring in the photoreceptor, because the potential changes were recorded when the eye was in darkness and because the magnitudes of the potential changes were a predictable function of the intensity and duration parameters of the preceding light stimulus. 相似文献
12.
Alireza Abdolvahabi Yunhua Shi Nicholas?R. Rhodes Nathan?P. Cook Angel?A. Martí Bryan?F. Shaw 《Biophysical journal》2015,108(5):1199-1212
Although the magnitude of a protein’s net charge (Z) can control its rate of self-assembly into amyloid, and its interactions with cellular membranes, the net charge of a protein is not viewed as a druggable parameter. This article demonstrates that aspirin (the quintessential acylating pharmacon) can inhibit the amyloidogenesis of superoxide dismutase (SOD1) by increasing the intrinsic net negative charge of the polypeptide, i.e., by acetylation (neutralization) of multiple lysines. The protective effects of acetylation were diminished (but not abolished) in 100 mM NaCl and were statistically significant: a total of 432 thioflavin-T amyloid assays were performed for all studied proteins. The acetylation of as few as three lysines by aspirin in A4V apo-SOD1—a variant that causes familial amyotrophic lateral sclerosis (ALS)—delayed amyloid nucleation by 38% and slowed amyloid propagation by twofold. Lysines in wild-type- and ALS-variant apo-SOD1 could also be peracetylated with aspirin after fibrillization, resulting in supercharged fibrils, with increases in formal net charge of ∼2 million units. Peracetylated SOD1 amyloid defibrillized at temperatures below unacetylated fibrils, and below the melting temperature of native Cu2,Zn2-SOD1 (e.g., fibril Tm = 84.49°C for acetylated D90A apo-SOD1 fibrils). Targeting the net charge of native or misfolded proteins with small molecules—analogous to how an enzyme’s Km or Vmax are medicinally targeted—holds promise as a strategy in the design of therapies for diseases linked to protein self-assembly. 相似文献
13.
In mosaic fate mapping the fraction of mosaics in which two structures are of different genotype is calculated. This frequency of separation has been called a "distance" and the units of this distance are called "sturts". The fundamental assumption of fate mapping is that the frequency of separation increases continuously with the actual distance between the anlage for these structures on the blastoderm. This paper shows that the frequency of separation does not increase beyond a certain value.—For the current theory to work as proposed, each mosaic animal must be half mutant and half normal. This is rarely the case in collections of mosaics. It has been thought that if some flies are less than half mutant and others more than half, these two types would introduce compensating errors in mapping distance. We show that this is not true and describe the nature of the errors introduced. It is probable that these errors are the main reason that mapping distances reported from different sets of mosaics have not been reproducible. This paper presents methods for the proper handling of data from mosaics with different amounts of mutant tissue.—We prove here that for mosaics with an arbitrary fraction of mutant tissue (m), the largest frequency of separation that can occur is 2m. We prove that sturts underestimate actual distance on the blastoderm by a factor of r/m, where r is the radius of the mutant patch, and that sturts give no information on distances greater than 2r. This, and not double crossing over, is the reason for the nonadditivity of sturts and the shrinking of large distances in sturt measures. Sturtoids overestimate distances by a factor of 1/(2r) and also give no information on distances over 2r. This paper gives formulae for correctly estimating distance when using a collection of mosaics with varying amounts of mutant tissue. We also describe the nature of the errors introduced by convoluted or elongate mosaic boundaries and by multiple mosaic patches. 相似文献
14.
The response to light of one ommatidium is reduced or suppressed by simultaneous illumination of neighboring ommatidia. The mechanism of this lateral inhibition may be chemical synaptic transmission, based on the physiological findings of a number of investigators and on the following evidence. The fine structure of the neuropil of the lateral plexus exhibits numerous clear vesicles (ca. 400 A), dense-core vesicles (ca. 700–1400 A), Golgi regions, and other morphological features of neurochemical synapses. The indolealkylamine, serotonin (5-HT), even in nanomolar concentrations, has a potent inhibitory action. An initial, potent inhibitory dose of 5-HT produces a long lasting densensitization to subsequent doses. The desensitization affects lateral inhibition evoked by light stimulation of neighboring receptors, i.e. crossed-desensitization. Eye tissue extracts contain 5-HT and melatonin (MLT) at a level greater than 1 µg/g wet tissue and perhaps as high as 20–30 µg/g, as determined by two-dimensional thin-layer chromatography (TLC) and o-phthaldialdehyde fluorescence assay techniques. Subcellular fractionation on sucrose gradient indicates a peak in 5-HT and MLT content associated with an intermediate density fraction. 5-HT may be an inhibitory transmitter for lateral inhibition. One pathway for metabolism of 5-HT in the lateral eye may be via N-acetylserotonin and melatonin. 相似文献
15.
