Oxidation of Fe(II) by oxygen (O2) at circumneutral pH occurs abiotically or is mediated by microaerophilic Fe(II)-oxidizing bacteria. Abiotic Fe(II) oxidation(s) compete with microbial processes and ...the relative contribution of abiotic reactions depend on the chemical conditions, e.g. PO2, pH and the presence and identity of ferric (oxyhydr)oxide mineral surfaces, catalyzing the heterogeneous reaction. At circumneutral pH, abiotic Fe(II) oxidation proceeds rapidly, which raises the question how and to which extent neutrophilic microaerophilic Fe(II)-oxidizing bacteria can compete with chemical reactions and gain metabolic energy from microbial Fe(II) oxidation. In this study, we have investigated the environmental constraints for microaerophilic Fe(II) oxidation in a film layer characterized by diffusive supply of both atmospheric O2 (from the top) and dissolved Fe(II) (from the bottom) by use of a numerical model. A coupled diffusion–reaction model was tested at different chemical (pH and alkalinity gradients) and physical (film layer thickness) parameters to investigate their effects on the relative contributions of different reactions (abiotic homogeneous, heterogeneous and biological Fe(II) oxidation) to the overall (net) Fe(II) oxidation. A first order rate constant for biological oxidation was derived from experimental data from simplifcation of a Monod rate law to be 0.06 h−1. The simulations demonstrate distinct spatial oxidation rate patterns for all of the considered reactions. Microaerophilic Fe(II) oxidation is predominant at a uniform pH 6 and a film thickness z of 1 mm with minor importance at pH 7. Maximum biological rates were on the order of 7∙10-10 mol L−1 s−1 and are in the range of experimentally observed values. Minimum rates were close to the thermodynamic limit. In the presence of a pH gradient and z ≤ 1 mm, two distinct zones were observed: an upper zone dominated by abiotic Fe(II) oxidation (pH ∼ 7) and a lower zone dominated by microaerophilic Fe(II) oxidation (pH < 6.3), while the position and extent of the zones depend on the alkalinity. Such separation is strongly amplified for thinner films (z = 0.2 mm). The importance of heterogenous oxidation depends both on the pH and the amount of ferric (oxyhydr)oxides formed which increases with decreasing diffusive O2 supply at z > 1 mm. In combination with high resolution imaging of pH values in a biofilm, our simulations underpin the importance of pH gradients in allowing for the formation of microniches. The conditions suitable for microaerophilic Fe(II) oxidation can be predicted based on reaction time scales and three factors were identified to be especially important: i) a pH low enough (<6.3) to outcompete abiotic processes; ii) sufficiently fast diffusive supply of Fe(II) (e.g. by Fe(III)-reducing bacteria or chemical processes) with O2 concentrations below 150 μmol L−1; iii) sufficient energy gain from Fe(II) oxidation reaction considering the thermodynamic factor FT. We end by discussing strategies that Fe(II)-oxidizing microorganisms can employ to enhance their competitiveness against abiotic reactions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Circulating CD11c
B cells are a key phenomenon in certain types of autoimmunity but have also been described in the context of regular immune responses (i.e., infections, vaccination). Using mass ...cytometry to profile 46 different markers on individual immune cells, we systematically initially confirmed the presence of increased CD11c
B cells in the blood of systemic lupus erythematosus (SLE) patients. Notably, significant differences in the expression of CD21, CD27, and CD38 became apparent between CD11c
and CD11c
B cells. We observed direct correlation of the frequency of CD21
CD27
B cells and CD21
CD38
B cells with CD11c
B cells, which were most pronounced in SLE compared to primary Sjögren's syndrome patients (pSS) and healthy donors (HD). Thus, CD11c
B cells resided mainly within memory subsets and were enriched in CD27
IgD
, CD21
CD27
, and CD21
CD38
B cell phenotypes. CD11c
B cells from all donor groups (SLE, pSS, and HD) showed enhanced CD69, Ki-67, CD45RO, CD45RA, and CD19 expression, whereas the membrane expression of CXCR5 and CD21 were diminished. Notably, SLE CD11c
B cells showed enhanced expression of the checkpoint molecules CD86, PD1, PDL1, CD137, VISTA, and CTLA-4 compared to HD. The substantial increase of CD11c
B cells with a CD21
phenotype co-expressing distinct activation and checkpoint markers, points to a quantitative increased alternate (extrafollicular) B cell activation route possibly related to abnormal immune regulation as seen under the striking inflammatory conditions of SLE which shows a characteristic PD-1/PD-L1 upregulation.
