Search

Here we describe the role of the Cladosporium fulvum nitrogen response factor 1 (Nrf1) gene in regulation of the expression of avirulence gene Avr9 and virulence on tomato. The Nrf1 gene, which was isolated by a polymerase chain reaction-based strategy, is predicted to encode a protein of 918 amino acid residues. The protein contains a putative zinc finger DNA-binding domain that shares 98% amino acid identity with the zinc finger of the major nitrogen regulatory proteins AREA and NIT2 of Aspergillus nidulans and Neurospora crassa, respectively. Functional equivalence of Nrf1 to areA was demonstrated by complementation of an A. nidulans areA loss-of-function mutant with Nrf1. Nrf1-deficient transformants of C. fulvum obtained by homologous recombination were unable to utilize nitrate and nitrite as a nitrogen source. In contrast to what was observed in the C. fulvum wild-type, the Avr9 gene was no longer induced under nitrogen-starvation conditions in Nrf1-deficient strains. On susceptible tomato plants, the Nrf1-deficient strains were as virulent as wild-type strains of C. fulvum, although the expression of the Avr9 gene was strongly reduced. In addition, Nrf1-deficient strains were still avirulent on tomato plants containing the functional Cf-9 resistance gene, indicating that in planta, apparently sufficient quantities of stable AVR9 elicitor are produced. Our results suggest that the NRF1 protein is a major regulator of the Avr9 gene.

Abstract We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR deficiency as detected by RAD51 foci formation. This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.

A meningioma is a rare primary CNS tumor that tends to present more so in females in a slowly progressive fashion. The cavernous sinus and cerebellopontine angle are uncommon locations for meningiomas. We present a case of a meningioma in a 60-year-old female presenting to the emergency department for a sudden onset headache, vertigo, facial paresthesias, and chest pain. Inpatient workup revealed orthostatic hypotension, a meningioma spanning from the left cavernous sinus to the left cerebellopontine angle encasing the left cavernous internal carotid artery on MRI and CTA, and an incidental 12 mm calcified fibroadenoma on CT. Hospital course consisted of supportive treatment, physical rehabilitation, and review of previous imaging to determine need for intervention per consultants’ recommendations. The patient was discharged with an antiplatelet, an antihistamine, appropriate additional medications, a vestibular therapy script, and outpatient referrals for a decision regarding surveillance and intervention. Overall, this case describes some key points. It demonstrates that cavernous sinus and cerebellopontine angle meningiomas can occur simultaneously, especially as a continuous mass, which very few cases have done so far. It also highlights an acute clinical presentation of a meningioma, contrary to the gradually progressive one observed in most instances. Last, but not least, it shows how nonspecific symptoms can lead to unique findings at times.

Abstract Background In order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity. Methods Based on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups. Results Compared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p

Abstract Self-sufficiency, climate change and increasing geopolitical risks have driven energy policies to make renewable energy sources dominant in the power production portfolios. The initial boom in the mid-2000s of global photovoltaic installations demonstrated the feasibility of the ambitious renewable energy targets. However, this rapid scale-up has introduced challenges, including price volatility and system integration issues. This communication calls the attention to these emerging challenges and offers quantitative insights on how rapid adoption of a more diversified photovoltaics deployment strategies can mitigate price volatilities, reduce fossil fuel dependence and steer Europe towards a forward-thinking sustainable energy pathway. The analysis reveals that as innovative bifacial photovoltaic systems are incorporated on a large-scale disruptive scenario, four main patterns emerge: economic value of solar production increases, base-load electricity price decreases, sun-rich countries expand their solar contributions, whereas nations with ample grid interconnections enhance their energy imports from neighbouring countries. It also underscores the importance of maintaining photovoltaics an attractive option for energy investors and traders in the future. Establishing this groundwork is critical since a successful integration of large-scale solar systems contributing to decrease price volatilities in Europe and US will carry significant repercussions for global energy policy formulation.

Abstract Background Extraneural metastasis of central nervous system tumors is generally rare and most often reported in glioblastomas and medulloblastomas, whereas oligodendrogliomas seem to have the lowest risk of extracranial metastasis. Given its infrequent occurrence, both the diagnosis and therapy of metastatic oligodendroglioma is often challenging. Case presentation This case study presents an oligodendroglioma, the isocitrate dehydrogenase 1 (IDH1) mutant, 1p/19q-codeleted tumor with bone marrow metastasis. The significance of this case lies in the comprehensive molecular analysis conducted for both the primary tumor and the metastasis. Chromosome 7 trisomy and chromosome 10 monosomy (+ 7/-10) were detected in the metastasis indicating molecular progression, which, to the best of our knowledge, has not been previously documented in metastatic oligodendroglioma. Conclusions This case study serves additional information for better understanding of the metastatic capabilities of CNS tumors.

