Ca 2þ -triggered membrane fusion, the defining step of exocytosis, enables temporal/spatial control over the release of biologically active compounds. The mechanism by which Ca 2þ triggers and modulates native membrane fusion is still poorly understood. As an unbiased approach to investigating this process, the effects of several thiol-reactive reagents on the homotypic fusion of isolated cortical vesicles (a stage-specific preparation for analyses of native Ca 2þ -triggered fusion) have been characterized. Such reagents have been consistently shown to inhibit the Ca 2þ -sensitivity, rate and extent of triggered fusion. However, we recently showed that iodoacetamide can also potentiate the Ca 2þ -sensitivity and rate of release [1]. This implicates two distinct thiol sites in the fusion process -one involved in the ability of vesicles to fuse (extent) and one that modulates fusion efficiency (Ca 2þ -sensitivity and kinetics). Capitalizing on this potentiating effect, we have now identified other fluorescent thiol-reactive reagents with similar effects: treatment with Lucifer yellow iodoacetamide, monobromobimane or dibromobimane resulted in an average leftward shift in EC 50 from 17.251.6mM to 8.951.9mM [Ca 2þ ] free . These fluorescent reagents can be used to enhance fusion and label proteins involved in the Ca 2þ -sensing mechanism. The lipid matrix at or near the fusion site can also modulate the fusion process, specifically via cholesterol-and sphingomyelin-enrichment that is thought to regulate the Ca 2þsensitivity and rate of fusion through spatial organization of critical lipids and proteins [2,3]. Proteins involved in Ca 2þ -sensing are thus likely to be situated within such areas of the membrane. Isolation of fluorescently labeled proteins from cholesterol-enriched vesicle membrane fractions by 2-dimesional electrophoresis is now being used to identify proteins potentially involved in the Ca 2þ -triggering steps of membrane fusion.
The transient relationship between arterial cerebral blood flow (CBF A ) and total cerebral blood volume (CBV T ) was determined in the rat brain. Five rats anesthetized with urethane (1.2 g/kg) were examined under graded hypercapnia conditions (7.5% and 10% CO 2 ventilation). The blood oxygenation level-dependent (BOLD) contrast was determined by a gradient-echo echo-planar imaging (GE-EPI) pulse sequence, and CBV T changes were determined after injection of a monocrystalline iron oxide nanocolloid (MION) contrast agent using an iron dose of 12 mg/kg. The relationship between CBV T and CBF A under transient conditions is similar to the power law under steady-state conditions. In addition, the transient relationship between CBV T and CBF A is region-specific. Voxels with ≥15% BOLD signal changes from hypercapnia (7.5% CO 2 ventilation) have a larger Cerebral blood flow (CBF), cerebral blood volume (CBV), and blood oxygenation level-dependent (BOLD) signal changes can be noninvasively quantified in human (1,2) and animal (3) brains using functional MRI (fMRI) methods, which can be employed to calculate the relative cerebral metabolic rate of oxygen consumption (CMRO 2 ). Recent studies reported that fractional changes in blood flow and oxygen uptake are linearly coupled in a consistent ratio of approximately 2:1 in the human primary visual cortex (V1) during graded stimulation. The most potent stimulus produced CBF and CMRO 2 increases of 48% and 25%, respectively (4). Task-induced neural activity, detected by fMRI, significantly increased oxygen consumption in the brain.These fMRI results conflict with previous results from a PET study that employed 18 F-deoxy-glucose, in which neural activity produced only a modest boost (5%) in a brain area's CMRO 2 (5). The PET results suggest that the energy demand required by neural activity is largely met by anaerobic glycolysis. The metabolism of glucose to lactate does not require oxygen. The more significant issue with regard to functional physiology is the extent to which regional brain activation requires an increase in CMRO 2 . This question remains controversial, because some experiments suggest that neural activation significantly increases CMRO 2 (4,6), while others suggest that neural activation is essentially decoupled with CMRO 2 changes (7).One of the potential factors contributing to the controversy over whether fMRI methods can determine CMRO 2 is the important assumption that the relationship between CBV and CBF fits the power law (8):where ␣ ϭ 2.63 and the subscript "0" is used to refer to the baseline steady-state value of a variable in this study. This quantitative relationship between CBF and CBV was obtained from an early PET study on whole monkey brain under the steady-state condition. It is questionable whether such a quantitative relationship obtained from a whole brain is necessarily applicable to a specific brain region. Rapoport et al. (9) showed that the ␣ values differ among different regions in the rat brain. Furthermore, since the temporal r...
In recent years, the popularity of depth sensors and 3D scanners has led to a rapid development of 3D point clouds. Semantic segmentation of point cloud, as a key step in understanding 3D scenes, has attracted extensive attention of researchers. Recent advances in this topic are dominantly led by deep learning-based methods. In this paper, we provide a survey covering various aspects ranging from indirect segmentation to direct segmentation. Firstly, we review methods of indirect segmentation based on multi-views and voxel grids, as well as direct segmentation methods from different perspectives including point ordering, multi-scale, feature fusion and fusion of graph convolutional neural network (GCNN). Then, the common datasets for point cloud segmentation are exposed to help researchers choose which one is the most suitable for their tasks. Following that, we devote a part of the paper to analyze the quantitative results of these methods. Finally, the development trend of point cloud semantic segmentation technology is prospected.
