Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARS-CoV-2 viral proteins in metabolic dysregulation in COVID-19 patients.

Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC-MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.

[DNA Damage Response in Nucleoli].

Nucleoli, the largest subnuclear compartments, are formed around arrays of ribosomal gene repeats transcribed by RNA polymerase I. The primary function of nucleoli is ribosome biogenesis. Specific DNA damage response mechanisms exist to maintain the genomic stability of ribosomal repeats. Here, we provide a snapshot of our current understanding of processes involved in nucleolar DNA damage response. We discuss structure and function of ribosomal repeats, techniques developed for studying DNA damage response in nucleoli, as well as molecular mechanisms of DNA damage-induced repression of nucleolar transcription and nucleoli reorganization.

Cell therapy assisted autotransplantation of olfactory tract into the optic nerve: A potential treatment for optic neuropathy.

Optic neuropathy is an invaliding pathology with diverse clinical manifestation and varying causes. Current understanding of etiopathological aspects of optical neuropathy does not provide an effective treatment protocol. In this article we discuss existing treatment methods, and their effectiveness, evaluated depending on disease etiology. The olfactory tract is a source of olfactory ensheating cells, whose unique properties can have treatment potential in correction of nerve degeneration. Transplantation of an olfactory tract graft into the damaged optic nerve is a technically achievable intervention, though anatomical limitations exist in the proposed surgical access. Optic nerve defects can also be potentially treated with axon growth stimulating therapy (Zymosan and CTP-cAMP). Optic neuropathy can be potentially cured by autotransplantation of a portion of the olfactory tract. Neuroanatomical and histomorphological aspects of olfactory tract autotransplantation into the damaged optic nerve are provided. Feasibility, technical and anatomical features, potential setbacks and limitations are discussed. Anatomical limitations exist, but with current neurosurgical technology can be overcome. Regenerative potential of olfactory tract glial cells plays an important role in nerve restoration and can play a crucial role in further understanding of nerve degeneration treatment.

Strategies for data acquisition using ultrasonic phased arrays.

Ultrasonic phased arrays have produced major benefits in a range of fields, from medical imaging to non-destructive evaluation. The maximum information, which can be measured by an array, corresponds to the Full Matrix Capture (FMC) data acquisition technique and contains all possible combinations of transmitter-receiver signals. However, this method is not fast enough for some applications and can result in a very large volume of data. In this paper, the problem of optimal array data acquisition strategy is considered, that is, how to make the minimum number of array measurements without loss of information. The main result is that under the single scattering assumption the FMC dataset has a specific sparse structure, and this property can be used to design an optimal data acquisition method. An analytical relationship between the minimum number of array firings, maximum steering angle and signal-to-noise ratio is derived, and validated experimentally. An important conclusion is that the optimal number of emissions decreases when the angular aperture of the array increases. It is also shown that plane wave imaging data are equivalent to the FMC dataset, but requires up to an order of magnitude fewer array firings.

Ultrasonic defect characterization using parametric-manifold mapping.

The aim of ultrasonic non-destructive evaluation includes the detection and characterization of defects, and an understanding of the nature of defects is essential for the assessment of structural integrity in safety critical systems. In general, the defect characterization challenge involves an estimation of defect parameters from measured data. In this paper, we explore the extent to which defects can be characterized by their ultrasonic scattering behaviour. Given a number of ultrasonic measurements, we show that characterization information can be extracted by projecting the measurement onto a parametric manifold in principal component space. We show that this manifold represents the entirety of the characterization information available from far-field harmonic ultrasound. We seek to understand the nature of this information and hence provide definitive statements on the defect characterization performance that is, in principle, extractable from typical measurement scenarios. In experiments, the characterization problem of surface-breaking cracks and the more general problem of elliptical voids are studied, and a good agreement is achieved between the actual parameter values and the characterization results. The nature of the parametric manifold enables us to explain and quantify why some defects are relatively easy to characterize, whereas others are inherently challenging.

[Comparative analysis of the synchronization methods of normal and transformed human cells].

