Selection, characterization, and biosensing applications of DNA aptamers targeting cyanotoxin BMAA.

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.

Heterogeneity of SOS response expression in clinical isolates of Escherichia coli influences adaptation to antimicrobial stress.

In 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.

Impact of suppression of the SOS response on protein expression in clinical isolates of under antimicrobial pressure of ciprofloxacin.

Introduction/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.

Decoding Non-coding Variants: Recent Approaches to Studying Their Role in Gene Regulation and Human Diseases.

Genome-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.

Evaluation of temocillin efficacy against KPC-2-producing Klebsiella pneumoniae isolates in a hollow-fibre infection model.

Background: 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.

Implications of two-component systems EnvZ/OmpR and BaeS/BaeR in in vitro temocillin resistance in Escherichia coli.

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.

Prioritizing cardiovascular disease-associated variants altering NKX2-5 and TBX5 binding through an integrative computational approach.

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.

The (A)/(D)-carrying streptococcal prophage Φ1207.3 encodes an SOS-like system, induced by UV-C light, responsible for increased survival and increased mutation rate.

Bacterial 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.

Prioritizing Cardiovascular Disease-Associated Variants Altering NKX2-5 Binding through an Integrative Computational Approach.

Cardiovascular 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.

Hidden modes of DNA binding by human nuclear receptors.

Human 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.

CREPE: a Shiny app for transcription factor cataloguing.

Summary: 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.

Disease-associated non-coding variants alter NKX2-5 DNA-binding affinity.

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).

Effect of Glycerol on Fosfomycin Activity against .

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.

A butterfly pan-genome reveals that a large amount of structural variation underlies the evolution of chromatin accessibility.

Despite 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.

Prevalence, Incidence, and Risk Factors for Intestinal Colonization Due to Fluoroquinolone-Resistant ST131 Escherichia coli: a Longitudinal Study in Highly Dependent, Long-Term Care Facility Residents.

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.

Higher prevalence of CTX-M-27-producing Escherichia coli belonging to ST131 clade C1 among residents of two long-term care facilities in Southern Spain.

Recently, the emergence of an international lineage of the CTX-M-27-producing clade C1 of Escherichia coli ST131 is being observed. The aim is to see if this strain has also been introduced in our area. Twenty-eight (33%) out of 86 individuals from two LTCFs in Seville were found to be colonized with fluoroquinolone-resistant E.

Role of inorganic phosphate concentrations in in vitro activity of fosfomycin.

Objectives: The objective of this study was to evaluate the in vitro activity of fosfomycin under different physiological concentrations of inorganic phosphate (P).

Methods: The wild-type BW25113 strain, four isogenic mutants (ΔglpT, ΔuhpT, ΔglpT-uhpT, and ΔphoB) and six clinical isolates of Escherichia coli with different fosfomycin susceptibilities were used. EUCAST breakpoints were used.

Clinical characteristics and outcome of bacteraemia caused by Enterobacter cloacae and Klebsiella aerogenes: more similarities than differences.

Objectives: The genus Enterobacter is a common cause of nosocomial infections. Historically, the most frequent Enterobacter species were those of Enterobacter cloacae complex and Enterobacter aerogenes. In 2019, E.

Disbalancing Envelope Stress Responses as a Strategy for Sensitization of to Antimicrobial Agents.

Disbalancing envelope stress responses was investigated as a strategy for sensitization of to antimicrobial agents. Seventeen isogenic strains were selected from the KEIO collection with deletions in genes corresponding to the σ, Cpx, Rcs, Bae, and Psp responses. Antimicrobial activity against 20 drugs with different targets was evaluated by disk diffusion and gradient strip tests.

Detection of Low-Level Fosfomycin-Resistant Variants by Decreasing Glucose-6-Phosphate Concentration in Fosfomycin Susceptibility Determination.

Mutations that confer low-level fosfomycin resistance (LLFR) but not clinical resistance in are increasingly reported. LLFR strains can become clinically resistant under urinary tract physiological conditions or may act as gateways for highly resistant subpopulations by the selection of additional LLFR mutations. Nevertheless, most LLFR strains are impossible to detect under routine fosfomycin susceptibility determinations.

A Laser-Activated Membrane Introduction Mass Spectrometry Study of Proton Spillover Promoted Alkane Dehydrogenation.

Operando high-throughput evaluation of heterogeneous catalysts by laser-activated membrane introduction mass spectrometry (LAMIMS) elucidates the Pt loading dependence of methylcyclohexane dehydrogenation on platinized γ-alumina beads. A CO marking laser rapidly and sequentially heats catalyst beads positioned on a heat-dissipating carbon paper support that overlays a silicone membrane, separating the bead library reaction zone from a quadrupole mass analyzer. The toluene / peak varies logarithmically with Pt loading, suggesting that reactivity includes factors that are negatively correlated to Pt loading.

Contribution of hypermutation to fosfomycin heteroresistance in Escherichia coli.

Objectives: To explore the effect of combining defects in DNA repair systems with the presence of fosfomycin-resistant mechanisms to explain the mechanisms underlying fosfomycin heteroresistance phenotypes in Enterobacteriaceae.

Materials And Methods: We used 11 clinical Escherichia coli isolates together with isogenic single-gene deletion mutants in the E. coli DNA repair system or associated with fosfomycin resistance, combined with double-gene deletion mutants.

A prospective, multicenter case control study of risk factors for acquisition and mortality in Enterobacter species bacteremia.

Background: Enterobacter is among the main etiologies of hospital-acquired infections. This study aims to identify the risk factors of acquisition and attributable mortality of Enterobacter bacteremia.

Methods: Observational, case-control study for risk factors and prospective cohort for outcomes of consecutive cases with Enterobacter bacteremia.