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Mycena s.s. is a ubiquitous mushroom genus whose members degrade multiple dead plant substrates and opportunistically invade living plant roots. Having sequenced the nuclear genomes of 24 Mycena species, we find them to defy the expected patterns for fungi based on both their traditionally perceived saprotrophic ecology and substrate specializations. Mycena displayed massive genome expansions overall affecting all gene families, driven by novel gene family emergence, gene duplications, enlarged secretomes encoding polysaccharide degradation enzymes, transposable element (TE) proliferation, and horizontal gene transfers. Mainly due to TE proliferation, Arctic Mycena species display genomes of up to 502 Mbp (2-8× the temperate Mycena), the largest among mushroom-forming Agaricomycetes, indicating a possible evolutionary convergence to genomic expansions sometimes seen in Arctic plants. Overall, Mycena show highly unusual, varied mosaic-like genomic structures adaptable to multiple lifestyles, providing genomic illustration for the growing realization that fungal niche adaptations can be far more fluid than traditionally believed.

Contamination of genomes is an increasingly recognized problem affecting several downstream applications, from comparative evolutionary genomics to metagenomics. Here we introduce ContScout, a precise tool for eliminating foreign sequences from annotated genomes. It achieves high specificity and sensitivity on synthetic benchmark data even when the contaminant is a closely related species, outperforms competing tools, and can distinguish horizontal gene transfer from contamination. A screen of 844 eukaryotic genomes for contamination identified bacteria as the most common source, followed by fungi and plants. Furthermore, we show that contaminants in ancestral genome reconstructions lead to erroneous early origins of genes and inflate gene loss rates, leading to a false notion of complex ancestral genomes. Taken together, we offer here a tool for sensitive removal of foreign proteins, identify and remove contaminants from diverse eukaryotic genomes and evaluate their impact on phylogenomic analyses.

Currently, there is no widely accepted criterion for judging the efficacy of CRT treatment. Patients underwent CRT implantation have most often been classified as either responders or non-responders based on the occurrence or absence of reverse remodelling following CRT. Based on this definition, nearly one-third of patients are considered as non-responders with a less favourable prognosis compared to responders. Recent recommendations have revised the previous terminologies. Accordingly, the CRT non-responder definition have-been re-defined as those who deteriorate (progressors) and remain stable for years (non-progressor) after CRT implantation. Considering the progressive nature of HF, non-progression could still represent a response to the device therapy and thereby classifying these patients as non-responders might be misleading. The background of the suboptimal CRT response is multifactorial, requiring a multidisciplinary approach for improving the effectiveness of CRT treatment. Therefore, we care must be taken on the appropriate patient selection and optimisation of the medications prior to implantation, currently available technical options and innovations during the intervention, device optimisation post-implantation, as well as on the management of comorbidities.

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]

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]

Juveniles of three cyprinids with various diets and habitat preferences were collected from the Szamos River (Hungary) during a period of pollution in November 2013: the herbivorous, benthic nase (Chondrostoma nasus), the benthivorous, benthic barbel (Barbus barbus), and the omnivorous, pelagic chub (Squalius cephalus). Our study aimed to assess the accumulation of these elements across species with varying diets and habitat preferences, as well as their potential role in biomonitoring efforts. The Ca, K, Mg, Na, Cd, Cr, Cu, Fe, Mn, Pb, Sr, and Zn concentration was analyzed in muscle, gills, and liver using MP-AES. The muscle and gill concentrations of Cr, Cu, Fe, and Zn increased with trophic level. At the same time, several differences were found among the trace element patterns related to habitat preferences. The trace elements, including Cd, Pb, and Zn, which exceeded threshold concentrations in the water, exhibited higher accumulations mainly in the muscle and gills of the pelagic chub. Furthermore, the elevated concentrations of trace elements in sediments (Cr, Cu, Mn) demonstrated higher accumulation in the benthic nase and barbel. Our findings show habitat preference as a key factor in juvenile bioindicator capability, advocating for the simultaneous use of pelagic and benthic juveniles to assess water and sediment pollution status. [ABSTRACT FROM AUTHOR]

