DNA glycosylases provide antiviral defence in prokaryotes.

Bacteria have adapted to phage predation by evolving a vast assortment of defence systems. Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data. Here, to overcome this limitation, we infected Escherichia coli carrying a soil metagenomic DNA library with the lytic coliphage T4 to isolate clones carrying protective genes.

Where Are Czech Adolescents Active? The Patterns of Movement and Transport Behavior in Different Active Living Domains.

To understand the environmental determinants of physical activity (PA), precise spatial localization is crucial. This cross-sectional study focuses on the spatiotemporal distribution of PA among Czech adolescents (n = 171) using Global Positioning System loggers and accelerometers. The results showed that adolescents spent most of their time in sedentary behavior, with 57.

Present and future outlooks on environmental DNA-based methods for antibiotic discovery.

Novel antibiotics are in constant demand to combat a global increase in antibiotic-resistant infections. Bacterial natural products have been a long-standing source of antibiotic compounds, and metagenomic mining of environmental DNA (eDNA) has increasingly provided new antibiotic leads. The metagenomic small-molecule discovery pipeline can be divided into three main steps: surveying eDNA, retrieving a sequence of interest, and accessing the encoded natural product.

A genome-wide association analysis of loss of ambulation in dystrophinopathy patients suggests multiple candidate modifiers of disease severity.

The major determinant of disease severity in Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD) is whether the dystrophin gene (DMD) mutation truncates the mRNA reading frame or allows expression of a partially functional protein. However, even in the complete absence of dystrophin, variability in disease severity is observed, and candidate gene studies have implicated several genes as modifiers. Here we present the largest genome-wide search to date for loci influencing severity in N = 419 DMD patients.

High-throughput retrieval of target sequences from complex clone libraries using CRISPRi.

The capture of metagenomic DNA in large clone libraries provides the opportunity to study microbial diversity that is inaccessible using culture-dependent methods. In this study, we harnessed nuclease-deficient Cas9 to establish a CRISPR counter-selection interruption circuit (CCIC) that can be used to retrieve target clones from complex libraries. Combining modern sequencing methods with CCIC cloning allows for rapid physical access to the genetic diversity present in natural ecosystems.

Multiplexed mobilization and expression of biosynthetic gene clusters.

Bacterial genomes contain large reservoirs of biosynthetic gene clusters (BGCs) that are predicted to encode unexplored natural products. Heterologous expression of previously unstudied BGCs should facilitate the discovery of additional therapeutically relevant bioactive molecules from bacterial culture collections, but the large-scale manipulation of BGCs remains cumbersome. Here, we describe a method to parallelize the identification, mobilization and heterologous expression of BGCs.

Immune Responses to SARS-CoV-2 Infection and Vaccination in Dialysis Patients and Kidney Transplant Recipients.

Dialysis patients and kidney transplant (KTX) recipients suffer from an impaired immune system and show a decreased response to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination. We performed a retrospective analysis of 1505 serological SARS-CoV-2 measurements obtained from 887 dialysis patients and 86 KTX recipients. The results were separated by patient subgroups (dialysis/KTX) as well as SARS-CoV-2 status.

Smart Watch Versus Classic Receivers: Static Validity of Three GPS Devices in Different Types of Built Environments.

In order to study the relationship between human physical activity and the design of the built environment, it is important to measure the location of human movement accurately. In this study, we compared an inexpensive GPS receiver (Holux RCV-3000) and a frequently used Garmin Forerunner 35 smart watch, with a device that has been validated and recommended for physical activity research (Qstarz BT-Q1000XT). These instruments were placed on six geodetic points, which represented a range of different environments (e.

Rifabutin Acts in Synergy and Is Bactericidal with Frontline Mycobacterium abscessus Antibiotics Clarithromycin and Tigecycline, Suggesting a Potent Treatment Combination.

is a rapidly emerging mycobacterial pathogen causing dangerous pulmonary infections. Because these bacteria are intrinsically multidrug resistant, treatment options are limited and have questionable efficacy. The current treatment regimen relies on a combination of antibiotics, including clarithromycin paired with amikacin and either imipenem or cefoxitin.

