122 research outputs found

    Endless microbes most beautiful and most wonderful

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    Since Antonie van Leeuwenhoek first observed microbes, we have come to learn that life on our planet includes not only the macroscopic lifeforms visible to the unaided eye that Charles Darwin studied but also an immense diversity of microbes (Fig 1). We have learned that microorganisms influence nearly every aspect of human existence with beneficial or detrimental effects. With their pivotal roles in biomass conversion, biogeochemical cycles, photosynthesis, and in promoting plant growth, life on this planet ultimately depends on the activities of microorganisms. On the other hand, microorganisms are the etiological agents of many diseases in humans, animals, and plants, causing massive economic losses yearly. Microorganisms also contribute significantly to the production of greenhouse gases such as CO2 and CH4 and, thus, contribute to global warming. In the past decade, we have also learned that microorganisms inhabiting the human body, i.e., the human microbiome, have profound effects on human physiology. Not to forget, some of our most delicious food products and beverages get their distinct qualities from microorganisms, and the pharmaceutical and biotechnological industry relies heavily on microbes. In terms of research, many technological breakthroughs in molecular biology, such as DNA cloning, PCR, and CRISPR-Cas technologies have their origin in microbes. Therefore, research in microbiology is as important now as it ever was

    A noncanonical cytochrome c stimulates calcium binding by PilY1 for type IVa pili formation

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    Type IVa pili (T4aP) are versatile bacterial cell surface structures that undergo extension/adhesion/retraction cycles powered by the cell envelope–spanning T4aP machine. In this machine, a complex composed of four minor pilins and PilY1 primes T4aP extension and is also present at the pilus tip mediating adhesion. Similar to many several other bacteria, Myxococcus xanthus contains multiple minor pilins/PilY1 sets that are incompletely understood. Here, we report that minor pilins and PilY1 (PilY1.1) of cluster_1 form priming and tip complexes contingent on calcium and a noncanonical cytochrome c (TfcP) with an unusual His/Cys heme ligation. We provide evidence that TfcP is unlikely to participate in electron transport and instead stimulates calcium binding by PilY1.1 at low-calcium concentrations, thereby stabilizing PilY1.1 and enabling T4aP function in a broader range of calcium concentrations. These results not only identify a previously undescribed function of cytochromes c but also illustrate how incorporation of an accessory factor expands the environmental range under which the T4aP system functions

    Changed activation, oxygenation, and pain response of chronically painful muscles to repetitive work after training interventions: a randomized controlled trial

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    The aim of this randomized controlled trial was to assess changes in myalgic trapezius activation, muscle oxygenation, and pain intensity during repetitive and stressful work tasks in response to 10 weeks of training. In total, 39 women with a clinical diagnosis of trapezius myalgia were randomly assigned to: (1) general fitness training performed as leg-bicycling (GFT); (2) specific strength training of the neck/shoulder muscles (SST) or (3) reference intervention without physical exercise. Electromyographic activity (EMG), tissue oxygenation (near infrared spectroscopy), and pain intensity were measured in trapezius during pegboard and stress tasks before and after the intervention period. During the pegboard task, GFT improved trapezius oxygenation from a relative decrease of −0.83 ± 1.48 μM to an increase of 0.05 ± 1.32 μM, and decreased pain development by 43%, but did not affect resting levels of pain. SST lowered the relative EMG amplitude by 36%, and decreased pain during resting and working conditions by 52 and 38%, respectively, without affecting trapezius oxygenation. In conclusion, GFT performed as leg-bicycling decreased pain development during repetitive work tasks, possibly due to improved oxygenation of the painful muscles. SST lowered the overall level of pain both during rest and work, possibly due to a lowered relative exposure as evidenced by a lowered relative EMG. The results demonstrate differential adaptive mechanisms of contrasting physical exercise interventions on chronic muscle pain at rest and during repetitive work tasks

    Verification of a distributed summation algorithm

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    A correctness proof of a variant of Segall's Propagation of Information with Feedback protocol is presented. The proof, which is carried out within the I/O automata model of Lynch and Tuttle, is standard except for the use of a prophecy variable. The aim of this paper is to show that, unlike what has been suggested in the literature, assertional methods based on invariant reasoning support an intuitive way to think about and understand this algorithm

    The influence of cardiovascular morbidity on the prognosis in prostate cancer. Experience from a 12-year nationwide Danish population-based cohort study

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    <p>Abstract</p> <p>Background</p> <p>To determine the impact of preexisting ischemic heart disease (IHD) and stroke on overall survival in prostate cancer patients.</p> <p>Methods</p> <p>We conducted a cohort study of patients with incident prostate cancer registered in the Danish Cancer Registry from 1997 through 2008. We identified patients diagnosed with IHD or stroke prior to the date of prostate cancer diagnosis in the Danish National Patient Registry. We constructed Kaplan-Meier curves to analyze time to death and Cox regression was used to estimate hazard ratios (HRs) to compare mortality rates by preexisting IHD or stroke status, adjusting for age, stage, comorbidity, and calendar period.</p> <p>Results</p> <p>Of 30,721 prostate cancer patients, 4,276 (14%) had preexisting IHD and 1,331 (4%) preexisting stroke. Crude 1- and 5-year survival rates were 85% and 44% in men without preexisting IHD or stroke, 81% and 36% in men with preexisting IHD, and 78% and 27% in men with preexisting stroke. Adjusted HRs were 1.05 (95% CI 1.00-1.10) for patients with IHD and 1.20 (95% CI 1.12-1.30) for patients with stroke compared with patients without preexisting IHD or stroke.</p> <p>Conclusions</p> <p>Preexisting IHD had minimal impact on mortality in prostate cancer patients, whereas overall mortality was 20% higher in prostate cancer patients with preexisting stroke compared to those without IHD or stroke. These results highlight the importance of differentiating between various comorbidities.</p

    Comparison of vaccine-induced antibody neutralization against SARS-CoV-2 variants of concern following primary and booster doses of COVID-19 vaccines

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    The SARS-CoV-2 pandemic has, as of July 2022, infected more than 550 million people and caused over 6 million deaths across the world. COVID-19 vaccines were quickly developed to protect against severe disease, hospitalization and death. In the present study, we performed a direct comparative analysis of four COVID-19 vaccines: BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford/AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen), following primary and booster vaccination. We focused on the vaccine-induced antibody-mediated immune response against multiple SARS-CoV-2 variants: wildtype, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and B.1.1.529 (Omicron). The analysis included the quantification of total IgG levels against SARS-CoV-2 Spike, as well as the quantification of antibody neutralization titers. Furthermore, the study assessed the high-throughput ACE2 competition assay as a surrogate for the traditional pseudovirus neutralization assay. The results demonstrated marked differences in antibody-mediated immune responses. The lowest Spike-specific IgG levels and antibody neutralization titers were induced by one dose of the Ad26.COV2.S vaccine, intermediate levels by two doses of the BNT162b2 vaccine, and the highest levels by two doses of the mRNA-1273 vaccine or heterologous vaccination of one dose of the ChAdOx1 vaccine and a subsequent mRNA vaccine. The study also demonstrated that accumulation of SARS-CoV-2 Spike protein mutations was accompanied by a marked decline in antibody neutralization capacity, especially for B.1.1.529. Administration of a booster dose was shown to significantly increase Spike-specific IgG levels and antibody neutralization titers, erasing the differences between the vaccine-induced antibody-mediated immune response between the four vaccines. The findings of this study highlight the importance of booster vaccines and the potential inclusion of future heterologous vaccination strategies for broad protection against current and emerging SARS-CoV-2 variants
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