РАЗЛИЧИЯ В РАБОТЕ ФЕРМЕНТОВ DROSHA И DICER В ОБРАЗЦАХ КОЛОРЕКТАЛЬНОГО РАКА И НОРМАЛЬНОЙ ТКАНИ ТОЛСТОЙ КИШКИ
The necessary stage of epithelial-mesenchymal transformation (EMT) is the loss of apical-basal polarization by cells, in the formation of which an important role is played by the interaction of cells with the basement membrane and its laminins. The effect of the transition of colorectal cancer cell lines from the polarized state (2D) to the absence of apical-basal polarization (3D) on gene expression of epithelial and mesenchymal markers was investigated, and the role of laminins 332 and 411 (LM-332 and LM-411, respectively) in this process. The three studied cell lines, HT-29, HCT-116, and RKO, were found to exhibit different sensitivity to changes in cultivation conditions (2D / 3D) and the presence of laminins. One reason for this may be a difference in the initial state of the cells. It was shown that in the initial, 2D state, the lines under investigation were at different stages of EMT. In the HT-29 line, the expression profile characteristic of epithelial cells prevailed, in RKO, for mesenchymal, and in HCT-116, for the intermediate state. The most sensitive to the effects was the cell line HCT-116. No critical rearrangement of the profile of EMT genes was observed either during the transition from 2D to 3D cultivation or when laminins were added. However, for both effects, changes in the expression of the SNAI1 and ZEB1 genes, which encode transcription factors regulating the process of EMT, were recorded; moreover, the expression of SNAI1 increased in response to treatment with laminin in all three cell lines.
One of the key advances in genome assembly that has led to a significant improvement in contig lengths has been improved algorithms for utilization of paired reads (mate-pairs). While in most assemblers, mate-pair information is used in a post-processing step, the recently proposed Paired de Bruijn Graph (PDBG) approach incorporates the mate-pair information directly in the assembly graph structure. However, the PDBG approach faces difficulties when the variation in the insert sizes is high. To address this problem, we first transform mate-pairs into edge-pair histograms that allow one to better estimate the distance between edges in the assembly graph that represent regions linked by multiple mate-pairs. Further, we combine the ideas of mate-pair transformation and PDBGs to construct new data structures for genome assembly: pathsets and pathset graphs.
Many environmental stimuli present a quasi-rhythmic structure at different timescales that the brain needs to decompose and integrate. Cortical oscillations have been proposed as instruments of sensory de-multiplexing, i.e., the parallel processing of different frequency streams in sensory signals. Yet their causal role in such a process has never been demonstrated. Here, we used a neural microcircuit model to address whether coupled theta–gamma oscillations, as observed in human auditory cortex, could underpin the multiscale sensory analysis of speech. We show that, in continuous speech, theta oscillations can flexibly track the syllabic rhythm and temporally organize the phoneme-level response of gamma neurons into a code that enables syllable identification. The tracking of slow speech fluctuations by theta oscillations, and its coupling to gamma-spiking activity both appeared as critical features for accurate speech encoding. These results demonstrate that cortical oscillations can be a key instrument of speech de-multiplexing, parsing, and encoding.
Papers about natural protection territories
Neuronal nicotinic acetylcholine receptors (NNRs) of the α7 subtype have been shown to contribute to the release of dopamine in the nucleus accumbens. The site of action and the underlying mechanism, however, are unclear. Here we applied a circuit modeling approach, supported by electrochemical in vivo recordings, to clarify this issue. Modeling revealed two potential mechanisms for the drop in accumbal dopamine efflux evoked by the selective α7 partial agonist TC-7020. TC-7020 could desensitize α7 NNRs located predominantly on dopamine neurons or glutamatergic afferents to them or, alternatively, activate α7 NNRs located on the glutamatergic afferents to GABAergic interneurons in the ventral tegmental area. Only the model based on desensitization, however, was able to explain the neutralizing effect of coapplied PNU-120596, a positive allosteric modulator. According to our results, the most likely sites of action are the preterminal α7 NNRs controlling glutamate release from cortical afferents to the nucleus accumbens. These findings offer a rationale for the further investigation of α7 NNR agonists as therapy for diseases associated with enhanced mesolimbic dopaminergic tone, such as schizophrenia and addiction