11,777 research outputs found
Gelsolin : a regulator of postsynaptic actin assembly and AMPA receptor expression
No full textDendritic spines are the postsynaptic contact sites for the majority of excitatory
synapses in the brain. Synaptic activity influences the number, shape and
motility of dendritic spines and these effects are likely mediated by dynamic
actin filaments, which are highly concentrated in spine heads. Drugs that inhibit
actin dynamics block spine motility and interfere with the development of longterm
potentiation (LTP), a long-lasting increase in synaptic strength considered
to be closely related to learning and memory. This suggests that actin may
serve as a link between activity-induced modulation of synaptic transmission
and long-term changes in synaptic morphology. Despite this evidence for the
importance of actin dynamics in synaptic plasticity, very little is known about its
regulation at the synapse. In particular the mechanisms linking synaptic activity
to the actin cytoskeleton in dendritic spines are not well understood.
The experiments described in this thesis were focused on gelsolin as a
promising candidate for mediating synaptic activity to actin cytoskeleton in
dendritic spines. It is shown here that exposure of cultured hippocampal
neurons to glutamate results in the accumulation of gelsolin in dendritic spines.
This effect is the consequence of activation of NMDA receptors and influx of
Ca2+. It is also shown that the F-actin binding domain of gelsolin is necessary
for its enrichment at postsynaptic sites. Further experiments showed that actin
filaments are more vulnerable to disruption by glutamate stimulation in gelsolin
over-expressing neurons. The disruption of actin filaments in these neurons is
also dependent on NMDA receptor activation and Ca2+ influx. LTD-related
electric field stimulation likewise increased the loss of filamentous actin in
gelsolin expressing cells compared with untransfected cells. The disruption of
actin filaments required the severing function of gelsolin, which is associated
with the specific filament-severing domain (domain 1) of the gelsolin molecule. Severing of F-actin by active gelsolin reduces the amount of AMPA receptors
(GluR1) associated with dendritic spines.
These results indicate that gelsolin plays an important role in linking synaptic
activity to the postsynaptic actin cytoskeleton. Our results are also consistent
with evidence that activation of NMDA receptors and influx of calcium ions play
a crucial role in regulating the actin cytoskeleton in dendritic spines and hence
are involved in the regulation of postsynaptic glutamate receptor plasticity at
excitatory synapses via a feedback mechanism. This could occur in both the
developing and mature brain under both normal and pathologic conditions.
Taken together, our data support a model in which activity-dependent targeting
of proteins into dendritic spines is a major mechanism for regulating synaptic
plasticity at excitatory synapses
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Comprehensive characterization and identification of chemical constituents of Pingwei Powder by ultra high performance liquid chromatography tandem quadrupole-time-of-flight tandem mass spectrometry
No full textPingwei Powder, a basic traditional Chinese medicine (TCM) prescription, was used for treating the chronic colitis, liver cirrhosis, and acute gastritis, etc. However, its systematic chemical characteristics has not been reported, which hinders the interpretation of its therapeutic mechanism, and quality control.To develop a powerful ultra high performance liquid chromatography tandem quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS)-based method for the systematic chemical characterisation of Pingwei Powder, providing a basis for further research on pharmacological substance basis, and quality control of Pingwei Powder. UHPLC-Q-TOF-MS was used to detect a wide range of chemical substances in Pingwei Powder, and the obtained spectral data were imported into PeakView 1.2 software for data processing. Subsequently, the chemical substances in Pingwei Powder were identified by comparison with reference standards, literatures, and the built-in database of SCIEX OS 2.2 software. Finally, the chemical profile of Pingwei Powder was acquired, and 329 chemical components in Pingwei Powder were identified for the first time, mainly including flavonoids, terpenoids, organic acids, alkaloids, phenylpropanoids. Of note, 48 were from Atractylodis Rhizoma, 37 were from Magnoliae Officinalis Cortex, 72 were from Citri Reticulatae Pericarpium, 80 were from Glycyrrhizae Radix et Rhizoma, 32 were from Ginger, 60 were from Ziziphus jujuba. A scientifically efficient and credible method for obtaining the comprehensive chemical profile of Pingwei Powder based on UHPLC-Q-TOF-MS was developed for the first time, providing a basis for further research on pharmacological substance basis, and quality control of Pingwei Powder
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Raw data of Zhao et al., 2022, Geoderma
No full textRaw data associated with Zhao et al., 2022, Geoderma. Any use of the data set should be approved by the corresponding author Kai Yue at "[email protected]".</p
Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor
