is a widely used index for quantifying individuals' brain health as deviation from a normative brain aging trajectory. Higher-than-expected
is thought partially to reflect above-average rate of brain ...aging. Here, we explicitly tested this assumption in two independent large test datasets (UK Biobank main and Lifebrain replication; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of
models were estimated in two different training datasets (n ≈ 38,000 main and 1800 individuals replication) based on brain structural features. The results showed no association between cross-sectional
and the rate of brain change measured longitudinally. Rather,
in adulthood was associated with the congenital factors of birth weight and polygenic scores of
assumed to reflect a constant, lifelong influence on brain structure from early life. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.
Achromobacter xylosoxidans is an environmental opportunistic pathogen, which infects an increasing number of immunocompromised patients. In this study we combined genomic analysis of a clinical ...isolated A. xylosoxidans strain with phenotypic investigations of its important pathogenic features. We present a complete assembly of the genome of A. xylosoxidans NH44784-1996, an isolate from a cystic fibrosis patient obtained in 1996. The genome of A. xylosoxidans NH44784-1996 contains approximately 7 million base pairs with 6390 potential protein-coding sequences. We identified several features that render it an opportunistic human pathogen, We found genes involved in anaerobic growth and the pgaABCD operon encoding the biofilm adhesin poly-β-1,6-N-acetyl-D-glucosamin. Furthermore, the genome contains a range of antibiotic resistance genes coding efflux pump systems and antibiotic modifying enzymes. In vitro studies of A. xylosoxidans NH44784-1996 confirmed the genomic evidence for its ability to form biofilms, anaerobic growth via denitrification, and resistance to a broad range of antibiotics. Our investigation enables further studies of the functionality of important identified genes contributing to the pathogenicity of A. xylosoxidans and thereby improves our understanding and ability to treat this emerging pathogen.
Abstract
Bacterial reduction in Hg2+ to Hg0, mediated by the mercuric reductase (MerA), is important in the biogeochemical cycling of Hg in temperate environments. Little is known about the ...occurrence and diversity of merA in the Arctic. Seven merA determinants were identified among bacterial isolates from High Arctic snow, freshwater and sea-ice brine. Three determinants in Bacteriodetes,Firmicutes and Actinobacteria showed < 92% (amino acid) sequence similarity to known merA, while one merA homologue in Alphaproteobacteria and 3 homologues from Betaproteobacteria and Gammaproteobacteria were > 99% similar to known merA's. Phylogenetic analysis showed the BacteroidetesmerA to be part of an early lineage in the mer phylogeny, whereas the Betaproteobacteria and GammaproteobacteriamerA appeared to have evolved recently. Several isolates, in which merA was not detected, were able to reduce Hg2+, suggesting presence of unidentified merA genes. About 25% of the isolates contained plasmids, two of which encoded mer operons. One plasmid was a broad host-range IncP-α plasmid. No known incompatibility group could be assigned to the others. The presence of conjugative plasmids, and an incongruent distribution of merA within the taxonomic groups, suggests horizontal transfer of merA as a likely mechanism for High Arctic microbial communities to adapt to changing mercury concentration.
1 Department of Microbiology, University of Copenhagen, 1307 Copenhagen K, Denmark
2 Unit for Antimicrobial Resistance, The National Food Institute, DTU, Denmark
Correspondence Lars Hestbjerg Hansen ...hestbjerg{at}bi.ku.dk
The conjugative plasmid pOLA52, which confers resistance to olaquindox and other antimicrobial agents through a multidrug efflux pump, was investigated for its ability to promote biofilm formation in Escherichia coli . Screening of a transposon-mutagenized pOLA52 clone library revealed several biofilm-deficient mutants, which all mapped within a putative operon with high homology to the mrkABCDF operon of Klebsiella pneumoniae , where these genes are responsible for type 3 fimbriae expression, attachment to surfaces and biofilm formation. Biofilm formation in microtitre plates and in urinary catheters of clones containing pOLA52 with a disrupted putative mrk operon was reduced by more than 100-fold and 2-fold, respectively, compared to mutants with an intact mrk operon. The conjugative transfer rate of pOLA52 was also significantly lower when the mrk operon was disrupted. Through reverse transcriptase analysis, it was demonstrated that the genes contained in the putative mrk operon were linked and likely to be expressed as a single operon. Immunoblotting with type 3 fimbriae (MrkA)-specific antibodies further verified expression of type 3 fimbriae. When transferred to other, potentially pathogenic, members of the family Enterobacteriaceae , including Klebsiella pneumoniae , Salmonella Typhimurium, Kluyvera sp. and Enterobacter aerogenes , pOLA52 facilitated increased biofilm formation. pOLA52 is believed to represent the first example of a conjugative plasmid encoding type 3 fimbriae, resulting in enhanced conjugation frequencies and biofilm formation of the plasmid-harbouring strain.
