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1.
Abstract

Three monoclonal antibodies were used to examine with immunocytochemistry the distribution of the glycine receptors and the related 93kd polypeptide in the adult goldfish brain (Carassius auratus). One immunoglobulin recognizes the 48kd strychnine-binding subunit of the receptor and the two others bind to the peripheral 93kd polypeptide which is coupled to the receptor molecules. Immunofluorescent spots were visualised with all three antibodies on the somatic and dendritic membrane of the cells.

A differential intensity of immunofluorescence was detected in the three different brain regions examined: the brainstem, the cerebellum and the telencephalon. For both proteins, the highest fluorescence was observed in the brainstem, particularly on reticular and vestibular neurons. In the cerebellum both the density and the intensity of labelling was low. At the level of the Mauthner cell, an identified bulbar command neuron, the distribution of glycinergic receptors was identical with that of the 93kd polypeptide. Both subunits were visualized on the somatic and dendritic membrane up to their extremities.

These proteins appear to be colocalized in neurons other than the Mauthner cell, since they are always co-expressed in the same brain region. Their distributions are comparable with that observed in the mouse and rat nervous system as reported from autoradiographic localization of [3H] strychnine binding.  相似文献   

2.
PurposeWithin the SYRMA-CT collaboration based at the ELETTRA synchrotron radiation (SR) facility the authors investigated the imaging performance of the phase-contrast computed tomography (CT) system dedicated to monochromatic in vivo 3D imaging of the female breast, for breast cancer diagnosis.MethodsTest objects were imaged at 38 keV using monochromatic SR and a high-resolution CdTe photon-counting detector. Signal and noise performance were evaluated using modulation transfer function (MTF) and noise power spectrum. The analysis was performed on the images obtained with the application of a phase retrieval algorithm as well as on those obtained without phase retrieval. The contrast to noise ratio (CNR) and the capability of detecting test microcalcification clusters and soft masses were investigated.ResultsFor a voxel size of (60 μm)3, images without phase retrieval showed higher spatial resolution (6.7 mm−1 at 10% MTF) than corresponding images with phase retrieval (2.5 mm−1). Phase retrieval produced a reduction of the noise level and an increase of the CNR by more than one order of magnitude, compared to raw phase-contrast images. Microcalcifications with a diameter down to 130 μm could be detected in both types of images.ConclusionsThe investigation on test objects indicates that breast CT with a monochromatic SR source is technically feasible in terms of spatial resolution, image noise and contrast, for in vivo 3D imaging with a dose comparable to that of two-view mammography. Images obtained with the phase retrieval algorithm showed the best performance in the trade-off between spatial resolution and image noise.  相似文献   

3.
PurposeTo investigate the dose saving potential of direct-converting CdTe photon-counting detector technology for dedicated breast CT.Materials and methodsWe analyzed the modulation transfer function (MTF), the noise power spectrum (NPS) and the detective quantum efficiency (DQE) of two detector technologies, suitable for breast CT (BCT): a flat-panel energy-integrating detector with a 70 μm and a 208 μm thick gadolinium oxysulfide (GOS) and a 150 μm thick cesium iodide (CsI) scintillator and a photon-counting detector with a 1000 μm thick CdTe sensor.ResultsThe measurements for GOS scintillator thicknesses of 70 μm and 208 μm delivered 10% pre-sampled MTF values of 6.6 mm−1 and 3.2 mm−1, and DQE(0) values of 23% and 61%. The 10% pre-sampled MTF value for the 150 μm thick CsI scintillator 6.9 mm−1, and the DQE(0) value was 49%. The CdTe sensor reached a 10% pre-sampled MTF value of 8.5 mm−1 and a DQE(0) value of 85%.ConclusionThe photon-counting CdTe detector technology allows for significant dose reduction compared to the energy-integrating scintillation detector technology used in BCT today. Our comparative evaluation indicates that a high potential dose saving may be possible for BCT by using CdTe detectors, without loss of spatial resolution.  相似文献   

