Antibodies to Lactobacilli and Bifidobacteria in Young Children with Different Propensity to Develop Islet Autoimmunity

Peer reviewe

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

AbstractObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a prior genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously-validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson’s r=0.77 and 0.76, respectively, across SNPs with p &lt; 4.4 × 10−4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45×10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per sd = 1.07, p = 0.004), but no other primary stroke subtypes (all p &gt; 0.1).ConclusionsGenetic risk for AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.</jats:sec

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Vaskoksiidi ja h\uf5beda nanoosakeste ning pol\ufcoksometalaat-ioonvedelike toksilisuse uuringud meditsiiniliselt oluliste bakterite ja imetajarakkudega in vitro. Toxicological Profiling of Copper Oxide and Silver Nanoparticles and Polyoxometalate Ionic Liquids with Medically Relevant Bacteria and Mammalian Cells in vitro

Doctoral thesis 24/2019 Doktorit\uf6\uf6 24/201

Solubility-driven toxicity of CuO nanoparticles to Caco2 cells and Escherichia coli: effect of sonication energy and test environment

Due to small size and high surface energy nanoparticles (NPs) tend to agglomerate and precipitate. To avoid/diminish that, sonication of NPs stock suspensions prior toxicity testing is often applied. Currently, there is no standardized particle sonication protocol available leading to inconsistent toxicity data, especially if toxicity is driven by NPs' dissolution that may be enhanced by sonication. In this study we addressed the effect of sonication on hydrodynamic size (D), dissolution and toxicity of copper oxide (CuO) NPs to mammalian cell line Caco-2 in vitro and bacteria Escherichia coli in the respective test environments (cell culture MEM medium, bacterial LB medium and deionised (DI) water). NPs were suspended using no sonication, water bath and probe sonication with different energy intensities. Increased sonication energy (i) decreased the D of CuO NPs in all three test environments; (ii) increased dissolution of NPs in MEM medium and their toxicity to Caco-2; (iii) increased dissolution of NPs in LB medium and their bioavailability to E. coli; and (iv) had no effect on dissolution and antibacterial effects of NPs in DI water. Thus, to reduce variations in dissolution and toxicity, we recommend sonication of NPs in DI water following the dilution into suitable test media

Synergistic antibacterial effect of copper and silver nanoparticles and their mechanism of action

Abstract Bacterial infections are one of the leading causes of death worldwide. In the case of topical bacterial infections such as wound infections, silver (Ag) has historically been one of the most widely used antibacterials. However, scientific publications have demonstrated the adverse effects of silver on human cells, ecotoxicity and insufficient antibacterial effect for the complete elimination of bacterial infections. The use of Ag in the form of nanoparticles (NPs, 1–100 nm) allows to control the release of antibacterial Ag ions but is still not sufficient to eliminate infection and avoid cytotoxicity. In this study, we tested the potency of differently functionalized copper oxide (CuO) NPs to enhance the antibacterial properties of Ag NPs. The antibacterial effect of the mixture of CuO NPs (CuO, CuO–NH2 and CuO–COOH NPs) with Ag NPs (uncoated and coated) was studied. CuO and Ag NP combinations were more efficient than Cu or Ag (NPs) alone against a wide range of bacteria, including antibiotic-resistant strains such as gram-negative Escherichia coli and Pseudomonas aeruginosa as well as gram-positive Staphylococcus aureus, Enterococcus faecalis and Streptococcus dysgalactiae. We showed that positively charged CuO NPs enhanced the antibacterial effect of Ag NPs up to 6 times. Notably, compared to the synergy of CuO and Ag NPs, the synergy of respective metal ions was low, suggesting that NP surface is required for the enhanced antibacterial effect. We also studied the mechanisms of synergy and showed that the production of Cu+ ions, faster dissolution of Ag+ from Ag NPs and lower binding of Ag+ by proteins of the incubation media in the presence of Cu2+ were the main mechanisms of the synergy. In summary, CuO and Ag NP combinations allowed increasing the antibacterial effect up to 6 times. Thus, using CuO and Ag NP combinations enables to retain excellent antibacterial effects due to Ag and synergy and enhances beneficial effects, since Cu is a vital microelement for human cells. Thus, we suggest using combinations of Ag and CuO NPs in antibacterial materials, such as wound care products, to increase the antibacterial effect of Ag, improve safety and prevent and cure topical bacterial infections