Abstract Aquatic macrophytes form a three dimensional complex structure in the littoral zones of lakes, with many physical, chemical and biological gradients and interactions. This special habitat harbours a unique microalgal assemblage called metaphyton, that differs both from the phytoplankton of the pelagial and from the benthic assemblages whose elements are tightly attached to the substrates. Since metaphytic assemblages significantly contribute to the diversity of lakes’ phytoplankton, it is crucial to understand and disentangle those mechanisms that ensure their development. Therefore, we focused on the question of how a single solid physical structure contribute to maintaining metaphytic assemblages. Using a laboratory experiment we studied the floristic and functional differences of microalgal assemblages in microcosms that simulated the conditions that an open water, a complex natural macrophyte stand (Utricularia vulgaris L.), or an artificial substrate (cotton wool) provide for them. We inoculated the systems with a species rich (> 326 species) microalgal assemblage collected from a eutrophic oxbow lake, and studied the diversity, trait and functional group composition of the assemblages in a 24 day long experimental period. We found that both natural and artificial substrates ensured higher species richness than the open water environment. Functional richness in the open water environment was lower than in the aquaria containing natural macrophyte stand but higher than in which cotton wool was placed. This means that the artificial physical structure enhanced functional redundancy of the resident functional groups. Elongation measures of microalgal assemblages showed the highest variation in the microcosms that simulated the open water environment. Our results suggest that assembly of metaphytic algal communities is not a random process, instead a deterministic one driven by the niche characteristics of the complex three dimensional structure created by the stands of aquatic macrophytes.

Exact knowledge of wind energy potential is a fundamental issue in wind energy utilization. The vertical changes in wind speeds, that is, the wind profile, have a predominant impact on the wind energy available at a location because the kinetic energy of moving air is proportional to the square of the wind speed. Roughness describes the resistance of a 3D surface to moving air. The exponent α of the power law of Hellmann and the roughness length (z0) are two parameters that describe the effects of the roughness of the surface on the wind profile. They can be used for the vertical extrapolation of wind speeds. The exponent α can be determined using multiple height level wind speed measurement data, whereas a reliable technique for the calculation of the roughness length requires detailed knowledge of the 3D geometry of the measurement site. In the present study, the exponent α was calculated based on SODAR wind speed measurements, while (z0) was determined using a combination of GIS and UAS-based aerial survey methods. Wind speeds measured at 50 m were extrapolated for height levels of 80, 90, 100, 110, and 120 m using dynamic power law exponent values. Wind power was determined using the power law (method V1), roughness length (method V2), frequency distribution (method W-RF), and gamma distribution (method W-G), and Windographer software was compared to the values calculated from the empirical (measured) wind speeds. A comparative statistical analysis of the datasets of the power law and roughness length methods on monthly/diurnal, annual/diurnal, and month/direction contexts showed no significant differences at all height levels. Differences can be detected in the distribution of the signs of the differences at heights of 80 and 120 m for the entire dataset. Underestimation was dominant with a significant frequency (over 70 %) in the case of both methods and heights. There were no significant differences between the wind power estimations provided by the different methods, and all the methods involved in the study underestimated the wind speeds and wind energy potential for each height level. Methods V1 and V2 can be used alternatively, depending on the input data available for analysis. The major advantage of method V2 is that it provides the same accuracy as V1, which requires a UAS-based aerial survey at the beginning, but continuous wind measurements must be performed at a lower height only. This means that there is no need for a high measurement tower, which makes the measurements simpler, more cost-effective, and causes much less disturbance to the environment. Another important advantage of the methods presented here is that they use a dynamic approach of power law exponent values that provide a more realistic estimation of wind speed and energy on a diurnal scale.

Abstract Background In last two decades, the use of high-throughput sequencing technologies has accelerated the pace of discovery of proteins. However, due to the time and resource limitations of rigorous experimental functional characterization, the functions of a vast majority of them remain unknown. As a result, computational methods offering accurate, fast and large-scale assignment of functions to new and previously unannotated proteins are sought after. Leveraging the underlying associations between the multiplicity of features that describe proteins could reveal functional insights into the diverse roles of proteins and improve performance on the automatic function prediction task. Results We present GO-LTR, a multi-view multi-label prediction model that relies on a high-order tensor approximation of model weights combined with non-linear activation functions. The model is capable of learning high-order relationships between multiple input views representing the proteins and predicting high-dimensional multi-label output consisting of protein functional categories. We demonstrate the competitiveness of our method on various performance measures. Experiments show that GO-LTR learns polynomial combinations between different protein features, resulting in improved performance. Additional investigations establish GO-LTR’s practical potential in assigning functions to proteins under diverse challenging scenarios: very low sequence similarity to previously observed sequences, rarely observed and highly specific terms in the gene ontology. Implementation The code and data used for training GO-LTR is available at https://github.com/aalto-ics-kepaco/GO-LTR-prediction .

Abstract Homologous recombination (HR) and nucleotide excision repair (NER) are the two most frequently disabled DNA repair pathways in cancer. HR-deficient breast, ovarian, pancreatic and prostate cancers respond well to platinum chemotherapy and PARP inhibitors. However, the frequency of HR deficiency in gastric and esophageal adenocarcinoma (GEA) still lacks diagnostic and functional validation. Using whole exome and genome sequencing data, we found that a significant subset of GEA, but very few colorectal adenocarcinomas, show evidence of HR deficiency by mutational signature analysis (HRD score). High HRD gastric cancer cell lines demonstrated functional HR deficiency by RAD51 foci assay and increased sensitivity to platinum chemotherapy and PARP inhibitors. Of clinical relevance, analysis of three different GEA patient cohorts demonstrated that platinum treated HR deficient cancers had better outcomes. A gastric cancer cell line with strong sensitivity to cisplatin showed HR proficiency but exhibited NER deficiency by two photoproduct repair assays. Single-cell RNA-sequencing revealed that, in addition to inducing apoptosis, cisplatin treatment triggered ferroptosis in a NER-deficient gastric cancer, validated by intracellular GSH assay. Overall, our study provides preclinical evidence that a subset of GEAs harbor genomic features of HR and NER deficiency and may therefore benefit from platinum chemotherapy and PARP inhibitors.

