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Reversible protein phosphorylation regulates various cellular mechanisms in eukaryotes by altering the conformation, activity, localization, and stability of substrate proteins. In Arabidopsis thaliana root meristems, histone post-translational modifications are crucial for proper cell division, and they are also involved in oxidative stress signaling. To investigate the link between reactive oxygen species (ROS) and mitosis, we treated various Arabidopsis genotypes, including wild-types and mutants showing dysfunctional PP2A, with the ROS-inducing herbicide diquat (DQ). Studying the c3c4 double catalytic subunit mutant and fass regulatory subunit mutants of PP2A provided insights into phosphorylation-dependent mitotic processes. DQ treatment reduced mitotic activity in all genotypes and caused early mitotic arrest in PP2A mutants, likely due to oxidative stress-induced damage to essential mitotic processes. DQ had a minimal effect on reversible histone H3 phosphorylation in wild-type plants but significantly decreased phospho-histone H3 levels in PP2A mutants. Following drug treatment, the phosphatase activity decreased only in the stronger phenotype mutant plants (fass-5 and c3c4). Our findings demonstrate that (i) the studied PP2A loss-of-function mutants are more sensitive to increased intracellular ROS and (ii) DQ has indirect altering effects of mitotic activities and histone H3 phosphorylation. All these findings underscore the importance of PP2A in stress responses. [ABSTRACT FROM AUTHOR]

Primary demyelinating disorders of the central nervous system (CNS) include multiple sclerosis and the orphan conditions neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD). Curative technologies under development aim to selectively block autoimmune reactions against specific autoantigens while preserving the responsiveness of the immune system to other antigens. Our analysis focused on target patient selection for such developments, carefully considering the relevant clinical, regulatory, and market-related aspects. We found that the selection of patients with orphan conditions as target populations offers several advantages. Treatments for orphan conditions are associated with limited production capacity, qualify for regulatory incentives, and may require significantly shorter and lower-scale clinical programs. Furthermore, they may meet a higher acceptable cost-effectiveness threshold in order to compensate for the low numbers of patients to be treated. Finally, curative technologies targeting orphan indications could enter less competitive markets with lower risk of generic price erosion and would benefit from additional market protection measures available only for orphan products. These advantages position orphan conditions and subgroups as the most attractive target indications among primary demyelinating disorders of the CNS. The authors believe that after successful proof-of-principle demonstrations in orphan conditions, broader autoimmune patient populations may also benefit from the success of these pioneering developments. [ABSTRACT FROM AUTHOR]

Pertuzumab (Perjeta®), a humanized antibody binding to the dimerization arm of HER2 (Human epidermal growth factor receptor-2), has failed as a monotherapy agent in HER2 overexpressing malignancies. Since the molecular interaction of HER2 with ligand-bound EGFR (epidermal growth factor receptor) has been implied in mitogenic signaling and malignant proliferation, we hypothesized that this interaction, rather than HER2 expression and oligomerization alone, could be a potential molecular target and predictor of the efficacy of pertuzumab treatment. Therefore, we investigated static and dynamic interactions between HER2 and EGFR molecules upon EGF stimulus in the presence and absence of pertuzumab in HER2+ EGFR+ SK-BR-3 breast tumor cells using Förster resonance energy transfer (FRET) microscopy and fluorescence correlation and cross-correlation spectroscopy (FCS/FCCS). The consequential activation of signaling and changes in cell proliferation were measured by Western blotting and MTT assay. The autocorrelation functions of HER2 diffusion were best fitted by a three-component model corrected for triplet formation, and among these components the slowly diffusing membrane component revealed aggregation induced by EGFR ligand binding, as evidenced by photon-counting histograms and co-diffusing fractions. This aggregation has efficiently been prevented by pertuzumab treatment, which also inhibited the post-stimulus interaction of EGFR and HER2, as monitored by changes in FRET efficiency. Overall, the data demonstrated that pertuzumab, by hindering post-stimulus interaction between EGFR and HER2, inhibits EGFR-evoked HER2 aggregation and phosphorylation and leads to a dose-dependent decrease in cell proliferation, particularly when higher amounts of EGF are present. Consequently, we propose that EGFR expression on HER2-positive tumors could be taken into consideration as a potential biomarker when predicting the outcome of pertuzumab treatment. [ABSTRACT FROM AUTHOR]

