Scientists have established a connection between environmental exposure to toxins like β--methylamino-l-alanine (BMAA) and a heightened risk of neurodegenerative disorders. BMAA is a byproduct from certain strains of cyanobacteria that are present in ecosystems worldwide and is renowned for its bioaccumulation and biomagnification in seafood. The sensitivity, selectivity, and reproducibility of the current analytical techniques are insufficient to support efforts regarding food safety and environment monitoring adequately.
View Article and Find Full Text PDFIn recent years, new evidence has shown that the SOS response plays an important role in the response to antimicrobials, with involvement in the generation of clinical resistance. Here we evaluate the impact of heterogeneous expression of the SOS response in clinical isolates of Escherichia coli on response to the fluoroquinolone, ciprofloxacin. In silico analysis of whole genome sequencing data showed remarkable sequence conservation of the SOS response regulators, RecA and LexA.
View Article and Find Full Text PDFIntroduction/objective: Suppression of the SOS response in combination with drugs damaging DNA has been proposed as a potential target to tackle antimicrobial resistance. The SOS response is the pathway used to repair bacterial DNA damage induced by antimicrobials such as quinolones. The extent of -regulated protein expression and other associated systems under pressure of agents that damage bacterial DNA in clinical isolates remains unclear.
View Article and Find Full Text PDFGenome-wide association studies (GWAS) have mapped over 90% of disease- and quantitative-trait-associated variants within the non-coding genome. Non-coding regulatory DNA (e.g.
View Article and Find Full Text PDFBackground: Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at ≤16 mg/L (susceptible with increased exposure) based on a dose of 2 g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemase-producing Klebsiella pneumoniae isolates.
Objectives: To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2-producing clinical isolates of K.
Background: BaeS/BaeR is a two-component system of Escherichia coli that controls the expression of porins and efflux pumps. Its role in beta-lactam resistance is limited.
Objectives: To study the role of baeS/baeR two-component system in temocillin resistance in E.
Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are heavily influenced by genetic factors. Genome-wide association studies have mapped >90% of CVD-associated variants within the noncoding genome, which can alter the function of regulatory proteins, such as transcription factors (TFs). However, due to the overwhelming number of single-nucleotide polymorphisms (SNPs) (>500,000) in genome-wide association studies, prioritizing variants for in vitro analysis remains challenging.
View Article and Find Full Text PDFBacterial SOS response is an inducible system of DNA repair and mutagenesis. Streptococci lack a canonical SOS response, but an SOS-like response was reported in some species. The (A)-(D)-carrying prophage Ф1207.
View Article and Find Full Text PDFCardiovascular diseases (CVDs) are the leading cause of death worldwide and are heavily influenced by genetic factors. Genome-wide association studies (GWAS) have mapped > 90% of CVD-associated variants within the non-coding genome, which can alter the function of regulatory proteins, like transcription factors (TFs). However, due to the overwhelming number of GWAS single nucleotide polymorphisms (SNPs) (>500,000), prioritizing variants for in vitro analysis remains challenging.
View Article and Find Full Text PDFThe present work studies the effect of Mn doping on the crystalline structure of the Hap synthesized by the hydrothermal method at 200 °C for 24 h, from Ca(OH) and (NH)HPO, incorporating MnCl to 0.1, 0.5, 1.
View Article and Find Full Text PDFHuman nuclear receptors (NRs) are a superfamily of ligand-responsive transcription factors that have central roles in cellular function. Their malfunction is linked to numerous diseases, and the ability to modulate their activity with synthetic ligands has yielded 16% of all FDA-approved drugs. NRs regulate distinct gene networks, however they often function from genomic sites that lack known binding motifs.
View Article and Find Full Text PDFPolymers (Basel)
May 2023
Articular cartilage is a specialized tissue that provides a smooth surface for joint movement and load transmission. Unfortunately, it has limited regenerative capacity. Tissue engineering, combining different cell types, scaffolds, growth factors, and physical stimulation has become an alternative for repairing and regenerating articular cartilage.
