Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional ...reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyltransferase SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through genome-wide redistribution of heterochromatin, which perturbs chromatin spatial compartmentalization. Together with the enforced activation of the epithelial expression program, cytoskeleton remodeling, reduced proliferation rate and restricted cellular migration, this leads to the reversed oncogenic potential of lung adenocarcinoma cells. These results emphasize an essential role of chromatin architecture in the determination of oncogenic programs and illustrate a relationship between gene expression, epigenome, 3D genome and nuclear mechanics.
The maximal value of the chlorophyll-specific carbon fixation rate in the water column or the optimal assimilation number (Pbopt) is an important parameter used to estimate water column integrated ...primary production (IPP) using models and satellite-derived data. The spatiotemporal variability in the Pbopt of the total and size-fractionated phytoplankton in the Siberian Seas (SSs) and its links with environmental factors were studied based on long-term (1993–2020) field and satellite-derived (MODIS-Aqua) observations. The average value of Pbopt in the SSs was equal to 1.38 ± 0.76 mgC (mg Chl a)–1 h–1. The monthly average values of Pbopt decreased during the growing season from 1.95 mgC (mg Chl a)–1 h–1 in July to 0.64 mgC (mg Chl a)–1 h–1 in October. The average value of Pbopt for small (<3 μm) phytoplankton 1.6-fold exceeded that for large (>3 μm) phytoplankton. The values of Pbopt depend mainly on incident photosynthetically available radiation (PAR). Based on the relationship between Pbopt and PAR, the empirical region-specific algorithm (E0reg) was developed. The E0reg algorithm performed better than commonly used temperature-based models. The application of E0reg for the calculation of Pbopt will make it possible to more precisely estimate IPP in the SSs.
Empirical region-specific (RSM), depth-integrated (DIM) and depth-resolved (DRM) primary production models are developed based on data from the Kara Sea during the autumn (September–October 1993, ...2007, 2011). The model is validated by using field and satellite (MODIS-Aqua) observations. Our findings suggest that RSM algorithms perform better than non-region-specific algorithms (NRSM) in terms of regression analysis, root-mean-square difference (RMSD) and model efficiency. In general, the RSM and NRSM underestimate or overestimate the in situ water column integrated primary production (IPP) by a factor of 2 and 2.8, respectively. Additionally, our results suggest that the model skill of the RSM increases when the chlorophyll specific carbon fixation rate, efficiency of photosynthesis and photosynthetically available radiation (PAR) are used as input variables. The parameterization of chlorophyll (chl a) vertical profiles is performed in Kara Sea waters with different trophic statuses. Model validation with field data suggests that the DIM and DRM algorithms perform equally (RMSD of 0.29 and 0.31, respectively). No changes in the performance of the DIM and DRM algorithms are observed (RMSD of 0.30 and 0.31, respectively) when satellite-derived chl a, PAR and the diffuse attenuation coefficient (Kd) are applied as input variables.
•Region-specific Kara Sea primary production algorithms were developed.•Region-specific algorithms performed better than non-regional-specific algorithms.•Photophysiological variables and incident radiation improved the models.•Parameterization of vertical chlorophyll profiles was performed.•Depth-integrated and depth-resolved algorithms performed equally.
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The chemical and paramagnetic composition of the surface of the tetrafluoroethylene / perfluoro(methyl vinyl ether) copolymer (MFA) was investigated before and after ...γ-irradiation. The content of fluorine and carbon decreases at radiolysis of MFA, as well as the proportion of oxygen increases as a result of the oxidation reaction of radicals formed during γ-irradiation. The electron paramagnetic resonance (EPR) spectrum of the copolymer irradiated at 77 K contains the radicals ∼CF2CFCF2∼ (1) and >CFOCF2 (2). The absence of ∼CF2CF2 radicals, which can be formed at radiolytic rupture of the CC bond of the copolymer main chain is associated with the effect of recombination of the resulting radical pair. The EPR spectrum of irradiated MFA at 300 K only recorded radical (1), which transform into peroxide radicals when air oxygen is introduced into the irradiated sample. Thermomechanical curves of native and radiolyzed MFA show three structural states of the amorphous block (glass, transition region, plateau of highly elastic deformation), as well as melting and molecular flow of the copolymer. The radiothermoluminescence curve shows five maxima associated with the emission of light during the recombination of stabilized ions and radicals during heating of the pre-irradiated MFA at 77 K. The temperature of the luminescence peak maximum at 336 K is close to the temperature of the onset of the devitrification of the chains of the amorphous block of MFA on the thermomechanical curve at 341 K. Irradiation leads to an increase in crystallinity of MFA. The heat of fusion of irradiated MFA on the Differential Scanning Calorimeter (DSC) curve is 50 % higher than the fusion heat of native copolymer. During the heating of γ-irradiated MFA, the relative content of COF molecules in the thermal decomposition products increases by an order of magnitude.
