Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although signaling circuits and gene regulatory networks that regulate pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations to control state transitions remains a fundamental open question. Here, we focus on two distinct models of pluripotency, primed pluripotent stem cells and pre-implantation inner cell mass cells of human embryos to discover that cell fate transitions associate with rapid changes in nuclear shape and volume which collectively alter the nuclear mechanophenotype.
View Article and Find Full Text PDFChromatin organization, facilitated by compartmentalization and loop extrusion, is crucial for proper gene expression and cell viability. Transcription has long been considered important for shaping genome architecture due to its pervasive activity across the genome and impact on the local chromatin environment. Although earlier studies suggested a minimal contribution of transcription to shaping global genome structure, recent insights from high-resolution chromatin contact mapping, polymer simulations, and acute perturbations have revealed its critical role in dynamic chromatin organization at the level of active genes and enhancer-promoter interactions.
View Article and Find Full Text PDFEnhancers are central for the regulation of metazoan transcription but have proven difficult to study, primarily due to a myriad of interdependent variables shaping their activity. Consequently, synthetic biology has emerged as the main approach for dissecting mechanisms of enhancer function. We start by reviewing simple but highly parallel reporter assays, which have been successful in quantifying the complexity of the activator/coactivator mechanisms at enhancers.
View Article and Find Full Text PDFHigh-throughput imaging (HTI) generates complex imaging datasets from a large number of experimental perturbations. Commercial HTI software for image analysis workflows does not allow full customization and adoption of new image processing algorithms in the analysis modules. While open-source HTI analysis platforms provide individual modules in the workflow, like nuclei segmentation, spot detection, or cell tracking, they are often limited in integrating novel analysis modules or algorithms.
View Article and Find Full Text PDFis one of the significant healthcare-associated meningitis agents characterized by multidrug resistance and a high mortality risk. Thirty-seven strains were isolated from thirty-seven patients of Moscow neuro-ICU with meningitis in 2013-2020. The death rate was 37.
View Article and Find Full Text PDFBackground: In the last decade, the importance of hetero-pathogenic enteroaggregative Shiga-toxin-producing for public health has increased. Recently, we described the genetic background of the EAHEC O181:H4 strain of ST678 carrying the gene in prophage and five plasmids, including the plasmid-carrying and genes. Here, we present the morphological and enzymatic characteristics of this strain, as well as susceptibility to antimicrobials, biofilm formation, etc.
View Article and Find Full Text PDFBackground: a member of the ESKAPE group of bacterial pathogens, has developed multi-antimicrobial resistance (AMR), including resistance to carbapenems, which has increased alarmingly due to the acquisition of carbapenemase genes located on specific plasmids.
Methods: Four clinical isolates were collected from four patients of a neuro-intensive care unit in Moscow, Russia, during the point prevalence survey. The AMR phenotype was estimated using the Vitec-2 instrument, and whole genome sequencing (WGS) was done using Illumina and Nanopore technologies.
Hybrid diarrheagenic strains combining genetic markers belonging to different pathotypes have emerged worldwide and have been reported as a public health concern. The most well-known hybrid strain of enteroaggregative hemorrhagic is O104:H4 strain, which was an agent of a serious outbreak of acute gastroenteritis and hemolytic uremic syndrome (HUS) in Germany in 2011. A case of intestinal infection with HUS in St.
View Article and Find Full Text PDFGram-negative bacteria are prevalent pathogens associated with hospital-acquired infections (HAI) that are a major challenge for patient safety, especially in intensive care units [...
View Article and Find Full Text PDFPreviously we showed that the CG9890 protein, which has zinc finger domains, interacts with ENY2-containing complexes and is localized mainly on the promoters of active genes. The CG9890 protein is involved in the regulation of the expression of some of the genes on the promoters of which it is located, and among these genes there are genes for the ecdysone cascade. In this work, the role of the CG9890 protein in the regulation of ecdysone-dependent inducible transcription was studied.
View Article and Find Full Text PDFThe spread of multidrug-resistant Gram-negative bacteria, which is associated with the distribution of beta-lactamase genes and class 1 and 2 integrons, is a global problem. In this study, in the Moscow neurosurgery intensive care unit (neuro-ICU), the high prevalence of the above-stated genes was found to be associated with intestinal and tracheal carriage. Seven-point prevalence surveys, which included 60 patients in the neuro-ICU, were conducted weekly in the period from Oct.
