This study aims to determine the Blaťácké zlato cheese in vitro antioxidant activity and its correlation with specific peptides. A general physicochemical evaluation was also conducted, considering possible differences between batches. The antioxidant activity focused mainly on the nitrogen fractions with the shortest-chain peptides. Other parameters were evaluated, including color, weight, size, moisture, dry matter, and texture analysis, which included the whole cheese hardness and the texture profile analysis. The ethanol soluble (EtOH-SN) and non-protein nitrogen (NPN) fractions were selected to evaluate antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods, total phenol content (TPC), and peptide profiles. Our findings revealed significant differences between batches for NPN ABTS activity and EtOH-SN TPC. Significant differences were observed for water activity, moisture, dry matter, moisture on fat-free basis (MFFB), and pH in the central surface. DPPH and TPC showed a similar behavior, and NPN showed higher values than the EtOH-SN fraction. However, the opposite was observed for ABTS. Significant correlations were found for the biological activities with individual peaks of their corresponding HPLC peptide profiles. Finally, the principal component analysis separated the cheeses according to the batch, mainly due to specific peptides.

• Keywords
• ABTS, Blaťácké zlato cheese, DPPH, cheese characterization, color, total polyphenol content,
• Publication type
• Journal Article MeSH

Chalcones, potential anticancer agents, have shown promise in the suppression of multidrug resistance due to the inhibition of drug efflux driven by certain adenosine triphosphate (ATP)-binding cassette (ABC) transporters. The gene and protein expression of chosen ABC transporters (multidrug resistance protein 1, ABCB1; multidrug resistance-associated protein 1, ABCC1; and breast cancer resistance protein, ABCG2) in human colorectal cancer cells (COLO 205 and COLO 320, which overexpress active ABCB1) was mainly studied in this work under the influence of a novel synthetic acridine-based chalcone, 1C. While gene expression dropped just at 24 h, compound 1C selectively suppressed colorectal cancer cell growth and greatly lowered ABCB1 protein levels in COLO 320 cells at 24, 48, and 72 h. It also reduced ABCC1 protein levels after 48 h. Molecular docking and ATPase tests show that 1C probably acts as an allosteric modulator of ABCB1. It also lowered galectin-1 (GAL1) expression in COLO 205 cells at 24 h. Functional tests on COLO cells revealed ABCB1 and ABCC1/2 to be major contributors to multidrug resistance in both. Overall, 1C transiently lowered GAL1 in COLO 205 while affecting important functional ABC transporters, mostly ABCB1 and to a lesser extent ABCC1 in COLO 320 cells. COLO 320's absence of GAL1 expression points to a possible yet unknown interaction between GAL1 and ABCB1.

• Keywords
• ABCB1, ABCC1, ABCG2, chalcone, colorectal carcinoma, drug efflux, expression, galectin-1, multidrug resistance, transporter,
• MeSH
• ATP Binding Cassette Transporter, Subfamily G, Member 2 metabolism   MeSH
• ATP-Binding Cassette Transporters * metabolism   chemistry   genetics   MeSH
• Acridines * chemistry   pharmacology   MeSH
• Chalcone * pharmacology   chemistry   MeSH
• Chalcones * pharmacology   chemistry   MeSH
• Drug Resistance, Neoplasm drug effects   MeSH
• Colorectal Neoplasms metabolism   drug therapy   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• ATP Binding Cassette Transporter, Subfamily B metabolism   genetics   MeSH
• Cell Proliferation drug effects   MeSH
• Multidrug Resistance-Associated Protein 2 MeSH
• Multidrug Resistance-Associated Proteins metabolism   genetics   MeSH
• Antineoplastic Agents * pharmacology   chemistry   MeSH
• Gene Expression Regulation, Neoplastic drug effects   MeSH
• Molecular Docking Simulation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• ATP Binding Cassette Transporter, Subfamily G, Member 2 MeSH
• ATP-Binding Cassette Transporters * MeSH
• ABCB1 protein, human MeSH Browser
• ABCC2 protein, human MeSH Browser
• Acridines * MeSH
• Chalcone * MeSH
• Chalcones * MeSH
• multidrug resistance-associated protein 1 MeSH Browser
• ATP Binding Cassette Transporter, Subfamily B MeSH
• Multidrug Resistance-Associated Protein 2 MeSH
• Multidrug Resistance-Associated Proteins MeSH
• Antineoplastic Agents * MeSH