The importance of highly monitored and analyzed processes, linked by information systems such as knowledge graphs, is growing. In addition, the integration of operators has become urgent due to their high costs and from a social point of view. An appropriate framework for implementing the Industry 5.0 approach requires effective data exchange in a highly complex manufacturing network to utilize resources and information. Furthermore, the continuous development of collaboration between human and machine actors is fundamental for industrial cyber-physical systems, as the workforce is one of the most agile and flexible manufacturing resources. This paper introduces the human-centric knowledge graph framework by adapting ontologies and standards to model the operator-related factors such as monitoring movements, working conditions, or collaborating with robots. It also presents graph-based data querying, visualization, and analysis through an industrial case study. The main contribution of this work is a knowledge graph-based framework that focuses on the work performed by the operator, including the evaluation of movements, collaboration with machines, ergonomics, and other conditions. In addition, the use of the framework is demonstrated in a complex use case based on an assembly line, with examples of resource allocation and comprehensive support in terms of the collaboration aspect between shop-floor workers. [ABSTRACT FROM AUTHOR]

Research Highlights: Scots pine (Pinus sylvestris L.) phenotypic plasticity will buffer and even benefit from temperature increases in Northeast Europe this century, except for the southern peripheries of the range. Objectives: The "stress test" aimed to assess the inherent potential of existing populations to withstand projected changes in their lifetimes at their original location. Materials and Methods: This study applied an alternative analytic approach to calculate response and transfer equations from historic height growth data from provenance tests in the former USSR and Hungary. Results: Contrary to earlier analyses, the populations displayed quasi-linear responses to mimicked warming without clear ecological optima, forecasting a general growth acceleration north of Lat. 53° N. Climate-triggered mortality is predicted for the near future in the southern peripheries. Locally adapted populations at the distribution confines of the northern and southern limits deserve special attention. Conclusions: The observed adaptability to warming moderates the necessity of genetic management interventions such as assisted migration. The support of natural processes of adaptation and acclimation will be sufficient in boreal and central Northeast Europe this century. Evacuating heat and drought-tolerant populations should be envisaged in the endangered zone to conserve valuable genetic resources. [ABSTRACT FROM AUTHOR]

We successfully created a composite photonic structure out of porous silicon (PSi) microcavities doped by the photochromic protein, photoactive yellow protein (PYP). Massive incorporation of the protein molecules into the pores was substantiated by a 30 nm shift of the resonance dip upon functionalization, and light-induced reflectance changes of the device due to the protein photocycle were recorded. Model calculations for the photonic properties of the device were consistent with earlier results on the nonlinear optical properties of the protein, whose degree of incorporation into the PSi structure was also estimated. The successful proof-of-concept results are discussed in light of possible practical applications in the future. [ABSTRACT FROM AUTHOR]

Background: There are recommendations for anticoagulation resumption after gastrointestinal bleeding (GIB), although data addressing this topic by direct oral anticoagulants (DOACs)-treated patients is lacking. We aim to determine the safety and efficacy of restarting DOACs after GIB. Methods: Studies that reported rebleeding, thromboembolic events, and mortality after restarting or withholding DOACs were selected. The systematic research was conducted in five databases (MEDLINE, EMBASE, CENTRAL, Web of Science, and Scopus). The random effect model was implemented to calculate the pooled odds ratio (OR). The ROBINS-I tool was used for risk of bias assessment, and the certainty of the evidence was evaluated with the GRADE approach. Results: Four retrospective cohort studies (1722 patients) were included in the meta-analysis. We did not find a significant increase in the risk of rebleeding in patients restarting DOACs after index GIB (OR = 1.12; 95% CI: 0.74–1.68). The outcomes of thromboembolic events and mortality data were not suitable for meta-analytic calculations. Single studies did not show statistically significant differences. Data quality assessment showed a serious overall risk of bias and very low quality of evidence (GRADE D). Conclusion: DOAC resumption after a GIB episode may not elevate the risk of rebleeding. However, the need for high-quality randomized clinical trials is crucial. [ABSTRACT FROM AUTHOR]