Antimicrobial activity of polyoxometalate ionic liquids against clinically relevant pathogens

The activity of a new class of antimicrobials—polyoxometalate ionic liquids (POM‐ILs)—is systematically investigated. The prototype POM‐ILs feature Keggin‐type anions (α‐SiW11O398−) and tetraalkylammonium ions as active cationic species. Antimicrobial tests of the POM‐ILs against important human pathogens show that variation of the alkyl chain length of the cation leads to significant changes in antimicrobial activity against the medically relevant Gram‐negative bacteria Escherichia coli and Pseudomonas aeruginosa, and especially against the Gram‐positive Staphylococcus aureus. Owing to the unique materials properties of the POM‐ILs, such as high viscosity and water immiscibility, applications of antimicrobial surface coatings against airborne pathogens or for water decontamination can be envisaged. Furthermore, the combination of antimicrobially active cations with POM anions might afford new POM‐ILs with two active components.Financial support by the IUT23‐5 and PUT1015 of the Estonian Ministry of Education and Research (A.‐L.K., A.K., O.B.), Fonds der Chemischen Industrie (S.H., C.S.), Fundación General CSIC (S.G.M., Programa ComFuturo), EU COST Action CM1203 (L.K.) and Ulm University (L.K., S.H., C.S.) is gratefully acknowledged.Peer reviewe

Antibacterial and Antiviral Effects of Ag, Cu and Zn Metals, Respective Nanoparticles and Filter Materials Thereof against Coronavirus SARS-CoV-2 and Influenza A Virus

Due to the high prevalence of infectious diseases and their concurrent outbreaks, there is a high interest in developing novel materials with antimicrobial properties. Antibacterial and antiviral properties of a range of metal-based nanoparticles (NPs) are a promising means to fight airborne diseases caused by viruses and bacteria. The aim of this study was to test antimicrobial metals and metal-based nanoparticles efficacy against three viruses, namely influenza A virus (H1N1; A/WSN/1933) and coronaviruses TGEV and SARS-CoV-2; and two bacteria, Escherichia coli and Staphylococcus aureus. The efficacy of ZnO, CuO, and Ag NPs and their respective metal salts, i.e., ZnSO4, CuSO4, and AgNO3, was evaluated in suspensions, and the compounds with the highest antiviral efficacy were chosen for incorporation into fibers of cellulose acetate (CA), using electrospinning to produce filter materials for face masks. Among the tested compounds, CuSO4 demonstrated the highest efficacy against influenza A virus and SARS-CoV-2 (1 h IC50 1.395 mg/L and 0.45 mg/L, respectively), followed by Zn salt and Ag salt. Therefore, Cu compounds were selected for incorporation into CA fibers to produce antiviral and antibacterial filter materials for face masks. CA fibers comprising CuSO4 decreased SARS-CoV-2 titer by 0.38 logarithms and influenza A virus titer by 1.08 logarithms after 5 min of contact; after 1 h of contact, SARS-COV-2 virus was completely inactivated. Developed CuO- and CuSO4-based filter materials also efficiently inactivated the bacteria Escherichia coli and Staphylococcus aureus. The metal NPs and respective metal salts were potent antibacterial and antiviral compounds that were successfully incorporated into the filter materials of face masks. New antibacterial and antiviral materials developed and characterized in this study are crucial in the context of the ongoing SARS-CoV-2 pandemic and beyond

Cubic Iron Core–Shell Nanoparticles Functionalized to Obtain High-Performance MRI Contrast Agents

Nanoparticles with SiO2 coating were synthesized to have a cubic iron core. These were found to have saturation magnetization very close to the highest possible value of any iron-containing nanoparticles and the bulk iron saturation magnetization. The in vitro toxicology studies show that they are highly biocompatible and possess better MRI contrast agent potential than iron oxide NPs