View Article and Find Full Text PDFThis work is devoted to the investigation of biocidal properties of quaternary ammonium compounds (QACs) based on pyridine structures with aromatic spacers, and their widely known analogs, against clinically significant microorganisms. This study is focused on investigating their antimicrobial activity (minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs)), antibiofilm properties (minimum biofilm inhibitory concentrations (MBICs) and minimum biofilm eradication concentrations (MBECs)), synergetic effect with different alcohols in antiseptic formulations, and bacterial resistance development. It was shown that all combined analogue preparations had a higher level of antibacterial activity against the tested bacterial strains, with a 16- to 32-fold reduction in MICs and MBCs compared to previously used antiseptic preparations.
View Article and Find Full Text PDFThe increasing antibiotic resistance is a clinical problem worldwide. Numerous Gram-negative bacteria have already become resistant to the most widely used class of antibacterial drugs, β-lactams. One of the main mechanisms is inactivation of β-lactam antibiotics by bacterial β-lactamases.
View Article and Find Full Text PDFThe significant increase in the number of antibiotic-resistant microorganisms observed in recent years is a public health problem worldwide. One of the molecular mechanisms for the formation of antimicrobial resistance in bacteria is the presence of efflux pumps. The review presents an analysis of experimental studies related to the study of efflux pumps in clinical strains of Pseudomonas aeruginosa, one of the representatives of hospital pathogens of the ESKAPE group.
View Article and Find Full Text PDFThe purpose of this study was the identification of genetic lineages and antimicrobial resistance (AMR) and virulence genes in isolates associated with severe infections in the neuro-ICU. Susceptibility to antimicrobials was determined using the Vitek-2 instrument. AMR and virulence genes, sequence types (STs), and capsular types were identified by PCR.
View Article and Find Full Text PDFThe in vitro antibacterial activity of 11 commercial disinfectant preparations and 8 antiseptics against 10 strains of the bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloaceae and Providencia stuartii obtained from international collections and isolated from neuroresuscitation patients in Moscow in 2018 was studied. The sensitivity of planktonic cultures to the preparations was determined by the method of serial dilutions in broth and the spot method on solid nutrient media, the sensitivity of biofilms by the applicator method. A general pattern was revealed: the level of sensitivity to tested disinfectants in clinical strains was lower than in reference strains.
View Article and Find Full Text PDFcauses both nosocomial and community-associated infections. Among the hypervirulent (hvKP) isolates, K1 is the most common capsular serotype. Here, we report the draft genome sequences of 3 K1-type (sequence type 23) strains isolated from healthy microbiology laboratory staff in Russia.
View Article and Find Full Text PDFHistone-modifying systems play fundamental roles in gene regulation and the development of multicellular organisms. Histone modifications that are enriched at gene regulatory elements have been heavily studied, but the function of modifications found more broadly throughout the genome remains poorly understood. This is exemplified by histone H2A monoubiquitylation (H2AK119ub1), which is enriched at Polycomb-repressed gene promoters but also covers the genome at lower levels.
View Article and Find Full Text PDFFor the local health service, Elizabethkingia meningoseptica remains a relatively new and little-known pathogen, whereas in many countries of Europe, Asia and other continents it is considered as a potential causative agent of nosocomial infections, especially in premature infants and immunocompromised patients. An analysis of the literature data, as well as our results indicate that E. meningoseptica should be considered as a potential pathogen, which is characterized by a unique profile of susceptibility to antimicrobial agents (AMP) and disinfectants.
View Article and Find Full Text PDFIt is known, that Saccharomycetes can accumulate mineral substances with targeted enrichment of the growth medium. However, the influence of the genetic affiliation of the culture and the technological factors of yeast strains, the composition of growth media on the efficiency of essential trace elements incorporation into the biomass and on the change of theirs intracellular components content have hardly been investigated. In this regard, of this work was to select promising races of yeast Saccharomyces cerevisiae, develop a biotechnological method for obtaining food ingredients enriched with selenium and chromium on their basis, and study their trace element composition.
View Article and Find Full Text PDFIn this work, we conducted a genome-wide study of the zinc finger protein CG9890 and showed that it is localized mostly on the promoters of active genes. The CG9890 binding sites are low-nucleosome-density regions and are colocalized with the chromatin modifying and remodeling complexes SAGA and dSWI/SNF, as well as with the ORC replication complex. The CG9890 protein was shown to be involved in the regulation of the expression of some genes on the promoters of which it is located, with the ecdysone cascade genes accounting for a significant percentage of these genes.
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