The pattern abnormalities of dendritic spine, tiny protrusions on neuron dendrites, have been found related to multiple nervous system diseases, such as Parkinson's disease and schizophrenia. The determination of the factors affecting spine patterns is of vital importance to explore the pathogenesis of these diseases, and further, search the treatment method for them. Although the study of dendritic spines is a hot topic in neuroscience in recent years, there is still a lack of systematic study on the formation mechanism of its pattern. This paper provided a reinterpretation of reaction-diffusion model to simulate the formation process of dendritic spine, and further, study the factors affecting spine patterns. First, all four classic shapes of spines, mushroom-type, stubby-type, thin-type, and branched-type were reproduced using the model. We found that the consumption rate of substrates by the cytoskeleton is a key factor to regulate spine shape. Moreover, we found that the density of spines can be regulated by the amount of an exogenous activator and inhibitor, which is in accordance with the anatomical results found in hippocampal CA1 in SD rats with glioma. Further, we analyzed the inner mechanism of the above model parameters regulating the dendritic spine pattern through Turing instability analysis and drew a conclusion that an exogenous inhibitor and activator changes Turing wavelength through which to regulate spine densities. Finally, we discussed the deep regulation mechanisms of several reported regulators of dendritic spine shape and densities based on our simulation results. Our work might evoke attention to the mathematic model-based pathogenesis research for neuron diseases which are related to the dendritic spine pattern abnormalities and spark inspiration in the treatment research for these diseases.
This retrospective cross-sectional study included patients with category Ⅲ exposure to the rabies virus at a single center between January and December 2019. Exposure characteristics and clinical data were compared and statistically analyzed among groups willing and unwilling to receive RIG injection, and determinants of its administration were identified by stepwise multivariate logistic regression analyses. In total, 1,757 patients with category Ⅲ exposure were enrolled: 845 males ( 48.1%) and 912 females (51.9%; median age: 28 [9-50] years). Among them, 1,297 (73.8%) received RIG injection (median age: 28 [8-50] years) and 460 (26.2%) refused to receive the injection (median age: 25 [15-48] years). Patients aged 16-25 years (odds ratio [OR]=3.006, 95% confidence interval [CI]=1.957-4.619), 26-45years (OR=2.940, 95% CI=2.011-4.298), 46-55 years (OR=3.647, 95% CI=2.233-5.959) and over 56 years (OR=6.660, 95% CI=4.009-11.062); those with injuries caused by cats (OR=1.937, 95% CI=1.476-2.542); and people with scratch (OR=3.319, 95% CI= 2.510-4.390), minor (OR=35.281, 95% CI=18.524-64.198), and moderate (OR=12.711, 95% CI=7.221-22.375) injurieswere more likely to refuse injection. The RIG administration level in the settings studied herein is insufficient. Educational and awareness programs should be considered for rabies prevention, especially those targeted at people not injured by dogs, people with minor injuries, and the elderly.
The formation of the gigaseal, a giga Omega-scale seal between the micropipette electrode and cell surface, is the keystone to measuring the extremely weak electric signals of cell ion channels in patch clamp technique. To determine a point on the cell surface facilitating gigaseal formation, 3D cell morphology information is required. However, the current 3D cell morphology measurement methods relying on special devices or easily causing clogging issues of the micropipette electrode due to contact on cells, are usually not applicable in the traditional patch clamp system. Addressing this, a noninvasive 3D cell morphology measurement method was developed in this paper for robotic patch clamp with a higher success rate of gigaseal formation. First, the measured bath impedance of the micropipette electrode was modeled and then utilized to measure the cell surface height noninvasively. Using the measured cell surface heights at key positions, the 3D cell morphology was fitted to determine a contact position on the cell surface to facilitate gigaseal formation. Finally, a robotic whole-patch clamp process was conducted at the determined contact position. Experimental results demonstrated that 100% and 90% success rates of noninvasive 3D cell morphology measurements were achieved on the cultured HEK-293 cells and pyramidal neurons in mouse brain slices, respectively, with an average measurement error of cell surface height less than 0.15 μm. At the determined contact position, significant improvements in success rates of gigaseal formation and whole-cell patch clamp operation were achieved in comparison to the results at the positions recommended in related work. Our research may spike inspiration to improve the success rates of gigaseal formation and patch clamp operation based on 3-D cell morphologies.
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