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Here, we report the study of molecular dynamics of human OGG1 bound to the oxoGA-containing DNA and OGG1 mutants bound to the APC-containing DNA. We showed that the enzyme low activity is associated with a decrease in the populations of Lys249 and Asp268 properly configured for catalysis. The experimentally measured rate constants for the OGG1 mutants show a good agreement with the models. We conclude that the enzymatic activity of OGG1 is determined majorly by the population density of the catalytically competent conformations of the active site residues Lys249 and Asp268.Exosomes (secreted extracellular vesicles formed in the intracellular vesicular transport system) play a crucial role in distant cell-cell communication. Exosomes transfer active forms of various biomolecules; the molecular composition of the exosomal cargo is a result of targeted selection and depends on the type of producer cells. The mechanisms underlying exosome formation and cargo selection are poorly understood. It is believed that there are several pathways for exosome biogenesis, although the questions about their independence and simultaneous coexistence in the cell still remain open. The least studied topic is the recently discovered mechanism of exosome formation associated with lipid rafts, or membrane lipid microdomains. Here, we present modern concepts and basic hypotheses on the mechanisms of exosome biogenesis and secretion and summarize current data on the involvement of lipid rafts and their constituent molecules in these processes. Special attention is paid to the analysis of possible role in the exosome formation of raft-forming proteins of the SPFH family, components of planar rafts, and caveolin, the main component of caveolae.Thymoquinone is one of the main active components of the essential oil from black cumin (Nigella sativa) seeds. Thymoquinone exhibits a wide range of pharmacological activities, including neuroprotective action demonstrated in the models of brain ischemia/reperfusion, Alzheimer's and Parkinson's diseases, and traumatic brain injury. The neuroprotective effect of thymoquinone is mediated via inhibition of lipid peroxidation, downregulation of proinflammatory cytokines, maintenance of mitochondrial membrane potential, and prevention of apoptosis through inhibition of caspases-3, -8, and -9. Thymoquinone-based mitochondria-targeted antioxidants are accumulated in the mitochondria and exhibit neuroprotective properties in nanomolar concentrations. Thymoquinone reduces the negative effects of acute and chronic forms of brain pathologies. The mechanisms of the pharmacological action of thymoquinone and its chemical derivatives require more comprehensive studying. selleck chemicals llc In this paper, we formulated the prospects of application of thymoquinone and thymoquinone-based drugs in the therapy of neurodegenerative diseases.Recently, there has been a rapid progress in the development of techniques for isothermal amplification of nucleic acids as an alternative to polymerase chain reaction (PCR). The advantage of these methods is that the nucleic acids amplification can be carried out at constant temperature, unlike PCR, which requires cyclic temperature changes. Moreover, isothermal amplification can be conducted directly in living cells. This review describes the principles of isothermal amplification techniques and demonstrates their high efficiency in designing new highly sensitive detection methods of nucleic acids and enzymes involved in their modifications. The data on successful application of isothermal amplification methods for the analysis of cells and biomolecules with the use of DNA/RNA aptamers are presented.Recent technical advances in genomic technology have led to the explosive growth of transcriptome-wide studies at the level of single cells. The review describes the first steps of the single cell proteomics that has originated soon after development of transcriptomics methods. The first studies on the shotgun proteomics of single cells that used liquid chromatography/mass spectrometry have been already published. In these works, the cells were separated by the methods used in transcriptomics studies (e.g., cell sorting) and analyzed by modified mass spectrometry with tandem mass tags. The new proteogenomics approach involving integration of single cell transcriptomics and proteomics data will provide better understanding of the mechanisms of cell interactions in normal development and disease.Cytotoxic T lymphocytes and natural killer cells eliminate infected cells from the organism by triggering programmed cell death (apoptosis). The contents of the lytic granules of killer cells, including pore-forming proteins perforins and proteolytic enzymes granzymes, are released with the following penetration of the released proteins into the target cells. Granzyme B initiates mitochondria-dependent apoptosis via (i) proapoptotic Bid protein, (ii) Mcl-1 and Bim proteins, or (iii) p53 protein. As a result, cytochrome c is released from the mitochondria into the cytoplasm, causing formation of apoptosomes that initiate the proteolytic cascade of caspase activation. Granzymes M, H, and F cause cell death accompanied by the cytochrome c release from the mitochondria. Granzyme A induces generation of reactive oxygen species (ROS), which promotes translocation of the endoplasmic reticulum-associated SET complex to the nucleus where it is cleaved by granzyme A, leading to the activation of nucleases that catalyze single-strand DNA breaks. Granzymes A and B penetrate into the mitochondria and cleave subunits of the respiratory chain complex I. One of the complex I subunits is also a target for caspase-3. Granzyme-dependent damage to complex I leads to the ROS generation and cell death.BACKGROUND Hospice care can improve quality of life for persons nearing end of life, yet little is known about utilization of hospice care among persons residing in long-term care facilities (LTCFs). Given the increasing number of deaths that occur in LTCFs, it is important to examine hospice care practices in LTCFs. AIM The aim of the cross-sectional study was to describe residents who received hospice care in LTCFs and explore factors that can predict hospice use in LTCFs across Canada. This study included 185 715 residents aged 19 years or older in LTCFs in Canada in 2015. RESULTS Of all residents, 2.7% (n = 4973) received hospice care and 6.8% (n = 12 684) were profiled as having an end-stage disease. Among those who received hospice care, most were noted as end stage (89.5%) and had severe physical impairment (Activities of Daily Living Hierarchy Scale ≥ 5, 74.3%), mild-to-severe pain (Pain Scale ≥ 1, 76.0%), and moderate-to-severe health instability (Changes in Health, End-Stage Disease, Signs, and Symptoms Scale ≥3, 82.
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