No full textIn this work, we explored the molecular framework of the known CB1R allosteric modulator PSNCBAM-1 with the aim to generate new bioactive analogs and to deepen the structure-activity relationships of this type of compounds. In particular, the introduction of a NH group between the pyridine ring and the phenyl nucleus generated the amino-phenyl-urea derivative SN15b that behaved as a positive allosteric modulator (PAM), increasing the CB1R binding affinity of the orthosteric ligand CP55,940. The functional activity was evaluated using serum response element (SRE) assay, which assesses the CB1R-dependent activation of the MAPK/ERK signaling pathway. SN15b and the biphenyl-urea analog SC4a significantly inhibited the response produced by CP55,940 in the low ÂμM range, thus behaving as negative allosteric modulators (NAMs). The new derivatives presented here provide further insights about the modulation of CB1R binding and functional activity by allosteric ligands
Chao Yuen Ren (1892–1982)
No full textY. R. Chao is easily the most famous linguist to have come out of China. Born before the end of the last dynasty in China, he received a traditional Confucian education, but was also one of the first Chinese people to be sent to the West for training in modern Western science (under the Boxer Indemnity Fund). The remarkable breadth and scope of his studies included physics, mathematics, linguistics, musical and literary composition, and translation, and he was a pioneer in many of these fields
Gated relational stacked denoising autoencoder with localized author embedding for global citation recommendation
No full textCitation recommendation is an effective and efficient way to facilitate authors finding desired references. This paper presents a novel neural network based model, called gated relational probabilistic stacked denoising autoencoder with localized author (GRSLA) embedding, for global citation recommendation task. Our model is comprised of two modules with different neural network architecture. For each citing and cited papers, we use a gated paper embedding module, which is extended from probabilistic stacked denoising autoencoder (PSDAE) by adding gated units, to obtain their paper vectors. The added gated units are able to utilize text information of cited paper to refine the vector representation of citing paper in multiple semantic levels. For an author in papers, we first apply topic model to obtain his/her semantic neighbors, and then use a localized author embedding (LAE) module to excavate author vector representation from semantic and explicit neighbors. Unlike most graph convolutional network (GCN) based methods, the LAE module is able to avoid computing global Laplacian in whole graph by taking limited neighbors. Moreover, the LAE module can also be stacked to absorb more neighbors, which makes our model have high extendibility. Based on the generation process of GRSLA, we also derive a learning algorithm of our model by maximum a posteriori (MAP) estimation. We conduct experiments on the AAN, DBLP and CORD-19 datasets, and the results show that GRSLA model works well than previous global citation recommendation methods
Pingwei San Ameliorates Spleen Deficiency-Induced Diarrhea through Intestinal Barrier Protection and Gut Microbiota Modulation
No full textPingwei San (PWS) has been used for more than a thousand years as a traditional Chinese medicine prescription for treating spleen-deficiency diarrhea (SDD). Nevertheless, the exact mechanism by which it exerts its antidiarrheal effects remains unclear. The objective of this investigation was to explore the antidiarrheal efficacy of PWS and its mechanism of action in SDD induced by Rhubarb. To this end, UHPLC-MS/MS was used to identify the chemical composition of PWS, while the body weight, fecal moisture content, and colon pathological alterations were used to evaluate the effects of PWS on the Rhubarb-induced rat model of SDD. Additionally, quantitative polymerase chain reaction (qPCR) and immunohistochemistry were employed to assess the expression of inflammatory factors, aquaporins (AQPs), and tight junction markers in the colon tissues. Furthermore, 16S rRNA was utilized to determine the impact of PWS on the intestinal flora of SDD rats. The findings revealed that PWS increased body weight, reduced fecal water content, and decreased inflammatory cell infiltration in the colon. It also promoted the expression of AQPs and tight junction markers and prevented the loss of colonic cup cells in SDD rats. In addition, PWS significantly increased the abundance of Prevotellaceae, Eubacterium_ruminantium_group, and Tuzzerella, while decreasing the abundance of Ruminococcus and Frisingicoccus in the feces of SDD rats. The LEfSe analysis revealed that Prevotella, Eubacterium_ruminantium_group, and Pantoea were relatively enriched in the PWS group. Overall, the findings of this study indicate that PWS exerted a therapeutic effect on Rhubarb-induced SDD in rats by both protecting the intestinal barrier and modulating the imbalanced intestinal microbiota
Modeling nitrogen nutrient loss and ammonia emissions from animal farms
No full textAuthor institution (Zhao): Department of Food, Agricultural, and Biological Engineering, The Ohio State Universit
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