The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood

BackgroundGenetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2. In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients.MethodsA representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification.ResultsWe detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2-associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years.ConclusionsWe identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment

Empirická analýza sociálně-ekonomických důsledků strukturálních změn na trhu práce v Ostravě

Import 20/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Ekonomická fakulta. Katedra (156) makroekonomik

In Vivo Reporters for Visualizing Alternative Splicing of Hormonal Genes

Rapid progress in plant molecular biology in recent years has uncovered the main players in hormonal pathways and characterized transcriptomic networks associated with hormonal response. However, the role of RNA processing, in particular alternative splicing (AS), remains largely unexplored. Here, using example genes involved in cytokinin signaling, brassinosteroid synthesis and auxin transport, we present a set of reporters devised to visualize their AS events in vivo. These reporters show a differential tissue-specific expression of certain transcripts and reveal that expression of some of the them can be changed by the application of the exogenous hormone. Finally, based on the characterized AS event of the PIN7 auxin efflux carrier, we designed a system that allows a rapid genetic screening for the factors upstream of this AS event. Our innovative toolset can be therefore highly useful for exploring novel regulatory nodes of hormonal pathways and potentially helpful for plant researchers focusing on developmental aspects of AS

Application of Bonded Joints for Quantitative Analysis of Adhesion

The performance of hot-dip coated steel sheets is associated with properties of the zinc coatings on steel substrate. For the characterization of the adhesion behaviour of zinc coating on steel various tests were employed. The study was focused on quantification assessment of galvanized coating adhesion to substrates. Methods for evaluation of the bonding strength of zinc coating by the shear strength and the T-peel tests applying four special types of adhesives were used. The experimental tests of bonded joints show that the adhesion of the zinc coating to the substrate was higher than that of the applied adhesive with the highest strength

Silicon Actuates Poplar Calli Tolerance after Longer Exposure to Antimony

The presence of antimony (Sb) in high concentrations in the environment is recognized as an emerging problem worldwide. The toxicity of Sb in plant tissues is known; however, new methods of plant tolerance improvement must be addressed. Here, poplar callus (Populus alba L. var. pyramidallis) exposed to Sb(III) in 0.2 mM concentration and/or to silicon (Si) in 5 mM concentration was cultivated in vitro to determine the impact of Sb/Si interaction in the tissue. The Sb and Si uptake, growth, the activity of superoxide dismutase (SOD), catalase (CAT), guaiacol-peroxidase (G-POX), nutrient concentrations, and the concentrations of photosynthetic pigments were investigated. To elucidate the action of Si during the Sb-induced stress, the impact of short and long cultivations was determined. Silicon decreased the accumulation of Sb in the calli, regardless of the length of the cultivation (by approx. 34%). Antimony lowered the callus biomass (by approx. 37%) and decreased the concentrations of photosynthetic pigments (up to 78.5%) and nutrients in the tissue (up to 21.7%). Silicon supported the plant tolerance to Sb via the modification of antioxidant enzyme activity, which resulted in higher biomass production (increased by approx. 35%) and a higher uptake of nutrients from the media (increased by approx. 10%). Silicon aided the development of Sb-tolerance over the longer cultivation period. These results are key in understanding the action of Si-developed tolerance against metalloids

Effects of Exogenous Application of Indole-3-Butyric Acid on Maize Plants Cultivated in the Presence or Absence of Cadmium

Auxins are plant hormones that affect plant growth, development, and improve a plant’s tolerance to stress. In this study, we found that the application of indole-3-butyric acid (IBA) had diverse effects on the growth of maize (Zea mays L.) roots treated without/with Cd. IBA caused changes in the growth and morphology of the roots under non-stress conditions; hence, we were able to select two concentrations of IBA (10−11 M as stimulatory and 10−7 M as inhibitory). IBA in stimulatory concentration did not affect the concentration of H2O2 or the activity of antioxidant enzymes while IBA in inhibitory concentration increased only the concentration of H2O2 (40.6%). The application of IBA also affected the concentrations of mineral nutrients. IBA in stimulatory concentration increased the concentration of N, K, Ca, S, and Zn (5.8–14.8%) and in inhibitory concentration decreased concentration of P, K, Ca, S, Fe, Mn, Zn, and Cu (5.5–36.6%). Moreover, IBA in the concentration 10−9 M had the most positive effects on the plants cultivated with Cd. It decreased the concentration of H2O2 (34.3%), the activity of antioxidant enzymes (23.7–36.4%), and increased the concentration of all followed elements, except Mg (5.5–34.1%), when compared to the Cd

Alternative Models for Calculation of Static Overturning Angle and Lateral Stability Analysis of Subcompact and Universal Tractors