View Article and Find Full Text PDFSummary: Transcription factors (TFs) are proteins that directly interpret the genome to regulate gene expression and determine cellular phenotypes. TF identification is a common first step in unraveling gene regulatory networks. We present CREPE, an R Shiny app to catalogue and annotate TFs.
View Article and Find Full Text PDFJ Biomater Appl
May 2023
Today, regenerative osteogenesis represents a clinical need, due to the incidence of bone defects that involve groups of pathologies ranging from congenital anomalies to traumatic injuries, as well as problems presented surgically. This is why the design of a polymeric biomaterial (scaffold) of chitosan, carboxymethylcellulose, zinc oxide, and calcium carbonate with similar characteristics in terms of composition and bone structure offers high potential to help address this health problem. The technique for obtaining the scaffolds of this research was to develop a physical hydrogel to have the biofunctionality of the active groups of the polymer chains used, then make use of the lyophilization process to obtain three-dimensional (3D) porous scaffolds.
View Article and Find Full Text PDFOlivetol (OLV), as a cannabidiol (CBD) analog, was incorporated in γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes as potential analgesic drug delivery systems (DDS) for dental hypersensitivity (DH) treatment. These DDS have been scarcely employed in oral health, being the first time in case of MOFs loaded with cannabinoids. In vitro experiments using bovine teeth were performed to verify if the drug is able to reach the dentin, where it can flow to the pulp tissues and exert its analgesic effect; enamel and dentin regions were analyzed by synchrotron radiation-based FTIR microspectroscopy.
View Article and Find Full Text PDFThe suppression of the SOS response has been shown to enhance the activity of quinolones. Furthermore, Dam-dependent base methylation has an impact on susceptibility to other antimicrobials affecting DNA synthesis. Here, we investigated the interplay between these two processes, alone and in combination, in terms of antimicrobial activity.
View Article and Find Full Text PDFBiochim Biophys Acta Gene Regul Mech
March 2023
Genome-wide association studies (GWAS) have mapped over 90 % of disease- or trait-associated variants within the non-coding genome, like cis-regulatory elements (CREs). Non-coding single nucleotide polymorphisms (SNPs) are genomic variants that can change how DNA-binding regulatory proteins, like transcription factors (TFs), interact with the genome and regulate gene expression. NKX2-5 is a TF essential for proper heart development, and mutations affecting its function have been associated with congenital heart diseases (CHDs).
View Article and Find Full Text PDFRecA inhibition could be an important strategy to combat antimicrobial resistance because of its key role in the SOS response, DNA repair and homologous recombination contributing to bacterial survival. This study evaluated the impact of RecA inactivation on heteroresistance in clinical isolates of Escherichia coli and their corresponding recA-deficient isogenic strains to multiple classes of antimicrobial agents. A high frequency (>30%) of heteroresistance was observed in this collection of clinical isolates.
View Article and Find Full Text PDFAntibiotics (Basel)
November 2022
Fosfomycin is an antimicrobial that inhibits the biosynthesis of peptidoglycan by entering the bacteria through two channels (UhpT and GlpT). Glycerol is clinically used as a treatment for elevated intracranial pressure and induces the expression of in Glycerol might offer synergistic activity by increasing fosfomycin uptake. The present study evaluates the use of glycerol at physiological concentrations in combination with fosfomycin against a collection of isogenic mutants of fosfomycin-related genes in strains.
View Article and Find Full Text PDFDespite insertions and deletions being the most common structural variants (SVs) found across genomes, not much is known about how much these SVs vary within populations and between closely related species, nor their significance in evolution. To address these questions, we characterized the evolution of indel SVs using genome assemblies of three closely related butterfly species. Over the relatively short evolutionary timescales investigated, up to 18.
View Article and Find Full Text PDFMicrobiol Spectr
August 2022
Escherichia coli ST131 clade C is an important driver for fluoroquinolone resistance (FQ-R). We conducted a prospective observational study in residents from two long-term care facilities (LTCFs) in Seville, Spain, in 2018. Fecal swabs and environmental samples were obtained.
View Article and Find Full Text PDFEnferm Infecc Microbiol Clin (Engl Ed)
April 2022