Half a Century of Temperate Non-Forest Vegetation Changes: No Net Loss in Species Richness, but Considerable Shifts in Taxonomic and Functional Composition.

In recent decades, global change and local anthropogenic pressures have severely affected natural ecosystems and their biodiversity. Although disentangling the effects of these factors is difficult, they are reflected in changes in the functional composition of plant communities. We present a comprehensive, large-scale analysis of long-term changes in plant communities of various non-forest habitat types in the Czech Republic based on 1154 vegetation-plot time series from 53 resurvey studies comprising 3909 vegetation-plot records.

A comprehensive analysis of albuminuria in canine chronic kidney disease.

Background: Albuminuria, an important marker of decreased kidney function in chronic kidney disease (CKD), is not routinely used for CKD detection or proteinuria appearance. Its relationships with biochemical parameters and blood pressure in dogs are poorly understood.

Objectives: This study aimed to evaluate the relationship of albuminuria with various CKD markers, its correlation with the urinary protein to creatinine ratio (UPC), and hypertension in dogs with early stages of CKD.

Comparative reassessment of AcrB efflux inhibitors reveals differential impact of specific pump mutations on the activity of potent compounds.

Multidrug resistance poses global challenges, particularly with regard to Gram-negative bacterial infections. In view of the lack of new antibiotics, drug enhancers, such as efflux pump inhibitors (EPIs), have increasingly come into focus. A number of chemically diverse agents have been reported to inhibit AcrB, the main multidrug transporter in , and homologs in other Gram-negative bacteria.

Serious About Getting Old?: Variability of Individual Old Age Risk Management in Czechia.

The global trend of transferring responsibility for dignified aging from the state to individuals is conducive to a variability of alternative attitudes and strategies. Despite having important implications for both the state and individuals, the variability of old age risk management has not been fully appreciated by social policy. Social policy cannot adapt to every individual, but it can reflect various categories of citizens and their patterns of old age risk management.

A Screening of Antimalarials Extends the Range of Known AcrB Efflux Substrates and Reveals Two Candidates with Antimicrobial Drug-Enhancing Activity.

Efflux by resistance nodulation cell division transporters, such as AcrAB-TolC in , substantially contributes to the development of Gram-negative multidrug resistance. Therefore, the finding of compounds that counteract efflux is an urgent goal in the fight against infectious diseases. Previously, an efflux inhibitory activity of the antimalarials mefloquine and artesunate was reported.

Dynamic changes in genomic and social structures in third millennium BCE central Europe.

Europe's prehistory oversaw dynamic and complex interactions of diverse societies, hitherto unexplored at detailed regional scales. Studying 271 human genomes dated ~4900 to 1600 BCE from the European heartland, Bohemia, we reveal unprecedented genetic changes and social processes. Major migrations preceded the arrival of "steppe" ancestry, and at ~2800 BCE, three genetically and culturally differentiated groups coexisted.

Exploring the Contribution of the AcrB Homolog MdtF to Drug Resistance and Dye Efflux in a Multidrug Resistant Isolate.

In , the role of RND-type drug transporters other than the major efflux pump AcrB has largely remained undeciphered (particularly in multidrug resistant pathogens), because genetic engineering in such isolates is challenging. The present study aimed to explore the capability of the AcrB homolog MdtF to contribute to the extrusion of noxious compounds and to multidrug resistance in an clinical isolate with demonstrated expression of this efflux pump. An / double-knockout was engineered, and susceptibility changes with drugs from various classes were determined in comparison to the parental strain and its and single-knockout mutants.

Limited Multidrug Resistance Efflux Pump Overexpression among Multidrug-Resistant Escherichia coli Strains of ST131.

Gram-negative bacteria partly rely on efflux pumps to facilitate growth under stressful conditions and to increase resistance to a wide variety of commonly used drugs. In recent years, sequence type 131 (ST131) has emerged as a major cause of extraintestinal infection frequently exhibiting a multidrug resistance (MDR) phenotype. The contribution of efflux to MDR in emerging MDR clones, however, is not well studied.

New Topoisomerase Inhibitors: Evaluating the Potency of Gepotidacin and Zoliflodacin in Fluoroquinolone-Resistant Escherichia coli upon Inactivation and Differentiating Their Efflux Pump Substrate Nature.

Inactivating in multidrug-resistant with differing sequence types and quinolone resistance-determining mutations reveals remarkably potentiated activity of the first-in-class topoisomerase inhibitors gepotidacin and zoliflodacin. Differences between both structurally unrelated compounds in comparison to fluoroquinolones regarding the selectivity of RND (resistance-nodulation-cell division)-type transporters, efflux inhibitors, and AcrB porter domain mutations were demonstrated. The findings should reinforce efforts to develop efflux-bypassing drugs and provide AcrB targets with critical relevance for this purpose.

Detection of High-Level Rifaximin Resistance in Enteric Bacteria by Agar Screen.

This study aimed at determining the prevalence of rifaximin resistance in a large collection of resistant to third-generation cephalosporins. A simple agar screen was developed to detect high-level resistance. A total of 401 isolates nonsusceptible to third-generation cephalosporins (including 342 and 39 spp.