Abstract Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators of these key cellular programs, we engineer a dual endogenous reporter system by genome-editing the SOX9 and KRT20 loci of human CRC cell lines to express fluorescent reporters, broadcasting aberrant stem cell-like and differentiation activity, respectively. By applying a CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs to this platform, we identify factors that contribute to stem cell-like activity and differentiation in CRC. Perturbation single cell RNA sequencing (Perturb-seq) of validated hits nominate SMARCB1 of the BAF complex (also known as SWI/SNF) as a negative regulator of differentiation across an array of neoplastic colon models. SMARCB1 is a dependency and required for in vivo growth of human CRC models. These studies highlight the utility of biologically designed endogenous reporter platforms to uncover regulators with therapeutic potential.

Background: Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Antibiotic stewardship program (ASP) has been implemented to improve rational and responsible antibiotic use by encouraging guideline adherence.Objective: This retrospective observational before–after study aimed to evaluate whether the ASP may improve guideline adherence, antibiotic exposure, and clinical outcomes in patients hospitalized due to CAP in Hungary.Methods: The study was conducted at a pulmonology department of a tertiary care medical center in Hungary. The ASP implementation consisted of written and published guidelines available to all professionals, continuous supervision, and counseling services on antibiotic therapies at an individual level, with the aim of ensuring compliance with CAP guidelines. Overall guideline adherence (agent selection, route of administration, and dose), clinical outcomes (length of stay and 30-day mortality), antibiotic exposure, and direct costs were compared between the two periods. Fisher’s exact test and t-test were applied to compare categorical and continuous variables, respectively. P-values below 0.05 were defined as significant.Results: Significant improvement in overall CAP guideline adherence (30.2%), sequential therapy (10.5%), and a significant reduction in the total duration of antibiotic therapy (13.5%) were observed. Guideline non-adherent combination therapies with metronidazole decreased significantly by 28.1%. Antibiotic exposure decreased by 7.2%, leading to a significant decrease in direct costs (23.6%). Moreover, the ASP had benefits for clinical outcomes, and length of stay decreased by 13.5%.Conclusion: The ASP may play an important role in optimizing empirical antibiotic therapy in CAP having a sustained long-term effect.

Considering the importance of body composition and lower-body strength and power for basketball players' on-court performance, as well as a lack of sports science research focused on female athletes, the purpose of the present investigation was to record the anthropometric and countermovement vertical jump (CMJ) characteristics of top-tier U16 and U18 female basketball players and examine between-group differences in the aforementioned tests. Thirty-two athletes who were a part of the national basketball academy volunteered to participate in the present investigation. Following the body composition assessment conducted via a segmental multifrequency bioimpedance analyzer, athletes performed three CMJs while standing on a force plate system sampling at 1000 Hz. Independent t-test and Mann-Whitney U-test were used to examine between-group differences. The findings reveal significant differences in body composition and lower-body neuromuscular performance characteristics between female basketball players ages 16 and 18. Although no differences were observed in muscle and body fat percentages, the U18 group had significantly greater height, overall body mass (both muscle and fat mass), as well as greater segmental fat-free mass (trunk, both legs and arms), intracellular and extracellular water, and body mass index when compared to their U16 counterparts. On the other hand, the U18 group demonstrated longer eccentric, concentric, and braking phase duration, as well as overall contraction time when compared to the U16 players. In addition, the U18 athletes exhibited higher eccentric mean force and power, concentric impulse, peak power, and mean and peak force.

In recent years, large language models (LLMs) have achieved remarkable success in natural language processing (NLP). LLMs require an extreme amount of parameters to attain high performance. As models grow into the trillion-parameter range, computational and memory costs increase significantly. This makes it difficult for many researchers to access the resources needed to train or apply these models. Optimizing LLM performance involves two main approaches: fine-tuning pre-trained models for specific tasks to achieve state-of-the-art performance, and reducing costs or improving training time while maintaining similar performance. This paper presents a systematic literature review (SLR) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We reviewed 65 publications out of 983 from 2017 to December 2023, retrieved from 5 databases. The study presents methods to optimize and accelerate LLMs while achieving cutting-edge results without sacrificing accuracy. We begin with an overview of the development of language modeling, followed by a detailed explanation of commonly used frameworks and libraries, and a taxonomy for improving and speeding up LLMs based on three classes: LLM training, LLM inference, and system serving. We then delve into recent optimization and acceleration strategies such as training optimization, hardware optimization, scalability and reliability, accompanied by the taxonomy and categorization of these strategies. Finally, we provide an in-depth comparison of each class and strategy, with two case studies on optimizing model training and enhancing inference efficiency. These case studies showcase practical approaches to address LLM resource limitations while maintaining performance.

