Search Results (4)

Astrocytes serve many functions in the brain related to maintaining nerve tissue homeostasis and regulating neuronal function, including synaptic transmission. It is assumed that astrocytes are crucial players in determining the physiological or pathological outcome of the brain aging process and the development of neurodegenerative diseases. Therefore, studies on the peculiarities of astrocyte physiology and interastrocytic signaling during aging are of utmost importance. Calcium waves are one of the main mechanisms of signal transmission between astrocytes, and in the present study we investigated the features of calcium dynamics in primary cultures of murine cortical astrocytes in physiological aging and hypoxia modeling in vitro. Specifically, we focused on the assessment of calcium network dynamics and the restructuring of the functional network architecture in primary astrocytic cultures. Calcium imaging was performed on days 21 (“young” astrocyte group) and 150 (“old” astrocyte group) of cultures’ development in vitro. While the number of active cells and frequency of calcium events were decreased, we observed a reduced degree of correlation in calcium dynamics between neighboring cells, which was accompanied by a reduced number of functionally connected cells with fewer and slower signaling events. At the same time, an increase in the mRNA expression of anti-apoptotic factor Bcl-2 and connexin 43 was observed in “old” astrocytic cultures, which can be considered as a compensatory response of cells with a decreased level of intercellular communication. A hypoxic episode aggravates the depression of the connectivity of calcium dynamics of “young” astrocytes rather than that of “old” ones. Full article

Accumulated experimental data strongly suggest that astrocytes play an important role in the pathogenesis of neurodegeneration, including Alzheimer’s disease (AD). The effect of astrocytes on the calcium activity of neuron–astroglia networks in AD modelling was the object of the present study. We have expanded and improved our approach’s capabilities to analyze calcium activity. We have developed a novel algorithm to construct dynamic directed graphs of both astrocytic and neuronal networks. The proposed algorithm allows us not only to identify functional relationships between cells and determine the presence of network activity, but also to characterize the spread of the calcium signal from cell to cell. Our study showed that Alzheimer’s astrocytes can change the functional pattern of the calcium activity of healthy nerve cells. When healthy nerve cells were cocultivated with astrocytes treated with Aβ42, activation of calcium signaling was found. When healthy nerve cells were cocultivated with 5xFAD astrocytes, inhibition of calcium signaling was observed. In this regard, it seems relevant to further study astrocytic–neuronal interactions as an important factor in the regulation of the functional activity of brain cells during neurodegenerative processes. The approach to the analysis of streaming imaging data developed by the authors is a promising tool for studying the collective calcium dynamics of nerve cells. Full article

A new algorithm for divisive hierarchical clustering of chemical compounds based on 2D structural fragments is suggested. The algorithm is deterministic, and given a random ordering of the input, will always give the same clustering and can process a database up to 2 million records on a standard PC. The algorithm was used for classification of 1,183 antibiotics mixed with 999,994 random chemical structures. Similarity threshold, at which best separation of active and non active compounds took place, was estimated as 0.6. 85.7% of the antibiotics were successfully classified at this threshold with 0.4% of inaccurate compounds. A .sdf file was created with the probe molecules for clustering of external databases. Full article

A compact Modular Chemical Descriptor Language (MCDL) chemical structure editor (Java applet) is described. The small size (approximately 200 KB) of the applet allows its use to display and edit chemical structures in various Internet applications. The editor supports the MCDL format, in which structures are presented in compact canonical form and is capable of restoring bond orders as well as of managing atom and bond drawing overlap. A small database of cage and large cyclic fragment is used for optimal representation of difficult-to-draw molecules. The improved algorithm of the structure diagram generation can be used for other chemical notations that lack atomic coordinates (SMILES, InChI). Full article