Vehicle lateral stability is evaluated using the static overturning angle. The correct value of this parameter depends on the calculation method. The aim of this study was to compare the latest standard with previously published methodology, to propose two alternative methodologies (Models 1 and 2) and to analyze the influence of various levels of rear wheel ballast weights and overall tire widths on the stability of universal and subcompact tractors. The results showed a significant regression effect of the rear wheel ballast weight on static overturning angle. The influence of the rear wheel ballast weight was higher in the subcompact tractor than in the universal tractor due to a larger distance between the height of the center of gravity and the center of the rear axle. Comparing the latest standard with the previously published methodology, the highest difference values were 13.82% and 7.30%. Both models are based on the previously published methodology and differ from each other in rolling and slope lines. The methodology proposed in Model 2 differed from the standard similarly to the previously published methodology; therefore, it is irrelevant. Model 1 reached differences of only −1.81% and −1.63%, representing a minimal difference from the standard

Frequency Spectra Analysis of Drawbar Pulls Generated by Special Driving Wheels Improving Tractive Performance

Driving wheel operation is characterized by force interactions with the ground, manifested in the form of vibrations. Signals generated by driving wheels can be analyzed in the frequency spectrum of tractor drawbar pull. The paper presents the analysis of a drawbar pull signal generated by a tractor equipped with two types of special driving wheels and standard tires. Beside the evaluation of special driving wheels’ properties according to drawbar power, the frequency spectra of measured signals were analyzed using a fast Fourier transformation. The model spectrum intervals for the standard tires, spike tires, and blade wheels were calculated according to the number of rubber lugs, blades, or spikes and compared with the experimental results. The results showed that the specific frequencies typical for blades and spikes were identified in model spectrum intervals. In the case of standard tires, the spectrum components typical for rubber lugs of the tire tread pattern were not identified. The highest amplitude of the typical frequency component was detected in the case of blades wheels, which showed the highest difference in drawbar power in comparison with the standard tires. Smaller dimensions of spikes resulted in lower amplitude and lower difference in drawbar power in comparison with the standard tires

EXO70A2 Is Critical for Exocyst Complex Function in Pollen Development

A pollen-specific component of the exocyst, a protein complex regulating cellular secretion, plays an important role in pollen development and function in Arabidopsis. Pollen development, pollen grain germination, and pollen tube elongation are crucial biological processes in angiosperm plants that need precise regulation to deliver sperm cells to ovules for fertilization. Highly polarized secretion at a growing pollen tube tip requires the exocyst tethering complex responsible for specific targeting of secretory vesicles to the plasma membrane. Here, we demonstrate that Arabidopsis (Arabidopsis thaliana) EXO70A2 (At5g52340) is the main exocyst EXO70 isoform in the male gametophyte, governing the conventional secretory function of the exocyst, analogous to EXO70A1 (At5g03540) in the sporophyte. Our analysis of a CRISPR-generated exo70a2 mutant revealed that EXO70A2 is essential for efficient pollen maturation, pollen grain germination, and pollen tube growth. GFP:EXO70A2 was localized to the nucleus and cytoplasm in developing pollen grains and later to the apical domain in growing pollen tube tips characterized by intensive exocytosis. Moreover, EXO70A2 could substitute for EXO70A1 function in the sporophyte, but not vice versa, indicating partial functional redundancy of these two closely related isoforms and higher specificity of EXO70A2 for pollen development-related processes. Phylogenetic analysis revealed that the ancient duplication of EXO70A, one of which is always highly expressed in pollen, occurred independently in monocots and dicots. In summary, EXO70A2 is a crucial component of the exocyst complex in Arabidopsis pollen that is required for efficient plant sexual reproduction

A Simple Risk Formula for the Prediction of COVID-19 Hospital Mortality

SARS-CoV-2 respiratory infection is associated with significant morbidity and mortality in hospitalized patients. We aimed to assess the risk factors for hospital mortality in non-vaccinated patients during the 2021 spring wave in the Czech Republic. A total of 991 patients hospitalized between January 2021 and March 2021 with a PCR-confirmed SARS-CoV-2 acute respiratory infection in two university hospitals and five rural hospitals were included in this analysis. After excluding patients with unknown outcomes, 790 patients entered the final analyses. Out of 790 patients included in the analysis, 282/790 (35.7%) patients died in the hospital; 162/790 (20.5) were male and 120/790 (15.2%) were female. There were 141/790 (18%) patients with mild, 461/790 (58.3%) with moderate, and 187/790 (23.7%) with severe courses of the disease based mainly on the oxygenation status. The best-performing multivariate regression model contains only two predictors—age and the patient’s state; both predictors were rendered significant (p < 0.0001). Both age and disease state are very significant predictors of hospital mortality. An increase in age by 10 years raises the risk of hospital mortality by a factor of 2.5, and a unit increase in the oxygenation status raises the risk of hospital mortality by a factor of 20