Reactions of genetically identical cells to various exogenous and endogenous stimuli can vary significantly. One of the main factors of this non-genetic cellular heterogeneity is the cell cycle. The most convenient way to study the subcellular processes depending on the cell cycle stage is the synchronization of the cells. Toxic inhibitors of DNA replication and/or mitotic spindle assembly are typically used to synchronize cells. It is important to accurately select the synchronization method for a particular experiment. In this study, we performed a comparative analysis of the synchronization methods of normal and transformed human cells, paying special attention to the accuracy of synchronization and toxicity of the methods used.

Resonant Zener tunnelling via zero-dimensional states in a narrow gap diode.

Interband tunnelling of carriers through a forbidden energy gap, known as Zener tunnelling, is a phenomenon of fundamental and technological interest. Its experimental observation in the Esaki p-n semiconductor diode has led to the first demonstration and exploitation of quantum tunnelling in a condensed matter system. Here we demonstrate a new type of Zener tunnelling that involves the resonant transmission of electrons through zero-dimensional (0D) states. In our devices, a narrow quantum well of the mid-infrared (MIR) alloy In(AsN) is placed in the intrinsic (i) layer of a p-i-n diode. The incorporation of nitrogen in the quantum well creates 0D states that are localized on nanometer lengthscales. These levels provide intermediate states that act as "stepping stones" for electrons tunnelling across the diode and give rise to a negative differential resistance (NDR) that is weakly dependent on temperature. These electron transport properties have potential for the development of nanometre-scale non-linear components for electronics and MIR photonics.

Heat Stress-Induced DNA Damage.

Although the heat-stress response has been extensively studied for decades, very little is known about its effects on nucleic acids and nucleic acid-associated processes. This is due to the fact that the research has focused on the study of heat shock proteins and factors (HSPs and HSFs), their involvement in the regulation of transcription, protein homeostasis, etc. Recently, there has been some progress in the study of heat stress effects on DNA integrity. In this review, we summarize and discuss well-known and potential mechanisms of formation of various heat stress-induced DNA damage.

Heat Stress-Induced Transcriptional Repression.

Heat stress is one of the most popular models for studying the regulation of gene expression. For decades, researchers' attention was focused on the study of the mechanisms of transcriptional activation of stress-induced genes. Although the phenomenon of heat stress-induced global transcriptional repression is known for a long time, the exact molecular mechanisms of such a repression are poorly explored. In this mini-review, we attempt to summarize the existing experimental data on heat stress-induced transcriptional repression.

Heat stress induces formation of cytoplasmic granules containing HSC70 protein.

Using indirect immunofluorescence, in this study we showed that the constitutive heat shock protein HSC70 forms granule-like structures in the cytoplasm of human cells several days after the exposure to heat stress. It was shown that this effect is not the result of HSC70 overexpression under heat stress and is not due to the formation of hyperthermia-induced translational stress granules in the cytoplasm.

Siberian peatlands a net carbon sink and global methane source since the early Holocene.

Interpolar methane gradient (IPG) data from ice cores suggest the "switching on" of a major Northern Hemisphere methane source in the early Holocene. Extensive data from Russia's West Siberian Lowland show (i) explosive, widespread peatland establishment between 11.5 and 9 thousand years ago, predating comparable development in North America and synchronous with increased atmospheric methane concentrations and IPGs, (ii) larger carbon stocks than previously thought (70.2 Petagrams, up to approximately 26% of all terrestrial carbon accumulated since the Last Glacial Maximum), and (iii) little evidence for catastrophic oxidation, suggesting the region represents a long-term carbon dioxide sink and global methane source since the early Holocene.

[The role of lead as a harmful factor in the manufacture of crystal products]. / K voprosu o roli svintsa kak vrednogo faktora pri proizvodstve izdelii iz khrustalia.

The article deals with research into dust contamination of crystal processing shops, and contains toxicological data related to different lead-containing dusts. It was established that the dust concentrations containing 51 to 66% silicon dioxide was higher in the crystal-cutting shops as compared with other shops. The content of lead in the dust in the composition and crystal processing shops was higher than that in the crystal-cutting shops. Toxicological express-analysis of different dusts performed on cell-cultures revealed that processing-induced crystal dusts were not as toxic as red lead (lead oxide) dusts.