Abstract Ageing is often characterised by progressive accumulation of damage, and it is one of the most important risk factors for chronic disease development. Epigenetic mechanisms including DNA methylation could functionally contribute to organismal aging, however the key functions and biological processes may govern ageing are still not understood. Although age predictors called epigenetic clocks can accurately estimate the biological age of an individual based on cellular DNA methylation, their models have limited ability to explain the prediction algorithm behind and underlying key biological processes controlling ageing. Here we present XAI-AGE, a biologically informed, explainable deep neural network model for accurate biological age prediction across multiple tissue types. We show that XAI-AGE outperforms the first-generation age predictors and achieves similar results to deep learning-based models, while opening up the possibility to infer biologically meaningful insights of the activity of pathways and other abstract biological processes directly from the model.

Abstract Cognitive decline is a major health concern and identification of genes that may serve as drug targets to slow decline is important to adequately support an aging population. Whilst genetic studies of cross-sectional cognition have been carried out, cognitive change is less well-understood. Here, using data from the TOMMORROW trial, we investigate genetic associations with cognitive change in a cognitively normal older cohort. We conducted a genome-wide association study of trajectories of repeated cognitive measures (using generalised estimating equation (GEE) modelling) and tested associations with polygenic risk scores (PRS) of potential risk factors. We identified two genetic variants associated with change in attention domain scores, rs534221751 (p = 1 × 10−8 with slope 1) and rs34743896 (p = 5 × 10−10 with slope 2), implicating NCAM2 and CRIPT/ATP6V1E2 genes, respectively. We also found evidence for the association between an education PRS and baseline cognition (at >65 years of age), particularly in the language domain. We demonstrate the feasibility of conducting GWAS of cognitive change using GEE modelling and our results suggest that there may be novel genetic associations for cognitive change that have not previously been associated with cross-sectional cognition. We also show the importance of the education PRS on cognition much later in life. These findings warrant further investigation and demonstrate the potential value of using trial data and trajectory modelling to identify genetic variants associated with cognitive change.

Background/Objectives: Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism exerting protection against atherosclerosis by multiple actions on the blood vessels, liver, and adipose tissues. We aimed to investigate serum FGF21 level and its relation to thyroid hormones and metabolic parameters among patients with Hashimoto’s thyroiditis (HT). Methods: Eighty patients with HT on levothyroxine treatment and eighty-two age- and BMI-matched adults without thyroid disease serving as controls were enrolled. Serum FGF21 concentrations were determined with an enzyme-linked immunosorbent assay. Results: Median serum FGF21 level was significantly lower in HT patients compared with controls (74.2 (33.4–148.3) pg/mL vs. 131.9 (44.8–236.3) pg/mL; p = 0.03). We found a positive correlation between FGF21 and age, triglyceride, total cholesterol, and low-density lipoprotein cholesterol in both groups, while thyroid stimulating hormone and C-reactive protein showed a positive correlation, and thyroxine had an inverse correlation with FGF21 only in control subjects. According to multiple regression analyses, thyroid status is the main predictor of FGF21 in healthy controls, while it is not a significant predictor of FGF21 among HT patients on levothyroxine supplementation therapy. Conclusions: Our results indicate that the physiological role of thyroid function in the regulation of FGF21 synthesis is impaired in HT patients, which may contribute to the metabolic alterations characteristic of HT patients.

Potassium ferrate(VI) (K2FeO4) as a particularly strong oxidant represents an effective and environmentally friendly waste water treatment material. When produced by anodic oxidation in highly alkaline aqueous solution, the K2FeO4 product is separated and sealed in inert plastic bags with the retention of some liquid phase with high pH. This method proved to be excellent for long-term storage at moderately low temperature (5 °C) for industrial applications. It is still imperative to check the ferrate(VI) content of the product whenever it is to be used. Fe-57 Mössbauer spectroscopy is an excellent tool for checking the ratio of ferrate(VI) to the degradation product iron(III) in a sample. For this purpose, normally the spectral areas of the corresponding subspectra are considered; however, this approximation neglects the possible differences in the corresponding Mössbauer–Lamb factors. In this work, we have successfully determined the Mössbauer–Lamb factors for the ferrate(VI) and for the most common iron(III) degradation products observed. We have found superparamagnetic behavior and low-temperature phase transformation for another iron(III) degradation product that made the determination of the Mössbauer–Lamb factors impossible in that case. The identities of a total of three different iron(III) degradation products have been confirmed.