Lowland forests benefiting from groundwater availability are important ecosystems in Central Europe, both from ecological and economic perspectives. Besides a great reduction in their extent in the historical times and further shifts in the land use and water management regimes intensified during the industrial era, continuing changes in the groundwater and overall hydro-climatic conditions can pose significant challenges to them. Although tree-ring analyses serve as widely used tools to assess the climatic impact on tree growth and vitality, few studies have attempted to investigate the effects of subsurface hydrology on interannual fluctuations in xylem production. In this study, we compared the tree-ring width series of pedunculate oak (Quercus robur L.) from a forested area in southwestern Hungary with the time series of monthly groundwater depth and climatic variables over the period of 1920–2017 with a specific focus on 1961–2017. The radial growth of the studied trees showed the strongest relationship with late winter and early spring groundwater and drought conditions preceding the growing season, differing from the commonly reported climatic signals marked by early summer meteorological conditions of the vegetation season. The results suggest that the groundwater recharge during the dormant period preceding the vegetation season and the groundwater levels in early spring were among the key limiting factors on tree growth in the study area. In the growing years starting with a sufficiently high groundwater table, even scarce summer precipitation did not seem to limit radial growth drastically. However, unfavorable shifts in climatic conditions during the past few decades and the associated uncertainties in the future groundwater regime imply that additional active measures aimed at maintaining and restoring groundwater conditions may well be highly beneficial for sustaining groundwater-dependent forest ecosystems and their productivity. [ABSTRACT FROM AUTHOR]

Assembly line balancing improves the efficiency of production systems by the optimal assignment of tasks to operators. The optimisation of this assignment requires models that provide information about the activity times, constraints and costs of the assignments. A multilayer network-based representation of the assembly line-balancing problem is proposed, in which the layers of the network represent the skills of the operators, the tools required for their activities and the precedence constraints of their activities. The activity–operator network layer is designed by a multi-objective optimisation algorithm in which the training and equipment costs as well as the precedence of the activities are also taken into account. As these costs are difficult to evaluate, the analytic hierarchy process (AHP) technique is used to quantify the importance of the criteria. The optimisation problem is solved by a multi-level simulated annealing algorithm (SA) that efficiently handles the precedence constraints. The efficiency of the method is demonstrated by a case study from wire harness manufacturing. [ABSTRACT FROM AUTHOR]

This paper introduces a spectral clustering-based method to show that stock prices contain not only firm but also network-level information. We cluster different stock indices and reconstruct the equity index graph from historical daily closing prices. We show that tail events have a minor effect on the equity index structure. Moreover, covariance and Shannon entropy do not provide enough information about the network. However, Gaussian clusters can explain a substantial part of the total variance. In addition, cluster-wise regressions provide significant and stationer results. [ABSTRACT FROM AUTHOR]

Photosynthetic reaction center proteins (RCs) are the most efficient light energy converter systems in nature. The first steps of the primary charge separation in photosynthesis take place in these proteins. Due to their unique properties, combining RCs with nano-structures promising applications can be predicted in optoelectronic systems. In the present work RCs purified from Rhodobacter sphaeroides purple bacteria were immobilized on multiwalled carbon nanotubes (CNTs). Carboxyl—and amine-functionalised CNTs were used, so different binding procedures, physical sorption and chemical sorption as well, could be applied as immobilization techniques. Light-induced singlet oxygen production was measured in the prepared photoactive biocomposites in water-based suspension by histidine mediated chemical trapping. Carbon nanotubes were applied under different conditions in order to understand their role in the equilibration of singlet oxygen concentration in the suspension. CNTs acted as effective quenchers of 1O2 either by physical (resonance) energy transfer or by chemical (oxidation) reaction and their efficiency showed dependence on the diffusion distance of 1O2. [ABSTRACT FROM AUTHOR]

The feasibility of the application of the Photo-Fenton process in the treatment of aqueous solution contaminated by Tylosin antibiotic was evaluated. The Response Surface Methodology (RSM) based on Central Composite Design (CCD) was used to evaluate and optimize the effect of hydrogen peroxide, ferrous ion concentration and initial pH as independent variables on the total organic carbon (TOC) removal as the response function. The interaction effects and optimal parameters were obtained by using MODDE software. The significance of the independent variables and their interactions was tested by means of analysis of variance (ANOVA) with a 95% confidence level. Results show that the concentration of the ferrous ion and pH were the main parameters affecting TOC removal, while peroxide concentration had a slight effect on the reaction. The optimum operating conditions to achieve maximum TOC removal were determined. The model prediction for maximum TOC removal was compared to the experimental result at optimal operating conditions. A good agreement between the model prediction and experimental results confirms the soundness of the developed model. [ABSTRACT FROM AUTHOR]