4.
Stimulation of the spinal cord of the electric fish Gymnotus carapo, evoked an abrupt increase in the discharge rate of the electric organ. At the maximum of this response, the rate increased an average of 26 ± 11.8%. The duration of the response was 4.9 ± 2.12 s; its latency was 10.4 ± 1.1 ms. Activation of the Mauthner axon played a decisive role in this phenomenon as indicated by the following: (1) recordings from the axon cap of the Mauthner cell demonstrated that the response was evoked if the Mauthner axon was antidromically activated and (2) a response that was similar to that produced by spinal cord stimulation, was elicited by intracellular stimulation of either Mauthner cell. Stimulation of the eighth nerve could also increase the discharge rate of the electric organ. The effect was greater if a Mauthner cell action potential was elicited. The findings described in the present report, indicate the existence of a functional connection between the Mauthner cell and the electromotor system in Gymnotus carapo. This connection may function to enhance the electrolocative sampling of the environment during Mauthner-cell mediated behaviors. This is a novel function for the Mauthner cell.Abbreviations EHP extrinsic hyperpolarizing potential - EOD electric organ discharge - M-AIR Mauthner initiated abrupt increase in rate - M-cell Mauthner cell - M-axon Mauthner axon - PM pacemaker nucleus - PM-cell pacemaker cell - PPn prepacemaker nucleus - SPPn sublemniscal prepacemaker nucleus  相似文献   

5.
《Genomics》2022,114(4):110424
ObjectiveSerine hydroxymethyltransferase 2 (SHMT2) is the first rate-limiting enzyme for serine/glycine biosynthesis and one carbon metabolism. Here, we explore the underlying mechanism of how SHMT2 functions in renal cell carcinoma (RCC) initiation.MethodsIn this study, SHMT2 expression was assessed in RCC tissues. In vitro experiments were performed to investigate the functional role of SHMT2. The detailed mechanisms of SHMT2-mediated PPAT were addressed.ResultsIncreased SHMT2 facilitated RCC cell proliferation by inducing the G1/S phase transition. And SHMT2 promoted the expression of PPAT. Mechanism dissection revealed that SHMT2 enhanced the m6A modification through the endogenous methyl donor SAM mediated by SHMT2 via serine/glycine one carbon metabolic networks. SHMT2-catalyzed serine/glycine conversion regulated PPAT expression in an m6A-IGF2BP2-dependent manner. SHMT2 promoted RCC cell proliferation by upregulating PPAT expression.ConclusionsSHMT2 promotes RCC tumorigenesis by increasing PPAT expression. Thus, SHMT2 may be a novel potential therapeutic target for RCC.  相似文献   

6.
The development of adenosine A2A receptor antagonists has received much interest in recent years for the treatment of neurodegenerative diseases. Based on docking studies, a new series of 2-arylbenzoxazoles has been identified as potential A2AR antagonists. Structure-affinity relationship was investigated in position 2, 5 and 6 of the benzoxazole heterocycle leading to compounds with a micromolar affinity towards the A2A receptor. Compound F1, with an affinity of 1?μm, presented good absorption, distribution, metabolism and excretion properties with an excellent aqueous solubility (184?μm) without being cytotoxic at 100?μm. This compound, along with low-molecular weight compound D1 (Ki?=?10?μm), can be easily modulated and thus considered as relevant starting points for further hit-to-lead optimisation.  相似文献   

7.
The overall surface disposition of receptors for the neurotransmitter glycine was examined in situ on the teleost Mauthner cell. For this purpose, a monoclonal antibody specific for the glycine receptor was used in immunofluorescence experiments in association with the technique of confocal microscopy. Previous work had shown that on the Mauthner cell and other neurons, receptors for this transmitter are concentrated in discrete microdomains apposed to single presynaptic terminals. We now report that the size and the shape of these clusters depend on their cellular location, that is, their area increases regularly from the soma to the tip of the dendrites. Conversely, the number of clusters per unit area declines so that the final proportion of immunoreactive membrane remains constant at any portion of the cell. These results raise the question of the functional consequences of such an organized subcellular distribution of receptors.  相似文献   