Sprint performance is commonly assessed via discrete sprint tests and analyzed through kinematic estimates modeled using a mono-exponential equation, including estimated maximal sprinting speed (MSS), relative acceleration (TAU), maximum acceleration (MAC), and relative propulsive maximal power (PMAX). The acceleration–velocity profile (AVP) provides a simple summary of short sprint performance using two parameters: MSS and MAC, which are useful for simplifying descriptions of sprint performance, comparison between athletes and groups of athletes, and estimating changes in performance over time or due to training intervention. However, discrete testing poses logistical challenges and defines an athlete’s AVP exclusively from the performance achieved in an isolated testing environment. Recently, an in situ AVP (velocity–acceleration method) was proposed to estimate kinematic parameters from velocity and acceleration data obtained via global or local positioning systems (GPS/LPS) over multiple training sessions, plausibly improving the time efficiency of sprint monitoring and increasing the sample size that defines the athlete’s AVP. However, the validity and sensitivity of estimates derived from the velocity–acceleration method in relation to changes in criterion scores remain elusive. To assess the concurrent validity and sensitivity of kinematic measures from the velocity–acceleration method, 31 elite youth basketball athletes (23 males and 8 females) completed two maximal effort 30 m sprint trials. Performance was simultaneously measured by a laser gun and an LPS (Kinexon), with kinematic parameters estimated using the time–velocity and velocity–acceleration methods. Agreement (%Bias) between laser gun and LPS-derived estimates was within the practically significant magnitude (±5%), while confidence intervals for the percentage mean absolute difference (%MAD) overlapped practical significance for TAU, MAC, and PMAX using the velocity–acceleration method. Only the MSS parameter showed a sensitivity (%MDC95) within practical significance (10%) for both the time–velocity and velocity–acceleration methods. Thus, sports practitioners may be confident in the concurrent validity and sensitivity of MSS estimates derived in situ using the velocity–acceleration method, while caution should be applied when using this method to infer an athlete’s maximal acceleration capabilities.

In Nigeria, 86 million people lack electricity access, the highest number worldwide, predominantly in rural areas. Despite government efforts, constrained budgets necessitate private investors, who, without adequate incentives, are hesitant to commit capital due to perceived high risks. This study identifies three existing incentive policies—concessionary loans, capital subsidy, and financing productive use equipment—aimed at promoting rural electrification in Nigeria. Employing geospatial and regulatory analyses, we evaluate their impact on electrification planning across 22,696 population clusters. While all incentives encourage mini-grids and stand-alone systems, results show varied impacts, predominantly favouring mini-grids. Under the baseline, grid extension is optimal for 66% of clusters, followed by mini-grids (27%) and stand-alone systems (7%). Concessionary loans boost mini-grid and Stand-Alone Systems shares by 10% and 5%, respectively. Capital subsidies increase the mini-grid share to 41%, surpassing concessional loans (37%). Financing productive equipment enhances Stand-Alone Systems and mini-grid shares to 15% and 43%. Incentives impact LCOE, CAPEX, and OPEX, with average LCOE reducing to 0.31 EUR/kWh (concessionary loans), 0.30 EUR/kWh (capital subsidy), and 0.27 EUR/kWh (financing productive use). Financing productive uses proves decisively more effective in lowering costs for mini-grids and stand-alone systems than loans or capital subsidies. The important policy implications of this study reinforce the need for tailored incentives for distinct electrification options.

Duckweeds (Lemnaceae) rapidly produce clonal populations that make them ideal models in plant physiological and ecotoxicological research. Yet, despite their genetic homogeneity, duckweed colonies are clusters of successively produced fronds with different ontogenetic states, and this heterogeneity has rarely been studied. We analyzed frond-level photosynthetic responses of three duckweed species (Spirodela polyrhiza, Landoltia punctata and Lemna minor) to hexavalent chromium and nickel by means of chlorophyll fluorescence imaging. Our aim was to test whether fronds, or frond zones in their different developmental stages respond differently to heavy metal stress. Different response patterns were found for the three tested species. Young fronds of S. polyrhiza were more sensitive to chromate but less affected by nickel compared to mature ones, while in La. punctata the opposite was found. In Le. minor cultures, young fronds were more sensitive to both heavy metals compared to mature ones. Within-frond patterns indicated that chromate inhibited the marginal frond regions strongest. In La. punctata and Le. minor, nickel was most detrimental in the developing frond regions. In contrast, in S. polyrhiza the middle zone of both young and mature fronds was affected strongest by nickel. The observed patterns suggest that internal redistribution of toxicants plays a key role in shaping duckweed responses.Results highlight that ontogenetically different parts of duckweed plants respond differently to environmental stimuli. Since duckweed-based impact studies and economical applications rely strongly on the interactions between the duckweed colony and its environment, frond-, and within-frond level analysis of duckweed responses comprise a unique tool to reveal uptake, re-distribution and mode of action of environmentally relevant substances.

Integrins connect the extracellular matrix with the cell interior, and transduce signals through interactions of their cytoplasmic tails with cytoskeletal and signaling proteins. Using the yeast two-hybrid system, we isolated a novel splice variant (filamin-[B.sub.var-1]) of the filamentous actin cross-linking protein, filamin-B, that interacts with the cytoplasmic domain of the integrin [beta]1A and [beta]1D sub-units. RT-PCR analysis showed weak, but wide, expression of filamin-[B.sub.var-1] and a similar splice variant of filamin-A (filamin-[A.sub.var-1]) in human tissues. Furthermore, alternative splice variants of filamin-B and filamin-C, from which the flexible hinge-1 region is deleted ([DELTA]H1), were induced during in vitro differentiation of C2C12 mouse myoblasts. We show that both filamin-[A.sub.var-1] and filamin-[B.sub.var-1] bind more strongly than their wild-type isoforms to different integrin [beta] subunits. The mere presence of the high-affinity binding site for [beta]1A is not sufficient for targeting the filamin-[B.sub.var-1] construct to focal contacts. Interestingly, the simultaneous deletion of the H1 region is required for the localization of filamin-B at the tips of actin stress fibers. When expressed in C2C12 cells, filamin-[B.sub.var-1]([DELTA]H1) accelerates their differentiation into myotubes. Furthermore, filamin-B variants lacking the H1 region induce the formation of thinner myotubes than those in cells containing variants with this region. These findings suggest that specific combinations of filamin mRNA splicing events modulate the organization of the actin cytoskeleton and the binding affinity for integrins.