Efflux-Mediated Resistance to New Oxazolidinones and Pleuromutilin Derivatives in Escherichia coli with Class Specificities in the Resistance-Nodulation-Cell Division-Type Drug Transport Pathways.

A major contribution of the resistance-nodulation-cell division (RND)-transporter AcrB to resistance to oxazolidinones and pleuromutilin derivatives in was confirmed. However, we discovered significant differences in efflux inhibitor activities, specificities of the homologous pump YhiV (MdtF), and the impact of AcrB pathway mutations. Particularly, entrance channel double-mutation I38F I671T and distal binding pocket mutation F615A revealed class-specific transport routes of oxazolidinones and pleuromutilin derivatives.

NMR and IR analysis of natural substances isolated from Cordyceps medicinal mushrooms.

There exist about 750 species of Cordyceps at present. A high price of natural Cordyceps and its lack in nature caused that the attention has been focused to its cultivation in laboratory conditions. The demand for this “fungus-parasite” is still quite high nowadays, as shown by the amount of commercial nutritional supplements.

Proof of an Outer Membrane Target of the Efflux Inhibitor Phe-Arg-β-Naphthylamide from Random Mutagenesis.

Phe-Arg-β-naphthylamide (PAβN) has been characterized as an efflux pump inhibitor (EPI) acting on the major multidrug resistance efflux transporters of Gram-negative bacteria, such as AcrB in . In the present study, in vitro random mutagenesis was used to evolve resistance to the sensitizing activity of PAβN with the aim of elucidating its mechanism of action. A strain was obtained that was phenotypically similar to a previously reported mutant from a serial selection approach that had no efflux-associated mutations.

Mycobacteria exploit nitric oxide-induced transformation of macrophages into permissive giant cells.

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Contribution of AcrAB-TolC to multidrug resistance in an Escherichia coli sequence type 131 isolate.

Drug efflux by resistance-nodulation-cell division (RND)-type transporters, such as AcrAB-TolC of Escherichia coli, is an important resistance mechanism in Gram-negative bacteria; however, its contribution to multidrug resistance (MDR) in clinical isolates is poorly defined. We inactivated acrB of a sequence type 131 E. coli human isolate that showed high-level MDR, but had no mutations within the known efflux-associated local or global regulators.

First report of invasive liver abscess syndrome with endophthalmitis caused by a K2 serotype ST2398 hypervirulent in Germany, 2016.

We report a case of severe infection with liver abscess and endophthalmitis caused by a hypervirulent strain in an immunocompetent German male patient without travel history to Asia. Phenotypic and molecular characterization showed high similarity to the reference genome NTUH-K2044 isolated in Asia. The isolate was assigned as ST2398 (clonal complex 66).

Evidence of a Substrate-Discriminating Entrance Channel in the Lower Porter Domain of the Multidrug Resistance Efflux Pump AcrB.

Efflux pumps of the resistance nodulation cell division (RND) transporter family, such as AcrB of Escherichia coli, play an important role in the development of multidrug resistance, but the molecular basis for their substrate promiscuity is not yet completely understood. From a collection of highly clarithromycin-resistant AcrB periplasmic domain mutants derived from in vitro random mutagenesis, we identified variants with an unusually altered drug resistance pattern characterized by increased susceptibility to many drugs of lower molecular weight, including fluoroquinolones, tetracyclines, and oxazolidinones, but unchanged or increased resistance to drugs of higher molecular weight, including macrolides. Sequencing of 14 such "divergent resistance" phenotype mutants and 15 control mutants showed that this unusual phenotype was associated with mutations at residues I38 and I671 predominantly to phenylalanine and threonine, respectively, both conferring a similar susceptibility pattern.

Cattle grazing in semiarid forestlands: Habitat selection during periods of drought.

Climate change models are predicting increased frequency and severity of droughts in arid and semiarid environments, and these areas are responsible for much of the world's livestock production. Because cattle (Bos Taurus) grazing can impact the abundance, distribution, and ecological function of native plant and animal communities, it is important to understand how cattle might respond to increasingly arid conditions. Here, we evaluate changes in habitat selection by cattle across an 8-yr period as a function of rainfall and other environmental covariates.

Development of tuberculosis in immunocompromised patients with a positive tuberculosis-specific IGRA.

There is a lack of data on the predictive value of tuberculosis (TB) specific interferon-gamma release assays (TIGRAs) for both immunocompetent and immunocompromised individuals. We retrospectively followed up 460 such patients after QuantiFERON®-TB Gold In-Tube (QFT-GIT) testing (mean follow-up 28 months) by reviewing patient charts. A total of 1/38 QFT-GIT-positive and no QFT-GIT-negative patients developed active TB.

FUNDUS FINDINGS IN A PATIENT WITH α-METHLYACYL-COA RACEMASE DEFICIENCY.

Purpose: To describe the ocular findings in a patient with α-methylacyl-CoA racemase deficiency.

Methods: Case report.

Results: A 45-year-old white man presented with seizures, hemiparesis, and altered mental status.