8.
BackgroundProton magnetic resonance spectroscopy (1H-MRS) clinical studies of patients with schizophrenia document prefrontal N-acetylaspartate (NAA) reductions, suggesting an effect of the disease or of antipsychotic medications. We studied in the rat the effect of prolonged exposure to a low-dose of the NMDA glutamate receptor antagonist phencyclidine (PCP) on levels of NAA, glutamate and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia.MethodsTwo groups of ten rats each were treated with PCP (2.58 mg/kg/day) or vehicle and were sacrificed after 1 month treatment. Concentrations of neurochemicals were determined with high resolution magic angle (HR-MAS) 1H-MRS at 11.7 T in ex vivo punch biopsies from the medial frontal and cingulate cortex, striatum, nucleus accumbens, amygdala and ventral hippocampus.ResultsPCP treatment reduced NAA, glutamate, glycine, aspartate, creatine, lactate and GABA in medial frontal cortex. In the nucleus accumbens, PCP reduced levels of NAA, aspartate and glycine; similarly aspartate and glycine were reduced in the striatum. Finally the amygdala and hippocampus had elevations in glutamine and choline, respectively.ConclusionsLow-dose PCP in rats models prefrontal NAA and glutamate reductions documented in chronically-ill schizophrenia patients. Chronic glutamate NMDA receptor blockade in rats replicates an endophenotype in schizophrenia and may contribute to the prefrontal hypometabolic state in schizophrenia.  相似文献   

9.
Abstract

In this work, we describe a process for production of a Pichia pastoris strain which overproduces large quantities of the human glycine receptor. Subsequent purification yielded functional, uniform protein with expression yields of up to 5 mg per liter cell culture. As the wild-type protein is prone to proteolytic degradation, the labile sites were removed by mutagenesis resulting in an intracellular loop 2 deletion mutant with N-terminal modifications. This variant of the receptor is both stable during purification and storage on ice for up to a week as a complex with an antagonist. The quality of the protein is suitable for biophysical characterization and structural studies. The interaction of the agonist glycine and the antagonist strychnine with purified protein was analyzed by isothermal titration calorimetry. Strychnine binding is driven enthalpically with a KD of 138 ± 55 nM, a ΔH of ?9708 ± 1195 cal/mol and a ΔS of ?1.0 ± 4.1 cal/mol/K, whereas glycine binding is driven by entropy with a KD of 3.2 ± 0.8 μM, a ΔH of ?2228 ± 1012 cal/mol and ΔS of 17.7 ± 2.8 cal/mol/K. Strychnine and glycine binding is competitive with a stoichiometry of one ligand molecule to one pentameric glycine receptor.  相似文献   

10.
PurposeThis study aimed to assess the noise characteristics of ultra-high-resolution computed tomography (UHRCT) with deep learning-based reconstruction (DLR).MethodsTwo different diameters of water phantom were scanned with three different resolution acquisition modes. Images were reconstructed by filtered back projection (FBP), hybrid iterative reconstruction (hybrid-IR), and DLR. Image noise analysis was performed with noise magnitude, peak frequency (fp) of the noise power spectrum (NPS), and the square root of the area under the curve (√AUCNPS) for the NPS curve.ResultsThe noise magnitude was up to 3.30 times higher for the FBP acquired in SHR mode than that for the NR mode.The fp values of the FBP were 0.20–0.21, 0.34–0.36, and 0.34–0.37 cycles/mm for normal resolution (NR), high resolution (HR), and super high resolution (SHR) mode, respectively. The fp of hybrid-IR was 0.16–0.19, 0.21–0.26, and 0.23–0.26 cycles/mm for NR, HR, and SHR mode, respectively. The fp of DLR was 0.21–0.32 and 0.22–0.33 cycles/mm for HR and SHR mode, respectively.√AUCNPS showed that the highest value in FBP images of the SHR mode was up to 1.89 times that of the NR mode. DLR in the HR and SHR modes showed high noise reduction while suppressing fp shift with respect to FBP.ConclusionsThe new DLR algorithm could be a solution to the noise increase due to the high-definition detector elements and the small reconstruction matrix element size.  相似文献   