Abstract Due to a demonstrated lack of DNA repair deficiencies, clear cell renal cell carcinoma (ccRCC) has not benefitted from targeted synthetic lethality-based therapies. We investigated whether nucleotide excision repair (NER) deficiency is present in an identifiable subset of ccRCC cases that would render those tumors sensitive to therapy targeting this specific DNA repair pathway aberration. We used functional assays that detect UV-induced 6–4 pyrimidine-pyrimidone photoproducts to quantify NER deficiency in ccRCC cell lines. We also measured sensitivity to irofulven, an experimental cancer therapeutic agent that specifically targets cells with inactivated transcription-coupled nucleotide excision repair (TC-NER). In order to detect NER deficiency in clinical biopsies, we assessed whole exome sequencing data for the presence of an NER deficiency associated mutational signature previously identified in ERCC2 mutant bladder cancer. Functional assays showed NER deficiency in ccRCC cells. Some cell lines showed irofulven sensitivity at a concentration that is well tolerated by patients. Prostaglandin reductase 1 (PTGR1), which activates irofulven, was also associated with this sensitivity. Next generation sequencing data of the cell lines showed NER deficiency-associated mutational signatures. A significant subset of ccRCC patients had the same signature and high PTGR1 expression. ccRCC cell line-based analysis showed that NER deficiency is likely present in this cancer type. Approximately 10% of ccRCC patients in the TCGA cohort showed mutational signatures consistent with ERCC2 inactivation associated NER deficiency and also substantial levels of PTGR1 expression. These patients may be responsive to irofulven, a previously abandoned anticancer agent that has minimal activity in NER-proficient cells.

A study was conducted on cardiolipin-binding activity mediation by a light-chain sequence. The findings indicate that cardiolipin binding can be mediated by the VL sequence, in the absence of any other immunoglobulin domains. Moreover, this sequence is close to the germ-line configurations which may explain the incidence of these antibodies in different disorders associated with increased antibody production. The results also suggest that antigen specificity of certain antibodies may reside exclusively in the light-chain sequences.

In systemic sclerosis (SSc), fibrosis of the myocardium along with ongoing autoimmune inflammation can alter the electric function of the cardiac myocytes, which may increase the risk for ventricular arrhythmias and sudden cardiac death. We analyzed the electrocardiographic (ECG) variables describing ventricular repolarization such as QT interval, QT dispersion (QTd), T wave peak-to-end interval (Tpe), and arrhythmogeneity index (AIX) of 26 patients with SSc and 36 healthy controls. Furthermore, echocardiographic and laboratory parameters were examined, with a focus on inflammatory proteins like C-reactive ptotein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and progranulin (PGRN). The CRP, sICAM-1, and sVCAM-1 levels were positively correlated with the length of the QT interval. Although the serum PGRN levels were not increased in the SSc group compared to the controls, in SSc patients, the PGRN levels were positively correlated with the QT interval and the AIX. According to our results, we conclude that there may be a potential association between autoimmune inflammation and the risk for ventricular arrhythmias in patients with SSc. We emphasize that the measurement of laboratory parameters of inflammatory activity including CRP, PGRN, sVCAM-1, and sICAM-1 could be helpful in the prediction of sudden cardiac death in patients with SSc.

Kallistatin is an endogenous serine proteinase inhibitor with various functions, including antioxidative, anti-inflammatory, and anti-atherosclerotic properties. To date, associations between kallistatin and lipoprotein subfractions are poorly investigated. In this study, we enrolled 62 obese patients with type 2 diabetes (T2D), 106 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index, as well as 49 gender- and age-matched healthy, normal-weight controls. Serum kallistatin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint® (Quantimetrix Corp., Redondo Beach, CA, USA) gel electrophoresis. Kallistatin concentrations were significantly higher in T2D patients compared to NDO and control groups. We found significant positive correlations between very-low-density lipoprotein (VLDL), small high-density lipoprotein (HDL) subfractions, glucose, hemoglobin A1c (HbA1c), betatrophin, and kallistatin, while negative correlations were detected between mean low-density lipoprotein (LDL) size, large and intermediate HDL subfractions, and kallistatin in the whole study population. The best predictor of kallistatin was HbA1c in T2D patients, high-sensitivity C-reactive protein (hsCRP) and betatrophin in NDO patients, and hsCRP in controls. Our results indicate that kallistatin expression might be induced by persistent hyperglycemia in T2D, while in nondiabetic subjects, its production might be associated with systemic inflammation. The correlation of kallistatin with lipid subfractions may suggest its putative role in atherogenesis.