Clinical trials of targeted therapy (TT) and immunotherapy (IT) for highly aggressive advanced melanoma have shown marked improvements in response and survival rates. However, real-world data on ...treatment patterns and clinical outcomes for patients with advanced BRAF V600 mutant melanoma are ultimately scarce. The study was designed as an observational retrospective chart review study, which included 382 patients with advanced BRAF V600 mutant melanoma, who received TT in a real-world setting and were not involved in clinical trials. The data were collected from twelve medical centers in Russia. The objective response rates (ORRs) to combined BRAFi plus MEKi and to BRAFi mono-therapy were 57.4% and 39.8%, respectively. The median progression-free survival (PFS) and median overall survival (OS) were 9.2 months and 22.6 months, respectively, for the combined first-line therapy; 9.4 months and 16.1 months, respectively, for the combined second-line therapy; and 7.4 months and 17.1 months, respectively, for the combined third- or higher-line therapy. Analysis of treatment patterns demonstrated the effectiveness of the combined TT with BRAF plus MEK inhibitors in patients with brain metastases, rare types of BRAF mutations, and across lines of therapy, as well as a well-tolerated and manageable safety profile.
Draft genome sequences of 9 strains of known and putative new species of Microbacteriaceae isolated from insect- and nematode-damaged plants were generated using Illumina technology. The data ...obtained will contribute to the development of the genome-based prokaryote taxonomy and the knowledge on the biology of the microbial group investigated.
Currently, one of the most effective algorithms for state estimation of stochastic systems is a Kalman filter. This filter provides an optimal root-mean-square error in state vector estimation only ...when the parameters of the dynamic system and its observer are precisely known. In real conditions, the observer’s parameters are often inaccurately known; moreover, they change randomly over time. This in turn leads to the divergence of the Kalman estimation process. The problem is currently being solved in a variety of ways. They include the use of interval observers, the use of an extended Kalman filter, the introduction of an additional evaluating observer by nonlinear programming methods, robust scaling of the observer’s transmission coefficient, etc. At the same time, it should be borne in mind that, firstly, all of the above ways are focused on application in specific technical systems and complexes, and secondly, they fundamentally do not allow estimating errors in determining the parameters of the observer themselves in order to compensate them for further improving the accuracy and stability of the filtration process of the state vector. To solve this problem, this paper proposes the use of accurate observations that are irregularly received in a complex measuring system (for example, navigation) for adaptive evaluation of the observer’s true parameters of the stochastic system state vector. The development of the proposed algorithm is based on the analytical dependence of the Kalman estimate variation on the observer’s parameters disturbances obtained using the mathematical apparatus for the study of perturbed multidimensional dynamical systems. The developed algorithm for observer’s parameters adaptive estimation makes it possible to significantly increase the accuracy and stability of the stochastic estimation process as a whole in the time intervals between accurate observations, which is illustrated by the corresponding numerical example.
Introduction: The effectiveness of premedication of patients with arterial hypertension and severe ventricular rhythm disturbances against the background of Amiodarone-associated thyrotoxicosis, high ...anxiety and cyclothymiae disorders should be based on the pharmacological positions of the need to reduce the risk of dangerous adverse cardiovascular reactions.
Materials and methods: During the research, a clinical group of 114 patients with arterial hypertension, severe ventricular arrhythmias and Amiodarone-associated type I thyrotoxicosis was formed: four subgroups were identified. In Subgroup 1 (n=22), no premedication was given. In Subgroup 2 (n=32), premedication was given with Diazepam and magnesium sulfate in a prolonged mode. In Subgroup 3 (n=30), the patients received Diazepam the day before surgery. In Subgroup 4 (n=30), premedication was given with Midazolam. A dynamic assessment of the severity of anxiety, depression, sedation and daily monitoring of blood pressure and ECG were carried out.
Results and discussion: After surgery, in Subgroup 1, the level of anxiety and depression increased. In all other Subgroups, regardless of the type of premedication, the use of benzodiazepines was accompanied by a decrease in the level of anxiety after surgery. A decrease in pressure load and an increase in the stability of the parameters of systemic hemodynamics were registered in Subgroup 2 of patients, whereas in Subgroup 4 of patients, the pressure load increased while limiting the differences in blood pressure values during the day. After surgery, in Subgroup 2, cardiac rhythm disturbances were less common; in Subgroup 3, the structure of rhythmogenesis disturbances in the heart almost did not change, and in Subgroup 4, there was an unfavorable trend of an increase in the frequency of supraventricular, single and group ventricular extrasystoles.
Conclusion: The prolonged premedication with long-acting benzodiazepines and magnesium preparations in patients with arterial hypertension, ventricular rhythm disturbances against the background of Amiodarone-associated thyrotoxicosis reduces the level of anxiety, as well as the risk of developing cardiovascular complications and instability of systemic hemodynamics.
The review summarizes data on the practical aspects of the interaction of nucleic acids with diazapyrene derivatives. The information on biological activity is given and the probable mechanisms ...underlying the action of diazapyrenes are analyzed. It contains 119 references.
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