11.
目的 胃癌(GC)严重影响人类的健康生活,研究表明其与丝氨酸/甘氨酸代谢密切相关。丝氨酸/甘氨酸代谢对于肿瘤细胞的增殖能力具有重要影响。本文的研究目的是探究丝氨酸/甘氨酸代谢能够影响胃癌细胞增殖能力的分子机制。方法 本文通过一种基于随机和非梯度系统的势能景观所建立的大型代谢网络动力学建模方法,构建了一个稳定的胃癌细胞代谢动力学模型。基于对模型的调控,定量分析丝氨酸/甘氨酸代谢影响胃癌细胞增殖的动力学机制。对一般代谢网络动力学方程添加随机噪声,通过随机动力学分解得到代谢网络参数空间的李雅普诺夫(Lyapunov)函数。进一步减少与随机波动相关的Lyapunov函数变化,从而得到稳定的代谢网络。结果 在动力学参数不足的情况下,成功构建了胃癌细胞代谢网络的动力学模型。当胞外丝氨酸可用时,模型优先消耗丝氨酸;当甘氨酸生成丝氨酸的速率增加时,模型显著上调生成S-腺苷甲硫氨酸(SAM)和S-腺苷同型半胱氨酸(SAH)的稳态通量。结论 本文证明了胃癌细胞对于丝氨酸的优先摄取以及丝氨酸/甘氨酸转化速率对SAM生成的重要作用,其可能通过调节细胞甲基化进程影响胃癌细胞的增殖能力,为靶向丝氨酸/甘氨酸代谢的癌症治疗提供了新的思路和方向。  相似文献   

12.
Abstract

The Xenopus oocyte translation system has been developed for the recognition of receptor messenger-RNA molecules. Observations with the nicotinic acetylcholine, GABA, glycine, glutamate and serotonin receptors show that the mRNAs coding for their subunits can be faithfully translated in the oocyte and the products processed, glycosylated, assembled to a receptor structure, inserted correctly in the cell membrane and organised to form the functional ion channel. The specific regulatory interactions between different sites on one receptor, as exemplified in the GABAA receptor, are established in this process. This system is of value for the detection of mRNAs for receptor gene cloning and for the study of receptor assembly and of the expression of multiple receptor genes. The receptor ion channels formed can also be studied in their own right in a highly accessible and controlled situation.  相似文献   

13.
Chen SH  Tsai YJ  Wang HY  Lin CT  Li SF  Lue JH 《Life sciences》2012,90(7-8):278-288
AimsThis study aimed to investigate temporal changes in glycine and its receptor expressions in cuneate neurons after median nerve transection (MNT), and the effects of glycine on neuropeptide Y (NPY) release and c-Fos expression in the cuneate nucleus (CN).Main methodsImmunohistochemistry methods were used to appraise changes of glycine- and GlyR-like immunoreactive (LI) neurons in the CN after MNT. The alterations in NPY and c-Fos expressions were used to assess the effects of saline, glycine or strychnine treatment. The CatWalk method was used to assess the efficiency of glycine treatment on the neuropathic signs of rats with MNT.Key findingsApproximately half of GlyR-LI neurons were fluorogold-labeled cuneothalamic projection neurons in the CN. Following MNT, the number of GlyR-LI neurons significantly decreased in the injured side of CN at 2 and 4 weeks, but the number of glycine-LI neurons remained unchanged. Four weeks after MNT given with electrical stimulation, strychnine significantly decreased the NPY reduction level in the stimulated side CN compared to that of the saline group. However, numbers of c-Fos-LI neurons in the glycine and strychnine groups were both significantly less than that in the saline group. But the paw print width and area in CatWalk analysis showed only a moderate recovery.SignificanceWe conjecture that glycine increases glycine-mediated postsynaptic inhibition of cuneate neurons, and also blocks GABAergic neurons containing GlyRs which mediate presynaptic inhibition causing temperate NPY release. Consequently, the compromise results showed a weak reduction in c-Fos expression and a slight amelioration of neuropathic behaviors.  相似文献   