The availability of new-generation femtosecond lasers capable of delivering pulses with energies in the hundreds of mJ, or even in the joules range, has called for a revision of the effect of scaling spot size on the material distribution within the plasma plume. Employing a state-of-the-art Szatmári-type hybrid dye-excimer laser system emitting 248 nm pulses with a maximum energy of 20 mJ and duration of 600 fs, copper films were grown in the classical pulsed laser deposition geometry. The exceptionally clean temporal profile of the laser pulses yielded a femtosecond component of 4.18 ± 0.19 mJ, accompanied by a 0.22 ± 0.01 mJ ASE pedestal on the target surface. While varying the spot sizes, the plasma plume consistently exhibited an extremely forward-peaked distribution. Deposition rates, defined as peak thickness per number of pulses, ranged from 0.030 to 0.114 nm/pulse, with a gradual narrowing of the thickness distribution as the spot area increased from 0.085 to 1.01 mm2 while keeping the pulse energy constant. The material distribution on the silicon substrates was characterized using the f(Θ) = AcoskΘ + (1 − A)cospΘ formalism, revealing exponents characterizing the forward-peaked component of the thickness profile of the film material along the axes, ranging from k = 15 up to exceptionally high values exceeding 50, as the spot area increased. Consequently, spot size control and outstanding beam quality ensured that majority of the ablated material was confined to the central region of the plume, indicating the potential of PLD (pulsed laser deposition) for highly efficient localized deposition of exotic materials.

Abstract To date, single-nucleotide polymorphisms (SNPs) have been the most intensively investigated class of polymorphisms in genome wide associations studies (GWAS), however, other classes such as insertion-deletion or multiple nucleotide length polymorphism (MNLPs) may also confer disease risk. Multiple reports have shown that the 5p15.33 prostate cancer risk region is a particularly strong expression quantitative trait locus (eQTL) for Iroquois Homeobox 4 (IRX4) transcripts. Here, we demonstrate using epigenome and genome editing that a biallelic (21 and 47 base pairs (bp)) MNLP is the causal variant regulating IRX4 transcript levels. In LNCaP prostate cancer cells (homozygous for the 21 bp short allele), a single copy knock-in of the 47 bp long allele potently alters the chromatin state, enabling de novo functional binding of the androgen receptor (AR) associated with increased chromatin accessibility, Histone 3 lysine 27 acetylation (H3K27ac), and ~3-fold upregulation of IRX4 expression. We further show that an MNLP is amongst the strongest candidate susceptibility variants at two additional prostate cancer risk loci. We estimated that at least 5% of prostate cancer risk loci could be explained by functional non-SNP causal variants, which may have broader implications for other cancers GWAS. More generally, our results underscore the importance of investigating other classes of inherited variation as causal mediators of human traits.

Acetone-stabilized Au- and Sn-solvated metal atoms (SMAs) were used as to obtain Au- and AuSn-supported catalysts by simple impregnation on a reducible (TiO2) and a non-reducible (Al2O3) metal-oxide. Their catalytic behaviour was investigated for cyclohexane oxidation to cyclohexanol and cyclohexanone (KA oil), and their morphological and physical properties were studied by TEM, STEM-EDS and 119Sn-Mössbauer spectroscopy. The catalytic results firstly demonstrated that the bare supports played a role on the reaction mechanism, slowing down the formation of the oxidation products and directing the radical formation. Hereinafter, the comparison between the monometallic Au-supported catalysts and the corresponding bimetallic Au-Sn catalysts allowed for the understanding of the potential role of Sn. 119Sn-Mössbauer characterization analyses showed the presence of SnO2, which was recognized to favour the electrons’ exchange to form radicals, interacting with oxygen. Such interaction, in particular, could be favoured by the co-presence of Au. Moreover, the same metal composition on the catalyst surface resulted in a different catalytic behaviour depending on the support.

IntroductionAdult growth hormone deficiency (AGHD) is associated with a high prevalence of metabolic syndrome (MS), which contributes to the unfavorable cardiovascular risk profile in these patients. Insulin like growth factor-1 (IGF-1) is a widely used biomarker, however it does not always reflect the cardiometabolic risk and has a poor relationship with clinical efficacy endpoints. Consequently, there is an unmet need for biomarkers to monitor responses to GH-replacement. Afamin is a hormone-like glycoprotein, expressed in the liver. Higher afamin levels are strongly associated with MS and insulin resistance (IR). Although both MS and IR are very common in AGHD, afamin has not been investigated in these patients.PurposeTo investigate afamin as a potential biomarker in patients with AGHD.Materials and methodsParticipants included 20 AGHD patients (11 GH-substituted and 9 GH-unsubstituted) and 37 healthy controls. Subjects underwent routine laboratory examinations, anthropometric measurements, body composition analysis using multi-frequency bioelectrical impedance analysis (InBody720) and measurement of serum afamin concentrations. In GH-substituted subjects, GH-substitution was withdrawn for 2 months. Measurements were carried out right before GH-withdrawal, at the end of the 2-month withdrawal period, and 1 month after reinstituting GH-replacement therapy (GHRT).ResultsGH-unsubstituted patients demonstrated higher afamin levels compared to controls (p=0.03). Afamin positively correlated with skeletal muscle mass, bone mineral content, total body water, extracellular- and intracellular water content, insulin (all, p