Antagonism between Front-Line Antibiotics Clarithromycin and Amikacin in the Treatment of Mycobacterium abscessus Infections Is Mediated by the Gene.

Combinations of antibiotics, each individually effective against , are routinely coadministered based on the concept that this minimizes the spread of antibiotic resistance. However, our data contradict this assumption and instead document antagonistic interactions between two antibiotics (clarithromycin and amikacin) used to treat infections. Clinically relevant concentrations of clarithromycin induced increased resistance to both amikacin and itself.

Fungal infection control by garlic extracts (Allium sativum L.) and modulation of peritoneal macrophages activity in murine model of sporotrichosis.

Garlic (Allium sativum L.) is grown all over the world as seasoning and medicinal vegetable since 3,000 BC. Allicin is the main component of garlic, being attributed to it the most of its biological activities, such as bactericidal, antifungal and antiviral actions.

Complex continuous wavelet coherence for EEG microstates detection in insight and calm meditation.

Complex continuous wavelet coherence (WTC) can be used for non-stationary signals, such as electroencephalograms. Areas of the WTC with a coherence higher than the calculated optimal threshold were obtained, and the sum of their areas was used as a criterion to differentiate between groups of experienced insight-focused meditators, calm-focused meditators and a control group. This method demonstrated the highest accuracy for the real WTC parts in the frontal region, while for the imaginary parts, the highest accuracy was shown for the frontal occipital pairs of electrodes.

Measurements of gamma dose and thermal neutron fluence in phantoms exposed to a BNCT epithermal beam with TLD-700.

Gamma dose and thermal neutron fluence in a phantom exposed to an epithermal neutron beam for boron neutron capture therapy (BNCT) can be measured by means of a single thermoluminescence dosemeter (TLD-700). The method exploits the shape of the glow curve (GC) and requires the gamma-calibration GC (to obtain gamma dose) and the thermal-neutron-calibration GC (to obtain neutron fluence). The method is applicable for BNCT dosimetry in case of epithermal neutron beams from a reactor because, in most irradiation configurations, thermal neutrons give a not negligible contribution to the TLD-700 GC.

Methods for dose measurements in small phantoms irradiated at BNCT epithermal column.

Suitable dosimeter methods have been proposed and tested, to measure the different dose contributions in small phantoms exposed to epithermal/thermal neutron beams designed for BNCT. One method is based on Fricke-gel dosimeter in small tubes of 2.8mm of external diameter, that allow determining profiles of gamma dose and of boron dose.

WhiB7, an Fe-S-dependent transcription factor that activates species-specific repertoires of drug resistance determinants in actinobacteria.

WhiB-like (Wbl) proteins are well known for their diverse roles in actinobacterial morphogenesis, cell division, virulence, primary and secondary metabolism, and intrinsic antibiotic resistance. Gene disruption experiments showed that three different Actinobacteria (Mycobacterium smegmatis, Streptomyces lividans, and Rhodococcus jostii) each exhibited a different whiB7-dependent resistance profile. Heterologous expression of whiB7 genes showed these resistance profiles reflected the host's repertoire of endogenous whiB7-dependent genes.

The mycobacterial antibiotic resistance determinant WhiB7 acts as a transcriptional activator by binding the primary sigma factor SigA (RpoV).

Tuberculosis therapeutic options are limited by the high intrinsic antibiotic resistance of Mycobacterium tuberculosis. The putative transcriptional regulator WhiB7 is crucial for the activation of systems that provide resistance to diverse antibiotic classes. Here, we used in vitro run-off, two-hybrid assays, as well as mutagenic, complementation and protein pull-down experiments, to characterize WhiB7 as an auto-regulatory, redox-sensitive transcriptional activator in Mycobacterium smegmatis.

WhiB7, a transcriptional activator that coordinates physiology with intrinsic drug resistance in Mycobacterium tuberculosis.