14.
PurposeTo assess the quality of images obtained on a dual energy computed tomography (CT) scanner.MethodsImage quality was assessed on a 64 detector-row fast kVp-switching dual energy CT scanner (Revolution GSI, GE Medical Systems). The Catphan phantom and a low contrast resolution phantom were employed. Acquisitions were performed at eight different radiation dose levels that ranged from 9 mGy to 32 mGy. Virtual monochromatic spectral images (VMI) were reconstructed in the 40–140 keV range using all available kernels and iterative reconstruction (IR) at four different blending levels. Modulation Transfer Function (MTF) curves, image noise, image contrast, noise power spectrum and contrast to noise ratio were assessed.ResultsIn-plane spatial resolution at the 10% of the MTF curve was 0.60 mm−1. In-plane spatial resolution was not modified with VMI energy and IR blending level. Image noise was reduced from 16.6 at 9 mGy to 6.7 at 32 mGy, while peak frequency remained within 0.14 ± 0.01 mm−1. Image noise was reduced from 14.3 at IR 10% to 11.5 at IR 50% at a constant peak frequency. The lowest image noise and maximum peak frequency were recorded at 70 keV.ConclusionsOur results have shown how objective image quality is varied when different levels of radiation dose and different settings in IR are applied. These results provide CT operators an in depth understanding of the imaging performance characteristics in dual energy CT.  相似文献   

15.
PurposeHybrid iterative reconstruction (IR) is useful to reduce noise in computed tomography (CT) images. However, it often decreases the spatial resolution. The ability of high spatial resolution kernels (harder kernels) to compensate for the decrease in the spatial resolution of hybrid IRs was investigated.MethodsAn elliptic cylindrical phantom simulating an adult abdomen was used. Two types of rod-shaped objects with ~330 and ~130 HU were inserted to simulate contrasts of arteries in CT angiography. Two multi-slice CT systems were used to scan the phantoms with 120 kVp and scan doses of 20 and 10 mGy. The task transfer functions (TTFs) were measured from the circular edges of the rod images. The noise power spectrum (NPS) was measured from the images of the water-only section. The CT images were reconstructed using a filtered back projection (FBP) with baseline kernels and two levels of hybrid IRs with harder kernels. The profiles of the clinical images across the aortic dissection flaps were measured to evaluate actual spatial resolutions.ResultsThe TTF degradation of each hybrid IR was recovered by the harder kernels, whereas the noise reduction effect was retained, for both the 20 and 10 mGy. The profiles of the dissection flaps for the FBP were maintained by using the harder kernels. Even with the best combination of hybrid IR and harder kernel, the noise level at 10 mGy was not reduced to the level of FBP at 20 mGy, suggesting no capability of a 50% dose reduction while maintaining noise.  相似文献   

16.
PurposeThe aim of this work was to introduce a new algorithm for image reconstruction in bone SPECT and to compare its performances with a commercially available standard OSEM and resolution recovery (RR) reconstruction.Materials and methodsThe algorithm was built applying the Lucy-Richardson deconvolution adn logarithmic image processing to the projections. A modification of the coefficients of wavelet decomposition was used to suppress the noise. The comparison with vendor software was performed both in a phantom study, using Signal-to-Noise ratio (SNR), Signal-to-Background ratio (SBR), spatial resolution and in clinical studies, by visual assessment of changes in contrast, spatial resolution and lesion detectability.ResultsA change in the SNR (from −4 to 40%), an increase in the SBR (from 19 to 40%), a minor improvement in spatial resolution and a similar noise level were observed in the phantom study in comparison to the standard OSEM. A decrease in the SNR, a worse spatial resolution, but only a 3 to 13 % lower SBR were achieved in comparison with the vendor supplied RR algorithm. The proposed algorithm creates patient images with better contrast and lesion detectability compared to clinically used OSEM. Compared to RR, more than half of obtained images showed better contrast and nearly half of them have better lesion detectability.ConclusionThe proposed algorithm compares favorably with the standard OSEM. Although less favorable, the comparison with RR and noise suppression algorithms, suggests that it can be used with only a slight decrease in the SBR.  相似文献   

17.
PurposeThis study reports a sensitivity enhancement of gold-coated contact lens-type ocular in vivo dosimeters (CLODs) for low-dose measurements in computed tomography (CT).MethodsMonte Carlo (MC) simulations were conducted to evaluate the dose enhancement from the gold (Au) layers on the CLODs. The human eye and CLODs were modeled, and the X-ray tube voltages were defined as 80, 120, and 140 kVp. The thickness of the Au layer attached to a CLOD ranged from 100 nm to 10 μm. The thickness of the active layer ranged from 20 to 140 μm. The dose ratio between the active layer of the Au-coated CLOD and a CLOD without a layer, i.e., the dose enhancement factor (DEF), was calculated.ResultsThe DEFs of the first 20-μm thick active layer of the 5-μm thick Au-coated CLOD were 18.4, 19.7, 20.2 at 80, 120, and 140 kVp, respectively. The DEFs decreased as the thickness of the active layer increased. The DEFs of 100-nm to 5-μm thick Au layers increased from 1.7 to 5.4 for 120-kVp X-ray tube voltage when the thickness of the active layer was 140 μm.ConclusionsThe MC results presented a higher sensitivity of Au-coated CLODs (∼20-times higher than that of CLODs without a gold layer). Au-coated CLODs can be applied to an evaluation of very low doses (a few cGy) delivered to patients during CT imaging.  相似文献   

