Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage ...arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.
Usually, vertical drains are widely used to improve land reclamation and construction of urban planning, transport and road construction, and agriculture. Vertical drainage systems are drainage ...systems that use pumped wells, open dug wells, or tube wells. There are calculation methods based on pumping curves and calculation methods based on the filtration equation of hydraulic calculation of vertical drainage. In the proposed system, jet apparatus is used in vertical drainage systems. Jet pumps are designed in such a way that they transfer the impulse through the high-speed primary to the secondary flow. Jet devices are widely used in agriculture, mining, oil extraction, and various industries. In addition, they can be used as an independent units or together with pump units.
The study presented in the article is focused on use of graphene obtained by novel microwave-enhanced chemical vapor deposition (MECVD) method as a construction material for 3D porous ...structures—aerogels and sponges. MECVD graphene nanoplatelets-based aerogels were obtained by mixing MECVD graphene nanoplatelets and chitosan, dissolved in 3% acetic acid followed by its freeze drying and carbonization at 800° in inert medium. Surface morphology of aerogels was characterized by SEM. MECVD graphene nanoplatelets-based aerogels are characterized by a porous structure; they are superhydrophobic and possess high sorption capacity with regard to organic liquids of different densities. Polyurethane sponges coated with MECVD graphene can serve as an alternative to aerogels. The process of their obtaining is cheaper and less complicated. They were obtained by facile “dip-coating” method, modifying its surface to increase its hydrophobicity. The resulting sponges are superhydrophobic and superoleophilic, and demonstrate high rate of sorption of organic liquids and can be easily regenerated by squeezing. In addition, they can be used as a separating material in conjunction with vacuum system for continuous and selective collection of organic liquids from the surface of water.
Although modern methods of whole genome DNA methylation analysis have a wide range of applications, they are not suitable for clinical diagnostics due to their high cost and complexity and due to the ...large amount of sample DNA required for the analysis. Therefore, it is crucial to be able to identify a relatively small number of methylation sites that provide high precision and sensitivity for the diagnosis of pathological states. We propose an algorithm for constructing limited subsamples from high-dimensional data to form diagnostic panels. We have developed a tool that utilizes different methods of selection to find an optimal, minimum necessary combination of factors using cross-entropy loss metrics (LogLoss) to identify a subset of methylation sites. We show that the algorithm can work effectively with different genome methylation patterns using ensemble-based machine learning methods. Algorithm efficiency, precision and robustness were evaluated using five genome-wide DNA methylation datasets (totaling 626 samples), and each dataset was classified into tumor and non-tumor samples. The algorithm produced an AUC of 0.97 (95% CI: 0.94-0.99, 9 sites) for prostate adenocarcinoma and an AUC of 1.0 (from 2 to 6 sites) for urothelial bladder carcinoma, two types of kidney carcinoma and colorectal carcinoma. For prostate adenocarcinoma we showed that identified differential variability methylation patterns distinguish cluster of samples with higher recurrence rate (hazard ratio for recurrence = 0.48, 95% CI: 0.05-0.92; log-rank test, p-value < 0.03). We also identified several clusters of correlated interchangeable methylation sites that can be used for the elaboration of biological interpretation of the resulting models and for further selection of the sites most suitable for designing diagnostic panels. LogLoss-BERAF is implemented as a standalone python code and open-source code is freely available from https://github.com/bioinformatics-IBCH/logloss-beraf along with the models described in this article.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Parkinson’s disease (PD) is a neurodegenerative pathology resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Neurotrophic factors (NTFs) and their receptors ...are key regulators of the survival, differentiation, and development of neurons. However, the role of these factors in the pathogenesis of PD is still unclear. Here, we analyzed the expression of NTFs and their receptors in human induced pluripotent stem cells (iPSCs) derived from the fibroblasts of patients with PD and healthy donors (HDs). Four PD-derived iPSC lines with different mutations and three cell lines from HDs at different stages of neuronal differentiation were used for RT-qPCR analysis and ELISA. We found that the mRNA levels of most analyzed genes were altered in PD-derived cells compared with those in HD-derived cells at all stages. Importantly, irrespective of PD-associated mutations, the mRNA levels of the
BDNF
and
GDNF
genes were mostly increased or unchanged in predominantly DA terminally differentiated neurons (TDNs) compared with those in HD-derived cells. Strikingly, in contrast to BDNF and GDNF mRNA levels, BDNF and GDNF protein levels were lower in almost all PD-derived TDNs than in HD-derived cells, thus indicating the dysregulation of NTF expression at the post-transcriptional level. We suggest that this dysregulation is one of the important signs of PD development.
