Cytochrome P4501A (the CYP1A1 and CYP1A2 enzymes) are regulated through the aryl hydrocarbon receptor (AhR)-dependent signal transduction pathway and are generally known as enzymes which metabolize anthropogenic xenob...Cytochrome P4501A (the CYP1A1 and CYP1A2 enzymes) are regulated through the aryl hydrocarbon receptor (AhR)-dependent signal transduction pathway and are generally known as enzymes which metabolize anthropogenic xenobiotics such as dioxin to carcinogenic and mutagenic compounds. However, recently the facts of CYP1A activation under physiological conditions or under action of non-dioxin-like compounds appear. In the present study we show that genistein, herbimycin A and geldanamycin (the protein-tyrosine kinase inhibitors) affect in vivo to CYP1A1 activity, the CYP1A1 mRNA level and the CYP1A1 protein level. These data provide insight into the role of protein kinases in CYP1A regulation may facilitate the understanding of CYP1A regulation.展开更多
Introduction: Exploring the EEG alpha oscillations generates considerable interest because there is well known its role in cognitive and psycho emotional aspects of human life. However, till now there isn’t well dete...Introduction: Exploring the EEG alpha oscillations generates considerable interest because there is well known its role in cognitive and psycho emotional aspects of human life. However, till now there isn’t well determined definition what is alpha activity phenomena and which indices are characterize it. Method: This article focuses on the attempt to determine EEG alpha-activity phenomena, its physical, molecular and morphological nature, to highlight its indices and their role in optimal functioning. Results: Specifically, this article examines individual alpha activity indices: 1) the individual alpha peak frequency;2) activation magnitude measured by estimation the amount of alpha amplitude suppression in response to eyes open and individual alpha band width;3) three alpha “autorhythmicity” indices: intra-spindle amplitude variability, spindle length and steepness. Conclusions: Throughout, the article provides a number of suggestions which alpha activity indices and in which conditions could be applied in psycho physiological investigations, what is their role in optimal functioning and what are possible directions for future research.展开更多
Functional MRI was used to map the brains of subjects on-line during the process of media training for the acquisition and improvement of self-regulation mechanisms. The temporal and spatial dynamics of the new neural...Functional MRI was used to map the brains of subjects on-line during the process of media training for the acquisition and improvement of self-regulation mechanisms. The temporal and spatial dynamics of the new neural network formation were studied in real and simulated (false) biofeedback game, and their qualitative characteristics were discussed. It has been shown that immersion into a virtual competitive game, controlled by physiological responses, causes a wide involvement of the cortices, characterized by a high volume of activation in the mid-temporal, occipital and frontal areas, the cuneus and the precuneus. In both forms of media training, high values of activation volume were identified in the cerebellar structures.展开更多
In eukaryotes, the RNase-Ⅲ Dicer often produces length/sequence microRNA (miRNA) variants, called "isomiRs", owing to intrinsic structural/sequence determinants of the miRNA precursors (pre-miRNAs). In this stu...In eukaryotes, the RNase-Ⅲ Dicer often produces length/sequence microRNA (miRNA) variants, called "isomiRs", owing to intrinsic structural/sequence determinants of the miRNA precursors (pre-miRNAs). In this study, we combined biophysics, genetics and biochemistry approaches to study Arabidopsis miR168, the key feedback regulator of central plant silencing effector protein ARGONAUTE1 (AGO1). We identified a motif conserved among plant premiR168 orthologs, which enables flexible internal basepairing underlying at least three metastable structural configurations. These configurations promote alternative, accurate Dicer cleavage events generating length and structural isomiR168 variants with distinctive AGO sorting properties and modes of action. Among these isomiR168s, a duplex with a 22-nt guide strand exhibits strikingly preferential affinity for AGO10, the closest AGO1 paralog. The 22-nt miR168-AGO10 complex antagonizes AGO1 accumulation in part via "transitive RNAi", a silencing-amplification process, to maintain appropriate AGO1 cellular homeostasis. Furthermore, we found that the tombusviral P19 silencing-suppressor protein displays markedly weaker affinity for the 22-nt form among its isomiR168 cargoes, thereby promoting AGO10-directed suppression of AGOl-mediated antiviral silencing. Taken together, these findings indicate that structural flexibility, a previously overlooked property of premiRNAs, considerably increases the versatility and regulatory potential of individual MIRNA genes, and that some pathogens might have evolved the capacity or mechanisms to usurp this property.展开更多
文摘Cytochrome P4501A (the CYP1A1 and CYP1A2 enzymes) are regulated through the aryl hydrocarbon receptor (AhR)-dependent signal transduction pathway and are generally known as enzymes which metabolize anthropogenic xenobiotics such as dioxin to carcinogenic and mutagenic compounds. However, recently the facts of CYP1A activation under physiological conditions or under action of non-dioxin-like compounds appear. In the present study we show that genistein, herbimycin A and geldanamycin (the protein-tyrosine kinase inhibitors) affect in vivo to CYP1A1 activity, the CYP1A1 mRNA level and the CYP1A1 protein level. These data provide insight into the role of protein kinases in CYP1A regulation may facilitate the understanding of CYP1A regulation.