18.
The time of the last DNA replication of the Mauthner's neuron precursor cell has been investigated using radioautography. Embryos of Xenopus laevis were labeled at different stages of early development by single microinjections of tritiated thymidine. Labeling times were designed to cover the entire period of development between gastrula and hatching stages. The embryos were fixed at later stages (41 to 44, according to Nieuwkoop and Faber, 1967), when the Mauthner neuron can be readily distinguished by its characteristically large size and large nucleolus.Mauthner neurons of embryos which received tritiated thymidine from stage 10 (beginning of gastrulation) to stage 12 (advanced gastrula, medium yolk plug) were always labeled. Those embryos which received the isotope at or after stage 1212 (advanced gastrula, small yolk plug) were never found labeled. These results imply that the last DNA replication of the cell destined to give rise to the Mauthner neuron occurs during the last gastrula stages. This last DNA replication immediately proceeds the time of the so-called “histogenetic determination” of the Mauthner neuron proposed to correspond to stage 13 (slit blastopore) by Stefanelli (1951).Therefore it appears that the developmental program of the Mauthner neuron involves a remarkably early cessation of DNA replication closely followed by histogenetic determination. This is the earliest known event of this type for a specific, well characterized neuron in the amphibian embryo.  相似文献   

19.
The dragonfly Hemicordulia tau has five spectral classes of photoreceptor which drive five lamina monopolars, m1-m5. The monopolars encode spectral information. Here, spectral coding by m2, m4 and m5 are described. m2 is the most sensitive to dim light. m4 and m5 are less sensitive than m2, and so we call them photopic cells. The effects of selective adaptation of receptor inputs to m4 and m5 are unusual. For example, in m4 adaptation of the green receptor suppresses the UV input, but green sensitivity is unaffected, while green adaptation of m5 increases its green sensitivity. In m5 the dark adapted spectral tuning resembles the 520 nm receptor, but on adaptation to 430 nm light this narrows markedly. Adaptation either of green or of UV receptor input to m2 and m4 modifies the time course of responses both to green and to UV, implying that changes in the time courses of monopolar responses with adaptation state do not directly reflect receptor responses (Fig. 2). Finally, the antagonistic surround of m2 is UV sensitive, and of m4 green sensitive (Fig. 3).Abbreviations LMC large monopolar cell - LVF long visual fibre - rf receptive field - SVF short visual fibre  相似文献   

20.
The cellular structure of two products, an extruded breakfast cereal and a short dough biscuit, was characterized by two different X-ray micro computed tomographic systems. Acquisitions were made by a compact desktop system Skyscan 1174 (Bruker μCT, Belgium) and at the European Synchrotron Radiation Facility (ESRF, beamline ID19, France) at different resolutions (voxel size of 6.5 μm, 7.5 μm, 16.2 μm and 25.8 μm). 3D images were processed for the density, the connectivity index and the granulometry of cells and cell walls. These experiments underlined the importance of the resolution for determination of quantitative measurements such as densities and thicknesses. The median width calculated for the cell walls distribution in the biscuit dropped from 141 to 50 μm when the voxel size changed from 25.8 to 7.5 μm. Images well showed that even though the food products had close values of porosity 0.6 and 0.7 for biscuit and extruded breakfast cereal respectively, their cellular structures were very different. The biscuit had small cells (median value of the distribution varied from 125 to 152 μm, according to resolution) and larger cell walls (50–141 μm) than the extrudate (32–109 μm) which, on the contrary, exhibited very large cells (307–400 μm). Beyond methodological issues, these differences could be clearly attributed to the differences of compositions and processes.  相似文献   

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