The uptake of complex technologies and platforms has resulted in several challenges in the pricing and reimbursement of innovative pharmaceuticals. To address these challenges, plenty of concepts have already been described in the scientific literature about innovative value judgment or payment models, which are either (1) remaining theoretical; or (2) applied only in pilots with limited impact on patient access; or (3) applied so heterogeneously in many different countries that it prevents the health care industry from meeting expectations of HTA bodies and health care payers in the evidence requirements or offerings in different jurisdictions. This paper provides perspectives on how to reduce the heterogeneity of pharmaceutical payment models across European countries in five areas, including 1) extended evaluation frameworks, 2) performance-based risk-sharing agreements, 3) pooled procurement for low volume or urgent technologies, 4) alternative access schemes, and 5) delayed payment models for technologies with high upfront costs. Whilst pricing and reimbursement decisions will remain a competence of EU member states, there is a need for alignment of European pharmaceutical payment model components in critical areas with the ultimate objective of improving the equitable access of European patients to increasingly complex pharmaceutical technologies. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy is a highly-conserved catabolic procss eliminating dysfunctional cellular components and invading pathogens. Autophagy malfunction contributes to disorders such as cancer, neurodegenerative and inflammatory diseases. Understanding autophagy regulation in health and disease has been the focus of the last decades. We previously provided an integrated database for autophagy research, the Autophagy Regulatory Network (ARN). For the last eight years, this resource has been used by thousands of users. Here, we present a new and upgraded resource, AutophagyNet. It builds on the previous database but contains major improvements to address user feedback and novel needs due to the advancement in omics data availability. AutophagyNet contains updated interaction curation and integration of over 280,000 experimentally verified interactions between core autophagy proteins and their protein, transcriptional and post-transcriptional regulators as well as their potential upstream pathway connections. AutophagyNet provides annotations for each core protein about their role: 1) in different types of autophagy (mitophagy, xenophagy, etc.); 2) in distinct stages of autophagy (initiation, expansion, termination, etc.); 3) with subcellular and tissue-specific localization. These annotations can be used to filter the dataset, providing customizable download options tailored to the user's needs. The resource is available in various file formats (e.g. CSV, BioPAX and PSI-MI), and data can be analyzed and visualized directly in Cytoscape. The multi-layered regulation of autophagy can be analyzed by combining AutophagyNet with tissue- or cell type-specific (multi-)omics datasets (e.g. transcriptomic or proteomic data). The resource is publicly accessible at . Abbreviations: ARN: Autophagy Regulatory Network; ATG: autophagy related; BCR: B cell receptor pathway; BECN1: beclin 1; GABARAP: GABA type A receptor-associated protein; IIP: innate immune pathway; LIR: LC3-interacting region; lncRNA: long non-coding RNA; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; miRNA: microRNA; NHR: nuclear hormone receptor; PTM: post-translational modification; RTK: receptor tyrosine kinase; TCR: T cell receptor; TLR: toll like receptor. [ABSTRACT FROM AUTHOR]

Plastic, integral to food packaging since the 1950s, has become a global environmental concern due to its contribution to microplastic pollution. Microplastics harm ecosystems, impacting wildlife and human health. Amid increasing focus on sustainability, global initiatives target sustainable production and consumption, but consumers struggle to verify product claims, leading to potential greenwashing, particularly in the food industry. We conducted an experiment focusing on pasta products with varied packaging and labeling attributes. Findings suggest that consumers are willing to pay more for products with both biodegradable packaging and Product Environmental Footprint (PEF) labels, indicating heightened trust and perceived sustainability. Information about microplastics' adverse environmental effects influenced consumer valuation, particularly among females, higher-income individuals, and those with stronger environmental concerns., (© 2024. The Author(s).)