The boletoid genera Butyriboletus and Exsudoporus have recently been suggested by some researchers to constitute a single genus, and Exsudoporus was merged into Butyriboletus as a later synonym. However, no convincing arguments have yet provided significant evidence for this congeneric placement. In this study, we analyze material from Exsudoporus species and closely related taxa to assess taxonomic and phylogenetic boundaries between these genera and to clarify species delimitation within Exsudoporus. Outcomes from a multilocus phylogenetic analysis (ITS, nrLSU, tef1-α and rpb2) clearly resolve Exsudoporus as a monophyletic, homogenous and independent genus that is sister to Butyriboletus. An accurate morphological description, comprehensive sampling, type studies, line drawings and a historical overview on the nomenclatural issues of the type species E. permagnificus are provided. Furthermore, this species is documented for the first time from Israel in association with Quercus calliprinos. The previously described North American species Exsudoporus frostii and E. floridanus are molecularly confirmed as representatives of Exsudoporus, and E. floridanus is epitypified. The eastern Asian species Leccinum rubrum is assigned here to Exsudoporus based on molecular evidence, and a new combination is proposed. Sequence data from the original material of the Japanese Boletus kermesinus were generated, and its conspecificity with L. rubrum is inferred as formerly presumed based on morphology. Four additional cryptic species from North and Central America previously misdetermined as either B. frostii or B. floridanus are phylogenetically placed but remain undescribed due to the paucity of available material. Boletus weberi (syn. B. pseudofrostii) and Xerocomus cf. mcrobbii cluster outside of Exsudoporus and are herein assigned to the recently described genus Amoenoboletus. Biogeographic distribution patterns are elucidated, and a dichotomous key to all known species of Exsudoporus worldwide is presented. [ABSTRACT FROM AUTHOR]

Semi-intensive common carp (Cyprinus carpio) farm technology uses several feed types affecting the growth performance; however, we know less about their long-term effects on water quality. Herein, we evaluated the effects of three commonly used feeds—moderate levels of fish meal and fish oil feed (FF), plant meal and plant oil feed (PF), and cereal feed (CF) on the nutrient (total nitrogen (TN), total phosphorus (TP) and organic matter (OM)) content of the pond water. The experiment was carried out over three consecutive years from juveniles to market-sized fish. The type of feed affected the net yields, but generally, it did not affect the water quality. The year of sampling, however, was a significant factor affecting TN, TP, and OM, whose concentrations decreased during the three years. Our findings highlight that the age of the stocked fish on water quality has a more pronounced effect than the nutrient profile of the supplementary feed. Additionally, the plant-based feed could provide comparable net yields as the fish meal-based feed without additional nutrient loading in the water column, reinforcing the sustainability of alternative feeds in semi-intensive carp farming. [ABSTRACT FROM AUTHOR]

Background. Cerebral thromboembolism is a rare but feared complication of transcatheter ablation in patients with atrial fibrillation (AF). Here, we aimed to test which pre-procedural anticoagulation strategy results in less intracardiac activation of hemostasis during ablation. Patients and methods. In this observational study, 54 paroxysmal/persistent AF patients undergoing cryoballoon ablation were grouped according to their periprocedural anticoagulation strategy: no anticoagulation (oral anticoagulation (OAC) free; n = 24), uninterrupted vitamin K antagonists (VKA) (n = 11), uninterrupted dabigatran (n = 17). Blood was drawn from the left atrium before and immediately after the ablation procedure. Cryoablations were performed according to standard protocols, during which heparin was administered. Heparin-insensitive markers of hemostasis and endothelial damage were tested from intracardiac samples: D-dimer, quantitative fibrin monomer (FM), plasmin-antiplasmin complex (PAP), von Willebrand factor (VWF) antigen, chromogenic factor VIII (FVIII) activity. Results. D-dimer increased significantly in all groups post-ablation, with lowest levels in the dabigatran group (median [interquartile range]: 0.27 [0.36] vs. 1.09 [1.30] and 0.74 [0.26] mg/L in OAC free and uninterrupted VKA groups, respectively, p < 0.001). PAP levels were parallel to this observation. Post-ablation FM levels were elevated in OAC free (26.34 [30.04] mg/L) and VKA groups (10.12 [16.01] mg/L), but remained below cut-off in all patients on dabigatran (3.98 [2.0] mg/L; p < 0.001). VWF antigen and FVIII activity increased similarly post-ablation in all groups, suggesting comparable procedure-related endothelial damage. Conclusion. Dabigatran provides greater inhibition against intracardiac activation of hemostasis as compared to VKAs during cryoballoon catheter ablation. [ABSTRACT FROM AUTHOR]

