A Developmental Switch in Neurotransmitter Flux Enhances Synaptic Efficacy by Affecting AMPA Receptor Activation

AbstractFormation of glutamatergic synapses entails development of “silent” immature contacts into mature functional synapses. To determine how this transformation occurs, we investigated the development of neurotransmission at single synapses in vitro. Maturation of presynaptic function, assayed with endocytotic markers, followed accumulation of synapsin I. During this period, synaptic transmission was primarily mediated by activation of NMDA receptors, suggesting that most synapses were functionally silent. However, local glutamate application to silent synapses indicated that these synapses contained functional AMPA receptors, suggesting a possible presynaptic locus for silent transmission. Interference with presynaptic vesicle fusion by exposure to tetanus toxin reverted functional to silent transmission, implicating SNARE-mediated fusion as a determinant of the ratio of NMDA:AMPA receptor activation. This work reveals that functional maturation of synaptic transmission involves transformation of presynaptic silent secretion into mature synaptic transmitter release

Effects of different inlet velocity on the polishing quality of abrasive flow machining

In order to study the effect of different inlet velocity on the polishing quality of abrasive flow machining, this paper takes the variable diameter pipe as an example. The fluid dynamic pressure and total energy of abrasive particles under coupling field with different inlet velocities were carried out by using computational fluid dynamics software. The results of numerical analysis show that the polishing quality becomes better with the increase of the inlet velocity. At the same inlet velocity, the smaller the pipe diameter is, the higher the polishing quality will be. Therefore, the optimum inlet velocity can be selected by numerical simulation according to the size of the aperture of workpiece in the actual processing, which can provide technical support for the production

Isoparametric surfaces in 3-dimensional de Sitter space and anti-de Sitter space

A spacelike surface $M$ in 3-dimensional de Sitter space $\mathbb{S}^3_1$ or 3-dimensional anti-de Sitter space $\mathbb{H}^3_1$ is called isoparametric, if $M$ has constant principle curvatures. A timelike surface is called isoparametric, if its minimal polynomial of the shape operator is constant. In this paper, we determine the spacelike isoparametric surfaces and the timelike isoparametric surfacesx in $\mathbb{S}^3_1$ and $\mathbb{H}^3_1$

Optimization of sub-grid scale model for abrasive flow machining curved tube based on large eddy simulation

Abrasive flow machining technology is a new type of precision machining technology. Due to its unique rheological properties, it can process any complex structure and size parts to meet the requirements that conventional machining cannot meet. Combined with the turbulent flow characteristics of the abrasive flow, the large eddy simulation numerical method is used to simulate the machining process of the abrasive flow. The influence of different sub-grid scale models on the simulation results is discussed. Taking curved tube as the research object, the static pressure, dynamic pressure and velocity of different sub-grid models are analyzed to find the best sub-grid scale model. Large eddy simulation method is used to simulate the complex flow channel parts, and the best sub-grid scale model suitable for complex flow channels is determined, which reveals the grinding and polishing rule of abrasive flow and provides academic support for future research. Therefore, it has frontier and important research value

Enhancement of Learning and Memory by Elevating Brain Magnesium

Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed magnesium compound (magnesium-L-threonate, MgT) leads to the enhancement of learning abilities, working memory, and short- and long-term memory in rats. The pattern completion ability was also improved in aged rats. MgT-treated rats had higher density of synaptophysin-/synaptobrevin-positive puncta in DG and CA1 subregions of hippocampus that were correlated with memory improvement. Functionally, magnesium increased the number of functional presynaptic release sites, while it reduced their release probability. The resultant synaptic reconfiguration enabled selective enhancement of synaptic transmission for burst inputs. Coupled with concurrent upregulation of NR2B-containing NMDA receptors and its downstream signaling, synaptic plasticity induced by correlated inputs was enhanced. Our findings suggest that an increase in brain magnesium enhances both short-term synaptic facilitation and long-term potentiation and improves learning and memory functions.National Institutes of Health (U.S.) (NS37342)National Basic Research Program of China (2006CB3031)National Basic Research Program of China (2009CB941303)National Natural Science Foundation (China) (30630026)National High Technology Research and Development Program of China (2007AA02Z443)Tsinghua-Yue-Yuen Medical Sciences Fun

Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Heparanase facilitates the invasion and metastasis of cancer cells, and is over-expressed in many kinds of malignancies. Our studies indicated that heparanase was frequently expressed in advanced gastric cancers. The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells.</p> <p>Methods</p> <p>Three heparanase-specific small interfering RNA (siRNAs) were designed, synthesized, and transfected into cultured gastric cancer cell line SGC-7901. Heparanase expression was measured by RT-PCR, real-time quantitative PCR and Western blot. Cell proliferation was detected by MTT colorimetry and colony formation assay. The <it>in vitro </it>invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis capabilities of cancer cells were measured by tube formation of endothelial cells.</p> <p>Results</p> <p>Transfection of siRNA against 1496-1514 bp of encoding regions resulted in reduced expression of heparanase, which started at 24 hrs and lasted for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase suppressed the cellular proliferation of SGC-7901 cells. In addition, the <it>in vitro </it>invasion and metastasis of cancer cells were attenuated after knock-down of heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the <it>in vitro </it>angiogenesis of cancer cells in a dose-dependent manner.</p> <p>Conclusions</p> <p>These results demonstrated that gene silencing of heparanase can efficiently abolish the proliferation, invasion, metastasis and angiogenesis of human gastric cancer cells <it>in vitro</it>, suggesting that heparanase-specific siRNA is of potential values as a novel therapeutic agent for human gastric cancer.</p