Role of Actin DNase-I-Binding Loop in Myosin Subfragment 1-Induced Polymerization of G-actin: Implications for the Mechanism of Polymerization

AbstractProteolytic cleavage of actin between Gly42 and Val43 within its DNase-I-binding loop (D-loop) abolishes the ability of Ca-G-actin to spontaneously polymerize in the presence of KCl. Here we show that such modified actin is assembled into filaments, albeit at a lower rate than unmodified actin, by myosin subfragment 1 (S1) carrying the A1 essential light chain but not by S1(A2). S1 titration of pyrene-G-actin showed a diminished affinity of cleaved actin for S1, but this could be compensated for by using S1 in excess. The most significant effect of the cleavage, revealed by measuring the fluorescence of pyrene-actin and light-scattering intensities as a function of actin concentration at saturating concentrations of S1, is strong inhibition of association of G-actin-S1 complexes into oligomers. Measurements of the fluorescence of dansyl cadaverine attached to Gln41 indicate substantial inhibition of the initial association of G-actin-S1 into longitudinal dimers. The data provide experimental evidence for the critical role of D-loop conformation in both longitudinal and lateral, cross-strand actin-actin contact formation in the nucleation reaction. Electron microscopic analysis of the changes in filament-length distribution during polymerization of actin by S1(A1) and S1(A2) suggests that the mechanism of S1-induced polymerization is not substantially different from the nucleation-elongation scheme of spontaneous actin polymerization

Optimized metabotype definition based on a limited number of standard clinical parameters in the population-based KORA study

The aim of metabotyping is to categorize individuals into metabolically similar groups. Earlier studies that explored metabotyping used numerous parameters, which made it less transferable to apply. Therefore, this study aimed to identify metabotypes based on a set of standard laboratory parameters that are regularly determined in clinical practice. K-means cluster analysis was used to group 3001 adults from the KORA F4 cohort into three clusters. We identified the clustering parameters through variable importance methods, without including any specific disease endpoint. Several unique combinations of selected parameters were used to create different metabotype models. Metabotype models were then described and evaluated, based on various metabolic parameters and on the incidence of cardiometabolic diseases. As a result, two optimal models were identified: a model composed of five parameters, which were fasting glucose, HDLc, non-HDLc, uric acid, and BMI (the metabolic disease model) for clustering; and a model that included four parameters, which were fasting glucose, HDLc, non-HDLc, and triglycerides (the cardiovascular disease model). These identified metabotypes are based on a few common parameters that are measured in everyday clinical practice. These metabotypes are cost-effective, and can be easily applied on a large scale in order to identify specific risk groups that can benefit most from measures to prevent cardiometabolic diseases, such as dietary recommendations and lifestyle interventions

Association of habitual dietary intake with liver iron: a population-based imaging study

Iron-related disorders of the liver can result in serious health conditions, such as liver cirrhosis. Evidence on the role of modifiable lifestyle factors like nutrition in liver iron storage is lacking. Thus, we aimed to assess the association of habitual diet with liver iron content (LIC). We investigated 303 participants from the population-based KORA-MRI study who underwent whole-body magnetic resonance imaging (MRI). Dietary habits were evaluated using repeated 24 h food lists and a food frequency questionnaire. Sex-stratified multiple linear regression models were applied to quantify the association between nutrition variables of interest and LIC, adjusting for liver fat content (LFC), energy intake, and age. Mean age of participants was 56.4 ± 9.0 years and 44.2% were female. Mean LIC was 1.23 ± 0.12 mg/g dry weight, with higher values in men than in women (1.26 ± 0.13 and 1.20 ± 0.10 mg/g, p < 0.001). Alcohol intake was positively associated with LIC (men: β = 1.94; women: β = 4.98, p-values < 0.03). Significant negative associations with LIC were found for fiber (β = −5.61, p < 0.001) and potassium (β = −0.058, p = 0.034) for female participants only. Furthermore, LIC was highly correlated with liver fat content in both sexes. Our findings suggests that there are sex-specific associations of habitual dietary intake and LIC. Alcohol, fiber, and potassium may play a considerable role in liver iron metabolism

Education and professional development of University Mathematics Teachers

International audienceThe theme of this panel may surprise some, as university teachers of mathematics typically hold a PhD in mathematics or some adjacent field, and in many places some “pedagogical training” is also foreseen. However, university teaching presents still more challenges (in many places: more inhomogeneous or different student groups to teach), and opportunities (including new technology, and – we hope – useful resources from research on UME). For all of these reasons, the panel will address the following questions: What is the current, typical preparation of University Mathematics Teachers for their function as teachers? What “in-service” opportunities for teacher development exist? - naturally, answers will depend both on countries and institutions, but sharing experiences could help to provide an updated picture of how the “professional knowledge of UME teachers” is currently built and sustained. Do the current preparation and opportunities for development meet the demands that exist or can be foreseen? Could the preparation and development opportunities be improved, for instance by giving university teachers (more) access to selected parts of current research on UME, and possibly also participate in research and development projects? What initiatives exist, and which could be imagined as beneficial – both to increase the impact and quality of research on UME, and of UME itself