With the intensification of aquaculture, the structure and dynamics of aquatic ecosystems are highly affected. At the same time, for a pond fish farmer, one of the most important tasks is to establish and maintain stable and favourable zooplankton populations. In this paper, we assess the effects of different supplementary feed types on zooplankton communities in freshwater fishponds. In an outdoor, experimental fishpond system, carp individuals of 2+ years of age were stocked and fed with either a fishmeal-based diet (FF), a plant meal containing experimental feed (PF) or cereals (CT). To compare the diversity of the zooplankton communities, we used the Shannon diversity index, and to assess the effects of environmental factors and the feed ingredients, we applied canonical correspondence analysis. We described the dynamics of zooplankton communities, where the biodiversity of rotifera and Crustacean communities showed temporal differences. In order to examine the effects of feed ingredients, temporal clustering was applied. The different diets did not consistently alter the composition of zooplankton communities. Consequently, the plant meal containing experimental feed had no negative effect on the planktonic biodiversity, which makes it suitable as an alternative feed source for fishponds at the applied level. [ABSTRACT FROM AUTHOR]

With the intensification of aquaculture technologies, the amount of feed input and waste material is increasing, creating potentially negative impacts on freshwater habitats receiving effluent from such systems. Changes in biodiversity of zooplankton communities is often used to assess the effects of such impacts. Rotifers are suitable for bioindication of water quality due to their fast reaction to environmental changes. We examined seasonal changes in the diversity of rotifer communities along a 3.5 km section of the biggest oxbow lake in the Tisza River basin, Hungary, that received inflow from an intensive tank-based aquaculture farm. We detected a species-rich rotifer community with 26 species. Using the Rényi one-parameter diversity index families, we found that biodiversity increased away from the point of inflow in spring, but after a summer transition period the situation became partially reversed during autumn. At the beginning of the study period, the nutrient-rich effluent strengthened the dominance of common species, which decreased but did not disappear in summer. In autumn, the extra nutrient input delayed the decline of the rotifer community at the point of effluent. [ABSTRACT FROM AUTHOR]

Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to enhance their own phagocytic capacity by upregulating several phagocytic genes. Our data indicated that these retinoids might be dihydroretinoids, which are products of the retinol saturase (RetSat) pathway. In the present study, the efferocytosis of RetSat-null mice was investigated. We show that among the retinoid-sensitive phagocytic genes, only transglutaminase 2 responded in macrophages and in differentiating monocytes to dihydroretinol. Administration of dihydroretinol did not affect the expression of the tested genes differently between differentiating wild type and RetSat-null monocytes, despite the fact that the expression of RetSat was induced. However, in the absence of RetSat, the expression of numerous differentiation-related genes was altered. Among these, impaired production of MFG-E8, a protein that bridges apoptotic cells to the αvβ3/β5 integrin receptors of macrophages, resulted in impaired efferocytosis, very likely causing the development of mild autoimmunity in aged female mice. Our data indicate that RetSat affects monocyte/macrophage differentiation independently of its capability to produce dihydroretinol at this stage. [ABSTRACT FROM AUTHOR]

Photosynthetic reaction center proteins (RCs) are the most efficient light energy converter systems in nature. The first steps of the primary charge separation in photosynthesis take place in these proteins. Due to their unique properties, combining RCs with nano-structures promising applications can be predicted in optoelectronic systems. In the present work RCs purified from Rhodobacter sphaeroides purple bacteria were immobilized on multiwalled carbon nanotubes (CNTs). Carboxyl-and amine-functionalised CNTs were used, so different binding procedures, physical sorption and chemical sorption as well, could be applied as immobilization techniques. Light-induced singlet oxygen production was measured in the prepared photoactive biocomposites in water-based suspension by histidine mediated chemical trapping. Carbon nanotubes were applied under different conditions in order to understand their role in the equilibration of singlet oxygen concentration in the suspension. CNTs acted as effective quenchers of ¹O₂ either by physical (resonance) energy transfer or by chemical (oxidation) reaction and their efficiency showed dependence on the diffusion distance of ¹O₂., Competing Interests: The authors declare no conflict of interest.