The present study demonstrates the application of fMRI technology to neuropharmacology and the interaction of drug/receptor in the rat brain. Specifically, we have observed two different types of fMRI signal changes induced by acute i.v. heroin administration in rat brains under conditions of spontaneous and artificial respiration. Under spontaneous respiration, a global decrease in fMRI signal was observed; under artificial respiration, a region-specific increase in fMRI signal was identified and the activation sites are consistent with the distribution of opiate mu-receptors in rat brain as previously reported by autoradiography. Both heroin-induced fMRI signal changes were suppressed by pretreatment of naloxone, an opiate mu-receptor antagonist, and reversed by injection of naloxone following heroin infusion. These results suggest that fMRI has specific advantages in spatial and temporal resolution for studies of neuropharmacology and drugs of abuse.
BackgroundLow back pain is a highly prevalent health problem around the world, affecting 50% to 85% of people at some point in life. The purpose of this systematic review is to summarize the previous proton magnetic resonance spectroscopy studies on brain chemical changes in patients with chronic low back pain (CLBP).MethodsWe identified relevant studies from a literature search of PubMed and EMBASE from 1980 to March 2016. Data extraction was performed on the subjects' characteristics, MRS methods, spectral analyses, cerebral metabolites and perceptual measurements.ResultsThe review identified 9 studies that met the inclusion criteria, comprised of data on 135 CLBP subjects and 137 healthy controls. Seven of these studies reported statistically different neurochemical alterations in patients with CLBP. The results showed that compared to controls, CLBP patients showed reductions of 1) N-acetyl-aspartate (NAA) in the dorsolateral prefrontal cortex (DLPFC), right primary motor cortex, left somatosensory cortex (SSC), left anterior insula and anterior cingulate cortex (ACC); 2) glutamate in the ACC; 3) myo-inositol in the ACC and thalamus; 4) choline in the right SSC; and 5) glucose in the DLPFC.ConclusionThis review provides evidence for alterations in the biochemical profile of the brain in patients with CLBP, which suggests that biochemical changes may play a significant role in the development and pathophysiology of CLBP and shed light on the development of new treatments for CLBP.
A MultiEcho Segmented EPI with z-shimmed BAckground gradient Compensation (MESBAC) pulse sequence is proposed and validated for functional MRI (fMRI) study in regions suffering from severe susceptibility artifacts. This sequence provides an effective tradeoff between spatial and temporal resolution and reduces image distortion and signal dropout. The blood oxygenation level-dependent (BOLD)-weighted fMRI signal can be reliably obtained in the region of the orbitofrontal cortex (OFC). To overcome physiological motion artifacts during prolonged multisegment EPI acquisition, two sets of navigator echoes were acquired in both the readout and phase-encoding directions. Ghost artifacts generally produced by single-shot EPI acquisition were eliminated by separately placing the even and odd echoes in different k-space trajectories. Unlike most z-shim methods that focus on increasing temporal resolution for event-related functional brain mapping, the MESBAC sequence simultaneously addresses problems of image distortion and signal dropout while maintaining sufficient temporal resolution. The MESBAC sequence will be particularly useful for pharmacological and affective fMRI studies in brain regions such as the OFC, nucleus accumbens, amygdala, parahippocampus, etc.Magn T* 2 -weighted gradient echo images are often used in fMRI studies to observe blood oxygenation level-dependent (BOLD) contrast (1) and map brain functions. Long TE values are usually employed during image acquisition to achieve the best contrast between rest and activation states (2). A large-scale susceptibility gradient (Gs) generated at the air-tissue boundaries in the inferior part of the human brain, such as the orbitofrontal cortex (OFC) and the inferior temporal lobe, causes severe image artifacts in the T* 2 -weighted images, making it difficult to measure the BOLD signal in these areas (3). Because the functionality of these brain regions is of great interest in the study of human drug abuse (4) and cognitive function (5), imaging methods that can reduce susceptibility artifacts will make fMRI studies feasible and reliable in these areas.Image distortion and signal dropout are two significant Gs-induced artifacts that occur when a single-shot fast imaging method such as gradient-echo echo-planar imaging (EPI) is employed to achieve high temporal resolution in fMRI studies. Previous studies (6 -8) suggested that image distortion can be corrected if an accurate field map is available. Other strategies to reduce image distortion include the use of a multireference scan (9,10) or acquisition of two images in opposite phase-encoding directions (11). However, while these methods are useful to correct field inhomogeneity, the problem of Gs-induced signal dropout was not solved. High spatial resolution imaging methods (thinner slice) (12,13) have been shown to reduce signal dropout, but in areas with large-scale Gs, such as the OFC, increased spatial resolution (to compensate for the signal dropout) causes a severe loss of spatial coverage. Others have als...
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