Education and professional development of University Mathematics Teachers

International audienceThe theme of this panel may surprise some, as university teachers of mathematics typically hold a PhD in mathematics or some adjacent field, and in many places some “pedagogical training” is also foreseen. However, university teaching presents still more challenges (in many places: more inhomogeneous or different student groups to teach), and opportunities (including new technology, and – we hope – useful resources from research on UME). For all of these reasons, the panel will address the following questions: What is the current, typical preparation of University Mathematics Teachers for their function as teachers? What “in-service” opportunities for teacher development exist? - naturally, answers will depend both on countries and institutions, but sharing experiences could help to provide an updated picture of how the “professional knowledge of UME teachers” is currently built and sustained. Do the current preparation and opportunities for development meet the demands that exist or can be foreseen? Could the preparation and development opportunities be improved, for instance by giving university teachers (more) access to selected parts of current research on UME, and possibly also participate in research and development projects? What initiatives exist, and which could be imagined as beneficial – both to increase the impact and quality of research on UME, and of UME itself

Serum 25(OH)D concentrations and atopic diseases at age 10: results from the GINIplus and LISAplus birth cohort studies

Background: Vitamin D is well recognized for its role in skeletal health and its involvement in the modulation of the immune system. In the literature, controversial results are reported for atopic diseases. Thus, we investigated the association between vitamin D status and the prevalence of atopic diseases. Methods: Serum 25-hydroxy-vitamin D (25(OH) D) concentrations were measured in a sample of 2815 10-years old children from two German birth cohort studies. Self-reported physician-diagnosed eczema, hay fever or allergic rhinitis, and asthma were used as outcome variables as well as specific IgE positivity against common allergens. We applied logistic regression models, deriving adjusted odds ratio estimates (aOR) and 95% confidence intervals (CI). Results: For asthma and hay fever or allergic rhinitis, no associations existed with serum 25(OH) D concentrations. We observed a significant positive relationship between serum 25(OH) D levels and eczema at age 10 (aOR = 1.09, CI = 1.01-1.17, per 10 nmol/l increase in serum 25(OH) D levels) and for the lifetime prevalence of eczema (aOR = 1.05, CI = 1.01-1.09). Specific IgE positivity for food allergens (aOR = 1.07, CI = 1.02-1.11) and aeroallergens (aOR = 1.05, CI = 1.01-1.08) at age 10, as well as lifetime prevalence, was significantly related to the vitamin D status. Conclusion: In this study we found no indication that higher blood 25(OH) D levels are associated with decreased risk for any of the atopic outcomes in children. However, we observed a positive association of serum 25(OH) D concentrations with eczema and detectable specific IgE. Due to the given limitations of our study, the clinical relevance of these findings needs further clarification

Association between dietary patterns and prediabetes, undetected diabetes or clinically diagnosed diabetes: results from the KORA FF4 study

Purpose Diet is one of the most important modifiable risk factors for the development of type 2 diabetes. Here, we aim to identify dietary patterns and to investigate their association with prediabetes, undetected diabetes and prevalent diabetes. Methods The present study included 1305 participants of the cross-sectional population-based KORA FF4 study. Oral glucose tolerance test (OGTT) measurements together with a physician-confirmed diagnosis allowed for an accurate categorization of the participants according to their glucose tolerance status into normal glucose tolerance (n = 698), prediabetes (n = 459), undetected diabetes (n = 49), and prevalent diabetes (n = 99). Dietary patterns were identified through principal component analysis followed by hierarchical clustering. The association between dietary patterns and glucose tolerance status was investigated using multinomial logistic regression models. Results A Prudent pattern, characterized by high consumption of vegetables, fruits, wholegrains and dairy products, and a Western pattern, characterized by high consumption of red and processed meat, alcoholic beverages, refined grains and sugar-sweetened beverages, were identified. Participants following the Western pattern had significantly higher chances of having prediabetes (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.35, 2.73), undetected diabetes (OR 10.12; 95% CI 4.19, 24.43) or prevalent diabetes (OR 3.51; 95% CI 1.85, 6.67), compared to participants following the Prudent pattern. Conclusion To our knowledge, the present study is one of the few investigating the association between dietary patterns and prediabetes or undetected diabetes. The use of a reference group exclusively including participants with normal glucose tolerance might explain the strong associations observed in our study. These results suggest a very important role of dietary habits in the prevention of prediabetes and type 2 diabetes