Pressure systems are widely used in almost all areas of the public economy related to liquids. For example, at present, in the supply of drinking water to populated areas in the world, in heating ...systems, in agriculture, in cleaning water basins from muddy flows, in the mining industry, in construction, in the raising of muddy flows, in the chemical industry, in the process of moving muddy flows at the same speed, in pipeline systems of viscous muddy flows efficient systems are being used for transportation and many other purposes. Recently, plastic pipes have been widely used in production. Such pipes are cheap, light, and resistant to various decays, and their installation is relatively easy. One of the main problems in the hydraulic calculation of pressure systems is the determination of the coefficient of hydraulic friction. Recently, many scientists working in the field have been improving the hydraulic calculations of such pipelines. Yet, there is still a lot of theoretical and experimental research to be done. The article presents a method for determining the coefficient of hydraulic friction in plastic pipes in laboratory conditions.
Prostate adenocarcinoma (PRAD) is the second leading cause of cancer-related deaths in men. High variability in DNA methylation and a high rate of large genomic rearrangements are often observed in ...PRAD.
To investigate the reasons for such high variance, we integrated DNA methylation, RNA-seq, and copy number alterations datasets from The Cancer Genome Atlas (TCGA), focusing on PRAD, and employed weighted gene co-expression network analysis (WGCNA). Our results show that only single cluster of co-expressed genes is associated with genomic and epigenomic instability. Within this cluster, TP63 and TRIM29 are key transcription regulators and are downregulated in PRAD. We discovered that TP63 regulates the level of enhancer methylation in prostate basal epithelial cells. TRIM29 forms a complex with TP63 and together regulates the expression of genes specific to the prostate basal epithelium. In addition, TRIM29 binds DNA repair proteins and prevents the formation of the TMPRSS2:ERG gene fusion typically observed in PRAD.
Our study demonstrates that TRIM29 and TP63 are important regulators in maintaining the identity of the basal epithelium under physiological conditions. Furthermore, we uncover the role of TRIM29 in PRAD development.
Analysis of the results of emergency carotid endarterectomy (CEE) against the background of internal carotid artery (ICA) thrombosis in the acute period of acute cerebrovascular accident (ACVA) in ...patients with COVID-19. During the COVID-19 pandemic (April 1, 2020-May 1, 2021), 43 patients with ICA thrombosis and a positive polymerase chain reaction (PCR) result for SARS-CoV-2 were included in this prospective study. In all cases, CEE was performed in the acutest period of ACVA. These patients were included in group 1. The comparison group was represented by 89 patients who underwent CEE in the acute period of stroke, in the period before the COVID-19 pandemic (April 1, 2019-March 1, 2020). According to laboratory parameters, patients with COVID-19 had severe coagulopathy (with an increase in D-dimer: 3832 ± 627.2 ng/mL, fibrinogen: 12.6 ± 3.1 g/L, prothrombin: 155.7 ± 10, 2%), inflammatory syndrome (increased ferritin: 646.2 ± 56.1 ng/mL, C-reactive protein: 161.3 ± 17.2 mg/L, interleukin-6: 183.3 ± 51.7 pg/mL, leukocytosis: 27.3 ± 1.7 10E9/L). In the hospital postoperative period, the groups were comparable in terms of the incidence of deaths (group 1: 2.3%, n = 1; group 2: 1.1%, n = 1; P= 0.81; OR=2.09; 95 % CI = 0.12-34.3) myocardial infarction (group 1: 2.3%, n = 1; group 2: 0%; P= 0.7; OR = 6.3; 95% CI = 0.25-158.5), CVA (group 1: 2.3%, n = 1; group 2: 2.2%, n = 2; P= 0.55; OR = 1.03; 95% CI = 0,.09-11.7). ICA thrombosis and hemorrhagic transformations were not recorded. However, due to severe coagulopathy with ongoing anticoagulant/antiplatelet therapy, patients with COVID-19 more often developed bleeding in the operation area (group 1: 11.6%, n = 5; group 2: 1.1%, n = 1; P= 0.02; OR = 11.5; 95% CI = 1.3-102.5). In all cases, the flow of hemorrhagic discharge came from the drainage localized in the subcutaneous fat. This made it possible to remove skin sutures in a dressing room, suturing the source of bleeding and applying secondary sutures under local anesthesia. Emergency CEE in the acute period of stroke is an effective and safe method of cerebral revascularization in case of ICA thrombosis in conditions of COVID-19.
Abstract
The results of studying the fire foams’ modification using organosilicone compounds are presented in this article. The results of comparative fighting flammable liquid fires (diesel fuel) ...using non-modified foam and modified foam are also studied. It is shown that fire fighting using foam, modified with organosilicone compounds is much more effective, because of the increasing isolating capacity of such foam due to high-solidifying formation of foam which prevent the liquid vapors from getting in the area of chemical reactions and also isolate the flammable liquid from the oxygen of the air. Such a result is possible due to the presence of the mixture of solutions of foaming agent and the organosilicone modifying compound in the structure of the foam – tethraethyl silicate (TES). The results of the study confirm the perspective of using the organic compounds of the silica for improvement the fire extinguishing properties of the foam and its further applying for the fighting with flammable liquid fire.
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