Staphylococcus aureus is a major pathogen causing significant morbidity and mortality worldwide. The emergence of MDR S. aureus strains in the community setting has major implications in disease ...management. However, data regarding the occurrence and patterns of MDR community-associated S. aureus sub-clones is limited.
To use whole-genome sequences to describe the diversity and distribution of resistance mechanisms among community-associated S. aureus isolates.
S. aureus isolates from skin and soft tissue infections (SSTIs) and nasal colonization were collected from patients within 10 primary care clinics from 2007 to 2015. The Illumina Miseq platform was used to determine the genome sequences for 144 S. aureus isolates. Phylogenetic and bioinformatics analyses were performed using in silico tools. The resistome was assembled and compared with the phenotypically derived antibiogram.
Approximately one-third of S. aureus isolates in the South Texas primary care setting were MDR. A higher proportion of SSTI isolates were MDR in comparison with nasal colonization isolates. Individuals with MDR S. aureus SSTIs were more likely to be African American and obese. Furthermore, S. aureus populations are able to acquire and lose antimicrobial resistance genes. USA300 strains were differentiated by a stable chromosomal mutation in gyrA conferring quinolone resistance. The resistomes were highly predictive of antimicrobial resistance phenotypes.
These findings highlight the high prevalence and epidemiological factors associated with MDR S. aureus strains in the community setting and demonstrate the utility of next-generation sequencing to potentially quicken antimicrobial resistance detection and surveillance for targeted interventions.
It is generally assumed that the production of plant fibre textiles in ancient Europe, especially woven textiles for clothing, was closely linked to the development of agriculture through the use of ...cultivated textile plants (flax, hemp). Here we present a new investigation of the 2800 year old Lusehøj Bronze Age Textile from Voldtofte, Denmark, which challenges this assumption. We show that the textile is made of imported nettle, most probably from the Kärnten-Steiermark region, an area which at the time had an otherwise established flax production. Our results thus suggest that the production of woven plant fibre textiles in Bronze Age Europe was based not only on cultivated textile plants but also on the targeted exploitation of wild plants. The Lusehøj find points to a hitherto unrecognized role of nettle as an important textile plant and suggests the need for a re-evaluation of textile production resource management in prehistoric Europe.
Differential diagnosis between childhood onset attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) remains a challenge, mainly due to overlapping symptoms and high rates of ...comorbidity. Despite this, genetic correlation reported for these disorders is low and non-significant. Here we aimed to better characterize the genetic architecture of these disorders utilizing recent large genome-wide association studies (GWAS). We analyzed independent GWAS summary statistics for ADHD (19,099 cases and 34,194 controls) and BD (20,352 cases and 31,358 controls) applying the conditional/conjunctional false discovery rate (condFDR/conjFDR) statistical framework that increases the power to detect novel phenotype-specific and shared loci by leveraging the combined power of two GWAS. We observed cross-trait polygenic enrichment for ADHD conditioned on associations with BD, and vice versa. Leveraging this enrichment, we identified 19 novel ADHD risk loci and 40 novel BD risk loci at condFDR <0.05. Further, we identified five loci jointly associated with ADHD and BD (conjFDR < 0.05). Interestingly, these five loci show concordant directions of effect for ADHD and BD. These results highlight a shared underlying genetic risk for ADHD and BD which may help to explain the high comorbidity rates and difficulties in differentiating between ADHD and BD in the clinic. Improving our understanding of the underlying genetic architecture of these disorders may aid in the development of novel stratification tools to help reduce these diagnostic difficulties.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Using a modified Boyden chamber the effect of three antiinflammatory drugs on the chemotaxis of human neutrophils has been tested in vitro. Gold salt produced a reduction of both neutrophil migration ...and the ability of plasma to attract this cell. Betamethasone decreased chemotaxis by an action on the cell itself but not on the plasma. Aspirin had no effect on this function. These data suggest that antiinflammatory drugs act through different mechanisms and that the reduction of neutrophil chemotaxis may contribute to the antiinflammatory action of gold salts.