The inhibition that is exerted mutually among the receptor units (ommatidia) in the lateral eye of Limulus has been analyzed by recording oscillographically the discharge of nerve impulses in single optic nerve fibers. The discharges from two ommatidia were recorded simultaneously by connecting the bundles containing their optic nerve fibers to separate amplifiers and recording systems. Ommatidia were chosen that were separated by no more than a few millimeters in the eye; they were illuminated independently by separate optical systems. The frequency of the maintained discharge of impulses from each of two ommatidia illuminated steadily is lower when both are illuminated together than when each is illuminated by itself. When only two ommatidia are illuminated, the magnitude of the inhibition of each one depends only on the degree of activity of the other; the activity of each, in turn, is the resultant of the excitation from its respective light stimulus and the inhibition exerted on it by the other. When additional receptors are illuminated in the vicinity of an interacting pair too far from one ommatidium to affect it directly, but near enough to the second to inhibit it, the frequency of discharge of the first increases as it is partially released from the inhibition exerted on it by the second (disinhibition). Disinhibition simulates facilitation; it is an example of indirect effects of interaction taking place over greater distances in the eye than are covered by direct inhibitory interconnections. When only two interacting ommatidia are illuminated, the inhibition exerted on each (decrease of its frequency of discharge) is a linear function of the degree of activity (frequency of discharge) of the other. Below a certain frequency (often different for different receptors) no inhibition is exerted by a receptor. Above this threshold, the rate of increase of inhibition of one receptor with increasing frequency of discharge of the other is constant, and may be at least as high as 0.2 impulse inhibited in one receptor per impulse discharged by the other. For a given pair of interacting receptors, the inhibitory coefficients are not always the same in the two directions of action. The responses to steady illumination of two receptor units that inhibit each other mutually are described quantitatively by two simultaneous linear equations that express concisely all the features discussed above. These equations may be extended and their number supplemented to describe the responses of more than two interacting elements. 相似文献
16.
What is the relationship between film viewers’ eye movements and their film comprehension? Typical Hollywood movies induce strong attentional synchrony—most viewers look at the same things at the same time. Thus, we asked whether film viewers’ eye movements would differ based on their understanding—the mental model hypothesis—or whether any such differences would be overwhelmed by viewers’ attentional synchrony—the tyranny of film hypothesis. To investigate this question, we manipulated the presence/absence of prior film context and measured resulting differences in film comprehension and eye movements. Viewers watched a 12-second James Bond movie clip, ending just as a critical predictive inference should be drawn that Bond’s nemesis, “Jaws,” would fall from the sky onto a circus tent. The No-context condition saw only the 12-second clip, but the Context condition also saw the preceding 2.5 minutes of the movie before seeing the critical 12-second portion. Importantly, the Context condition viewers were more likely to draw the critical inference and were more likely to perceive coherence across the entire 6 shot sequence (as shown by event segmentation), indicating greater comprehension. Viewers’ eye movements showed strong attentional synchrony in both conditions as compared to a chance level baseline, but smaller differences between conditions. Specifically, the Context condition viewers showed slightly, but significantly, greater attentional synchrony and lower cognitive load (as shown by fixation probability) during the critical first circus tent shot. Thus, overall, the results were more consistent with the tyranny of film hypothesis than the mental model hypothesis. These results suggest the need for a theory that encompasses processes from the perception to the comprehension of film. 相似文献
17.