Current tuberculosis treatment regimens are notoriously limited, lengthy and becoming increasingly ineffective due to the emergence of drug-resistant mutant strains of Mycobacterium tuberculosis. The intrinsic resistance of M. tuberculosis to the majority of available drugs relies both on the impermeability of its cell envelope, and its ability to activate specific genes and physiological states.

rTMS age-dependent response in treatment-resistant depressed subjects: a mini-review.

Background: In old age, depressive syndromes often affect people with chronic medical illnesses, cognitive impairment, and disability, which can worsen the outcomes of other medical disorders and promote disability. Repetitive magnetic transcranial stimulation (rTMS) is a simple and effective treatment in patients with treatment-resistant depression. Therefore the use of rTMS could be of particular potential benefit in treatment-resistant elderly patients, who often cannot tolerate the higher doses of drugs needed or show phenomena of intolerance and interaction.

KELVIN: a software package for rigorous measurement of statistical evidence in human genetics.

This paper describes the software package KELVIN, which supports the PPL (posterior probability of linkage) framework for the measurement of statistical evidence in human (or more generally, diploid) genetic studies. In terms of scope, KELVIN supports two-point (trait-marker or marker-marker) and multipoint linkage analysis, based on either sex-averaged or sex-specific genetic maps, with an option to allow for imprinting; trait-marker linkage disequilibrium (LD), or association analysis, in case-control data, trio data, and/or multiplex family data, with options for joint linkage and trait-marker LD or conditional LD given linkage; dichotomous trait, quantitative trait and quantitative trait threshold models; and certain types of gene-gene interactions and covariate effects. Features and data (pedigree) structures can be freely mixed and matched within analyses.

The mycobacterial transcriptional regulator whiB7 gene links redox homeostasis and intrinsic antibiotic resistance.

Intrinsic drug resistance in Mycobacterium tuberculosis limits therapeutic options for treating tuberculosis. The mycobacterial transcriptional regulator whiB7 contributes to intrinsic resistance by activating its own expression and many drug resistance genes in response to antibiotics. To investigate whiB7 activation, we constructed a GFP reporter to monitor its expression, and we used it to investigate the whiB7 promoter and to screen our custom library of almost 600 bioactive compounds, including the majority of clinical antibiotics.

A system for the targeted amplification of bacterial gene clusters multiplies antibiotic yield in Streptomyces coelicolor.

Gene clusters found in bacterial species classified as Streptomyces encode the majority of known antibiotics as well as many pharmaceutically active compounds. A site-specific recombination system similar to those that mediate plasmid conjugation was engineered to catalyze tandem amplification of one of these gene clusters in a heterologous Streptomyces species. Three genetic elements were known to be required for DNA amplification in S.

Imaging of gamma and neutron dose distributions at LVR-15 epithermal beam by means of FGLDs.

Gamma and fast neutron dose spatial distributions have been measured at the collimator exit of the epithermal neutron beam of LVR-15 reactor (Řež). Measurements were performed by means of optically analyzed Fricke-gel-layer detectors. The separation of the two dose contributions has been achieved by suitable pixel-to-pixel elaboration of the light transmittance images of Fricke-gel-layer detectors prepared with water and heavy water.

Neutron fluence depth profiles in water phantom on epithermal beam of LVR-15 research reactor.

Horizontal channel with epithermal neutron beam at the LVR-15 research reactor is used mainly for boron neutron capture therapy. Neutron fluence depth profiles in a water phantom characterise beam properties. The neutron fluence (approximated by reaction rates) depth profiles were measured with six different types of activation detectors.

Evaluation of all dose components in the LVR-15 reactor epithermal neutron beam using Fricke gel dosimeter layers.

Fricke gel dosimeters in the form of layers are suitable to reconstruct bidimensional distributions of the absorbed dose; in accordance with their chemical composition and applying suitably developed algorithms, they can provide dose images of the different radiation components in a BNCT field. After the description of the applied method, this work presents the results obtained at the epithermal column of the BNCT facility at the NRI in Rez (CZ). The measured dose distributions are shown in comparison with data taken by means of other dosimeters thermoluminescence dosimeters (TLDs) and with calculations carried out with the Monte Carlo code MCNP5.