Abbreviations: CV, crystal violet; RND, resistance-nodulation-cell division
► A calorimetric approach to cellulase product inhibition has been developed. ► The assay uses unmodified, insoluble cellulose as substrate. ► Glucose- and cellobiose inhibition was quantified for ...five H. jecorina cellulases. ► The strongest inhibition was found for Cel7A/cellobiose and Cel6A/glucose. ► The activity of Cel5A was only weakly affected by the two investigated products.
Product inhibition of cellulolytic enzymes has been deemed a critical factor in the industrial saccharification of cellulosic biomass. Several investigations have addressed this problem using crude enzyme preparations or commercial (mixed) cellulase products, but quantitative information on individual cellulases hydrolyzing insoluble cellulose remains insufficient. Such knowledge is necessary to pinpoint and quantify inhibitory weak-links in cellulose hydrolysis, but has proven challenging to come by. Here we show that product inhibition of mono-component cellulases hydrolyzing unmodified cellulose may be monitored by calorimetry. The key advantage of this approach is that it directly measures the rate of hydrolysis while being essentially blind to the background of added product. We investigated the five major cellulases from Hypocrea jecorina (anamorph: Tricoderma reesei), Cel7A (formerly CBH1), Cel6A (CBH2), Cel7B (EG1), Cel5A (EG2) and Cel12A (EG3), for their sensitivity to the products glucose and cellobiose. The strongest inhibition was found for Cel7A, which showed a 50% activity-loss in 19mM cellobiose (IC50=19mM). The other exoglucanase, Cel6A, was much less inhibited by cellobiose, but showed the highest sensitivity to glucose among all investigated enzymes. The endoglucanases Cel12A and Cel7B were moderately inhibited by cellobiose (IC50=60–80mM), and weakly inhibited by glucose (IC50=350–380mM). The highest resistance to both products was found for Cel5A, which retained about 75% of its activity at the highest investigated concentrations (respectively 65mM cellobiose and 1000mM glucose).
Chlorophyll (Chl) f is the most recently discovered chlorophyll and has only been found in cyanobacteria from wet environments. Although its structure and biophysical properties are resolved, the ...importance of Chl f as an accessory pigment in photosynthesis remains unresolved. We found Chl f in a cyanobacterium enriched from a cavernous environment and report the first example of Chl f-supported oxygenic photosynthesis in cyanobacteria from such habitats. Pigment extraction, hyperspectral microscopy and transmission electron microscopy demonstrated the presence of Chl a and f in unicellular cyanobacteria found in enrichment cultures. Amplicon sequencing indicated that all oxygenic phototrophs were related to KC1, a Chl f-containing cyanobacterium previously isolated from an aquatic environment. Microsensor measurements on aggregates demonstrated oxygenic photosynthesis at 742 nm and less efficient photosynthesis under 768- and 777-nm light probably because of diminished overlap with the absorption spectrum of Chl f and other far-red absorbing pigments. Our findings suggest the importance of Chl f-containing cyanobacteria in terrestrial habitats.
In a randomized trial comparing the proton-pump inhibitor pantoprazole with placebo in the ICU, there was no significant difference in the rate of death at 90 days or in a combined end point of ...clinically meaningful events, which included gastrointestinal bleeding and pneumonia.
Aim
High‐dose quadrivalent influenza vaccine (QIV‐HD) has been shown to be more effective than standard‐dose (QIV‐SD) in reducing influenza infection, but whether diabetes status affects relative ...vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin HbA1c (∆HbA1c), incident diabetes, total all‐cause hospitalizations (first + recurrent), and a composite of all‐cause mortality and hospitalization for pneumonia or influenza.
Methods
DANFLU‐1 was a pragmatic, open‐label trial randomizing adults (65‐79 years) 1:1 to QIV‐HD or QIV‐SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all‐cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c.
Results
Of the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV‐HD, compared with QIV‐SD, was associated with a reduction in the rate of all‐cause hospitalizations irrespective of diabetes overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76‐0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55‐1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76‐1.01), pinteraction = 0.62. Among those with diabetes, QIV‐HD was associated with a lower risk of the composite outcome 2 vs. 11 events, HR: 0.18, 95% CI (0.04‐0.83) but had no effect on ∆HbA1c; QIV‐HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (−0.9 to 1.2). QIV‐HD did not affect the risk of incident diabetes HR 1.18, 95% CI (0.94‐1.47).
Conclusions
In this post‐hoc analysis, QIV‐HD versus QIV‐SD was associated with an increased rVE against the composite of all‐cause death and hospitalization for pneumonia/influenza, and the all‐cause hospitalization rate irrespective of diabetes status.
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