文摘Introduction: Exploring the EEG alpha oscillations generates considerable interest because there is well known its role in cognitive and psycho emotional aspects of human life. However, till now there isn’t well determined definition what is alpha activity phenomena and which indices are characterize it. Method: This article focuses on the attempt to determine EEG alpha-activity phenomena, its physical, molecular and morphological nature, to highlight its indices and their role in optimal functioning. Results: Specifically, this article examines individual alpha activity indices: 1) the individual alpha peak frequency;2) activation magnitude measured by estimation the amount of alpha amplitude suppression in response to eyes open and individual alpha band width;3) three alpha “autorhythmicity” indices: intra-spindle amplitude variability, spindle length and steepness. Conclusions: Throughout, the article provides a number of suggestions which alpha activity indices and in which conditions could be applied in psycho physiological investigations, what is their role in optimal functioning and what are possible directions for future research.
文摘Functional MRI was used to map the brains of subjects on-line during the process of media training for the acquisition and improvement of self-regulation mechanisms. The temporal and spatial dynamics of the new neural network formation were studied in real and simulated (false) biofeedback game, and their qualitative characteristics were discussed. It has been shown that immersion into a virtual competitive game, controlled by physiological responses, causes a wide involvement of the cortices, characterized by a high volume of activation in the mid-temporal, occipital and frontal areas, the cuneus and the precuneus. In both forms of media training, high values of activation volume were identified in the cerebellar structures.
基金The NCCR RNA and disease funded by the Swiss National Science Foundation (SNF 51NF40_141735) for access to the Biomolecular NMR spectrometry platform at ETH ZUrich. This work was supported by an IIF Marie Curie fellowship to TI (no. 329029) and a European Research Council (ERC) advanced grant "Frontiers of RNAi-Ⅱ" to OV (no. 323071).
文摘In eukaryotes, the RNase-Ⅲ Dicer often produces length/sequence microRNA (miRNA) variants, called "isomiRs", owing to intrinsic structural/sequence determinants of the miRNA precursors (pre-miRNAs). In this study, we combined biophysics, genetics and biochemistry approaches to study Arabidopsis miR168, the key feedback regulator of central plant silencing effector protein ARGONAUTE1 (AGO1). We identified a motif conserved among plant premiR168 orthologs, which enables flexible internal basepairing underlying at least three metastable structural configurations. These configurations promote alternative, accurate Dicer cleavage events generating length and structural isomiR168 variants with distinctive AGO sorting properties and modes of action. Among these isomiR168s, a duplex with a 22-nt guide strand exhibits strikingly preferential affinity for AGO10, the closest AGO1 paralog. The 22-nt miR168-AGO10 complex antagonizes AGO1 accumulation in part via "transitive RNAi", a silencing-amplification process, to maintain appropriate AGO1 cellular homeostasis. Furthermore, we found that the tombusviral P19 silencing-suppressor protein displays markedly weaker affinity for the 22-nt form among its isomiR168 cargoes, thereby promoting AGO10-directed suppression of AGOl-mediated antiviral silencing. Taken together, these findings indicate that structural flexibility, a previously overlooked property of premiRNAs, considerably increases the versatility and regulatory potential of individual MIRNA genes, and that some pathogens might have evolved the capacity or mechanisms to usurp this property.