Jang Hoon Kim Chong Woon Cho Mok Hur Woo Tae Park Youn-Ho Moon Sung-Cheol Koo Yun-Chan Hur Jong Seong Kang Ik Soo Lee 《Current issues in molecular biology》2022,44(9):4282
The quaternary isoquinoline alkaloids of palmatine (1), berberine (2), and jatrorrhizine (3) were evaluated in terms of their ability to inhibit soluble epoxide hydrolase (sEH). They had similar inhibitory activities, with IC50 values of 29.6 ± 0.5, 33.4 ± 0.8, and 27.3 ± 0.4 μM, respectively. Their respective Ki values of 26.9, 46.8, and 44.5 μM—determined by enzyme kinetics—indicated that they inhibited the catalytic reaction by binding noncompetitively with sEH. The application of computational chemistry to the in vitro results revealed the site of the receptor to which the ligand would likely bind. Accordingly, three alkaloids were identified as having a suitable basic skeleton for lead compound development of sEH inhibitors. 相似文献
18.
Rajprasad Loganathan Charles D Little Pranav Joshi Michael B Filla Tracey J Cheuvront Rusty Lansford Brenda J Rongish 《Organogenesis》2014,10(4):350-364
The tissue scale deformations (≥1mm) required to form an amniote embryo are poorly understood. Here, we studied ∼400 μm-sized explant units from gastrulating quail embryos. The explants deformed in a reproducible manner when grown using a novel vitelline membrane-based culture method. Time-lapse recordings of latent embryonic motion patterns were analyzed after disk-shaped tissue explants were excised from three specific regions near the primitive streak: 1) anterolateral epiblast, 2) posterolateral epiblast, and 3) the avian organizer (Hensen''s node). The explants were cultured for 8 hours—an interval equivalent to gastrulation. Both the anterolateral and the posterolateral epiblastic explants engaged in concentric radial/centrifugal tissue expansion. In sharp contrast, Hensen''s node explants displayed Cartesian-like, elongated, bipolar deformations—a pattern reminiscent of axis elongation. Time-lapse analysis of explant tissue motion patterns indicated that both cellular motility and extracellular matrix fiber (tissue) remodeling take place during the observed morphogenetic deformations. As expected, treatment of tissue explants with a selective Rho-Kinase (p160ROCK) signaling inhibitor, Y27632, completely arrested all morphogenetic movements. Microsurgical experiments revealed that lateral epiblastic tissue was dispensable for the generation of an elongated midline axis— provided that an intact organizer (node) is present. Our computational analyses suggest the possibility of delineating tissue-scale morphogenetic movements at anatomically discrete locations in the embryo. Further, tissue deformation patterns, as well as the mechanical state of the tissue, require normal actomyosin function. We conclude that amniote embryos contain tissue-scale, regionalized morphogenetic motion generators, which can be assessed using our novel computational time-lapse imaging approach. These data and future studies—using explants excised from overlapping anatomical positions—will contribute to understanding the emergent tissue flow that shapes the amniote embryo. 相似文献
19.
Two independent types of lateral inhibition were distinguished in experiments on the frog eye in which the effects of pharmacological agents on the electroretinogram were studied: proximal or picrotoxin-sensitive, and distal or strychnine-sensitive. Distal lateral inhibition (at distances up to 1.5 mm) is the familiar type already well investigated and based on a spike mechanism of transmission of the inhibitory signal. The proximal (up to 400 µ) picrotoxin-sensitive inhibition has a different mechanism of transmission, not dependent on spikes. The localization of the two types of lateral inhibition in the synaptic layers of the frog retina is discussed.Institute for Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 13, No. 5, pp. 549–555, September–October, 1981. 相似文献
20.
In P. transvaalicus nymphs, 5 pairs of lateral ocelli each composed of a corneal lens, R-cell units forming a latticed rhabdom, arhabdomeric cells and pigment cells are present. In addition, we found a pair of unpigmented accessory sense organs situated ventroposteriorly to the lateral ocelli in prenymphs as well as in first nymphs. They are composed of primary, rhabdomeric sensory cells, and we infer that they represent a second type of lateral eye. They also comprise sensory units, but lenses and screening pigment are lacking. Their position and cellular architecture corresponds well with that of the “rudimentary” lateral eye of the xiphosuran, Limulus. The occurrence of a bipartite lateral visual system in Chelicerata and Arthropoda is discussed. 相似文献