EFOP-3.1.3-16-2016-00001, „Társadalmi felzárkózási és integrációs köznevelési intézkedések támogatása” címmel vettünk részt 2017 és 2020 között egy az Oktatási Hivatal által vezetett országos projektben, melyet egyszerűen „Esélyteremtő Óvoda” néven használtunk munkánk során. A projekt célja elsősorban az óvodák megsegítése volt a hátrányos helyzetű és halmozottan hátrányos helyzetű roma, cigány gyermekek nevelését, fejlesztését tekintve. A munka egy fontos szakasza volt az a felmérés, melyben egy sajátos – az óvodai élethez alkalmazkodó, az óvodapedagógusok megfigyeléseire épülő – képességfelmérést végeztünk el az intézmények aktív közreműködésével. Jelen tanulmányban a felmérés egy fontos aspektusát, a szociális kompetenciák vizsgálatát helyezzük előtérbe. Három kategóriában (énkép, társas kapcsolatok, érzelmi-akarati tulajdonságok), kategóriánként öt dimenzióban kaptunk eredményeket a három kiválasztott megye projektben részt vevő óvodáiból. A teljes felmérésben összesen 1112 gyermekről szolgáltattak információt az óvodák, melyből a három általunk elemzett megyét tekintve a következőképpen alakult a beérkezett válaszok száma: Borsod-Abaúj-Zemplén megyében 259, Hajdú-Bihar megyében 178, míg Szabolcs-Szatmár-Bereg megyében 271, azaz n=708 gyermekre vonatkozó óvodapedagógus állítás elemzésére került sor jelen tanulmányban. Az eredményekben szignifikáns különbség nem tapasztalható: mindössze néhány esetben tapasztaltunk Borsod-Abaúj-Zemplén megye kapcsán negatív irányú eltérést a szociális kompetenciák terén.

ABSTRACTBackground YouTube is one of the most widespread social media channels, which is of growing importance in science communication and health education. The validity of medical and health-related information available on YouTube cannot be assured, and videos often contain potentially misleading or inaccurate information. Communication on sport nutrition may have a profound effect on the change in nutrition behavior among athletes, so evidence-based nutrition information must reach athletes. The main goal of the research is to evaluate the quality, reliability, and applicability of sports nutrition YouTube videos as educational material for athletes.Methods A descriptive cross-sectional design was applied, and a systematic search was performed on YouTube. The quality and reliability of the videos were evaluated by applying the most frequently used and highly reliable scoring systems in the literature (e.g., DISCERN, Global Quality Score, and JAMA criteria) and a sports nutrition-specific scoring system (SNSS). Descriptive statistical analyses, two-sample t-test, Spearman correlation, Kruskal – Wallis, and Mann – Whitney U test were used to evaluate the results. A total of 114 YouTube videos met the inclusion criteria.Results In 25% of the videos, the sports nutrition information was presented by a dietitian, while in two-thirds, coaches and athletes and other professionals shared sports nutrition knowledge. In terms of video content, the three most common topics were nutrition and health (33%), special diets (21%), and the training diet (17%). For the majority of the videos that received low GQS, JAMAS, DISCERN, and SNSS scores, the accuracy and quality of the analyzed YouTube videos on sports nutrition were inadequate. Videos uploaded by dietitians achieved significantly higher DISCERN, JAMAS, GQS, and SNSS scores. The GQS, SNSS, and DISCERN scores of videos from sports organizations, nonprofit organizations, and independent user sources were lower compared to videos uploaded by academic and professional organizations. Popular sport nutrition videos among users that contain personal stories or the experiences of athletes were deemed less reliable by experts or showed lower educational quality. Henceforth, we found a negative correlation between video popularity and JAMAS, GQS, and SNSS scores.Conclusion This study revealed that sports nutrition videos on the YouTube video platform show low accuracy and reliability. Professionals working with athletes need to consider misconceptions from sports nutrition videos in their nutrition counseling practice. Due to the popularity of the videos, professionals and professional organizations could use YouTube as an online educational tool to increase the nutrition knowledge of athletes.

Short sprints are predominantly assessed using timing gates and analyzed through parameters of the mono-exponential equation, including estimated maximal sprinting speed (MSS) and relative acceleration (TAU), derived maximum acceleration (MAC), and relative propulsive maximal power (PMAX), further referred to as the No Correction model. However, the frequently recommended flying start technique introduces a bias during parameter estimation. To correct this, two additional models (Estimated TC and Estimated FD) were proposed. To estimate model precision and sensitivity to detect the change, 31 basketball players executed multiple 30 m sprints. Athlete performance was simultaneously measured by a laser gun and timing gates positioned at 5, 10, 20, and 30 m. Short sprint parameters were estimated using a laser gun, representing the criterion measure, and five different timing gate models, representing the practical measures. Only the MSS parameter demonstrated a high agreement between the laser gun and timing gate models, using the percent mean absolute difference (%MAD) estimator (%MAD < 10%). The MSS parameter also showed the highest sensitivity, using the minimum detectable change estimator (%MDC95), with an estimated %MDC95 < 17%. Interestingly, sensitivity was the highest for the No Correction model (%MDC95 < 7%). All other parameters and models demonstrated an unsatisfying level of sensitivity. Thus, sports practitioners should be cautious when using timing gates to estimate maximum acceleration indices and changes in their respective levels.