Objective To investigate the risk of tumours in the central nervous system among Danish mobile phone subscribers.Design Nationwide cohort study.Setting Denmark.Participants All Danes aged ≥30 and ...born in Denmark after 1925, subdivided into subscribers and non-subscribers of mobile phones before 1995.Main outcome measures Risk of tumours of the central nervous system, identified from the complete Danish Cancer Register. Sex specific incidence rate ratios estimated with log linear Poisson regression models adjusted for age, calendar period, education, and disposable income.Results 358 403 subscription holders accrued 3.8 million person years. In the follow-up period 1990-2007, there were 10 729 cases of tumours of the central nervous system. The risk of such tumours was close to unity for both men and women. When restricted to individuals with the longest mobile phone use—that is, ≥13 years of subscription—the incidence rate ratio was 1.03 (95% confidence interval 0.83 to 1.27) in men and 0.91 (0.41 to 2.04) in women. Among those with subscriptions of ≥10 years, ratios were 1.04 (0.85 to 1.26) in men and 1.04 (0.56 to 1.95) in women for glioma and 0.90 (0.57 to 1.42) in men and 0.93 (0.46 to 1.87) in women for meningioma. There was no indication of dose-response relation either by years since first subscription for a mobile phone or by anatomical location of the tumour—that is, in regions of the brain closest to where the handset is usually held to the head.Conclusions In this update of a large nationwide cohort study of mobile phone use, there were no increased risks of tumours of the central nervous system, providing little evidence for a causal association.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Chemotaxis of human leukocytes was studied in vitro with a microfilter having pores of 3 micrometer used as a substrate for the gradient. Under these conditions, nonsegmented neutrophils did not ...reach the compartment filled with the attractant, but a significant proportion of them did so when filters with larger pores were substituted. When leukocytes from infected patients were tested with the usual 3 micrometer pore filters, chemotaxis was reduced (as previously shown), but less markedly and less frequently in simultaneous experiments with larger pores. In experiments performed under agarose layers instead of filters, nonsegmented neutrophils responded normally to chemoattraction, again suggesting that their impaired migration in filter experiments was a matter of pore size. When leukocytes from infected patients were assayed under agarose, no impairment occurred; on the contrary, a slight increase in both chemotaxis and random motility was observed. It was therefore concluded that some published cases of impaired neutrophil chemotaxis in infection might be due to technical bias related to pore size.
Background: Early implant placement with simultaneous contour augmentation is documented with short‐ and medium‐term studies. The long‐term stability of contour augmentation is uncertain.
Methods: In ...this prospective, cross‐sectional study, 41 patients with an implant‐borne single crown were examined twice, in 2006 and 2010. Clinical, radiologic, and esthetic parameters were assessed at both examinations. In addition, a cone beam computed tomographic (CBCT) image was obtained during the second examination to assess the dimensions of the facial bone wall.
Results: All 41 implants demonstrated ankylotic stability without signs of peri‐implant infection at both examinations. The clinical parameters remained stable over time. Satisfactory esthetic outcomes were noted, as assessed by the pink and white esthetic score (PES/WES) indices. Overall, the PES scores were slightly higher than the WES scores. None of the implants developed mucosal recession over time, as confirmed by values of the distance between implant shoulder and mucosal margin and cast measurements. The periapical radiographs yielded stable peri‐implant bone levels, with a mean distance between implant shoulder and first visible bone‐implant contact value of 2.18 mm. The CBCT analysis demonstrated a mean thickness of the facial bone wall ≈2.2 mm. In two implants (4.9%) no facial bone wall was detectable radiographically.
Conclusions: This prospective cross‐sectional study demonstrates stable peri‐implant hard and soft tissues for all 41 implants examined and satisfactory esthetic outcomes overall. The follow‐up of 5 to 9 years confirmed again that the risk for mucosal recession is low with early implant placement. In addition, contour augmentation with guided bone regeneration was able to establish and maintain a facial bone wall in 95% of patients.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified ...as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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