Approaches to DNA extraction play a crucial role in determining the variability of results obtained through 16S rRNA amplicon sequencing. Particularly, clay-rich samples can impede the efficiency of various standard cultivation-independent techniques. We conducted an inter-laboratory comparison study to thoroughly assess the efficacy of two published DNA extraction methods (kit-based and phenol-chloroform-based) specifically designed for bentonite samples. To this end, we spiked Wyoming MX 80 bentonite with two different mock communities and compared the obtained DNA yield and purity, the presence of contaminants and the community profile. Our findings suggest that both methods are equally viable, with the best choice depending on the specific requirements of the downstream analysis. However, it is crucial to maintain consistency in the chosen method, as comparing results becomes challenging, particularly in the presence of bentonite. In summary, our study emphasizes the significance of standardized DNA extraction methods and underscores the importance of validating these methods using appropriate controls when studying microbial communities with 16S rRNA amplicon sequencing, particularly in environments characterized by low biomass and clay-rich compositions. Additionally, slight modifications to one of the extraction methods can substantially enhance its efficiency.

• MeSH
• Bacteria genetics   classification   isolation & purification   MeSH
• Bentonite * chemistry   MeSH
• DNA, Bacterial * genetics   isolation & purification   MeSH
• Microbiota genetics   MeSH
• Soil Microbiology MeSH
• RNA, Ribosomal, 16S * genetics   MeSH
• Sequence Analysis, DNA MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Bentonite * MeSH
• DNA, Bacterial * MeSH
• RNA, Ribosomal, 16S * MeSH

Homologous recombination (HR) factors are crucial for DSB repair and processing stalled replication forks. RAD51 paralogs, including RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3, have emerged as essential tumour suppressors, forming two subcomplexes, BCDX2 and CX3. Mutations in these genes are associated with cancer susceptibility and Fanconi anaemia, yet their biochemical activities remain unclear. This study reveals a linear arrangement of BCDX2 subunits compared to the RAD51 ring. BCDX2 shows a strong affinity towards single-stranded DNA (ssDNA) via unique binding mechanism compared to RAD51, and a contribution of DX2 subunits in binding branched DNA substrates. We demonstrate that BCDX2 facilitates RAD51 loading on ssDNA by suppressing the cooperative requirement of RAD51 binding to DNA and stabilizing the filament. Notably, BCDX2 also promotes RAD51 loading on short ssDNA and reversed replication fork substrates. Moreover, while mutants defective in ssDNA binding retain the ability to bind branched DNA substrates, they still facilitate RAD51 loading onto reversed replication forks. Our study provides mechanistic insights into how the BCDX2 complex stimulates the formation of BRCA2-independent RAD51 filaments on short stretches of ssDNA present at ssDNA gaps or stalled replication forks, highlighting its role in genome maintenance and DNA repair.

• MeSH
• DNA-Binding Proteins * metabolism   genetics   MeSH
• DNA, Single-Stranded * metabolism   genetics   MeSH
• Humans MeSH
• Multiprotein Complexes MeSH
• Mutation MeSH
• Rad51 Recombinase * metabolism   genetics   MeSH
• DNA Replication * genetics   MeSH
• Protein Binding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• DNA-Binding Proteins * MeSH
• DNA, Single-Stranded * MeSH
• Multiprotein Complexes MeSH
• RAD51 protein, human MeSH Browser
• Rad51 Recombinase * MeSH

Systems biology aims to understand living organisms through mathematically modeling their behaviors at different organizational levels, ranging from molecules to populations. Modeling involves several steps, from determining the model purpose to developing the mathematical model, implementing it computationally, simulating the model's behavior, evaluating, and refining the model. Importantly, model simulation results must be reproducible, ensuring that other researchers can obtain the same results after writing the code de novo and/or using different software tools. Guidelines to increase model reproducibility have been published. However, reproducibility remains a major challenge in this field. In this paper, we tackle this challenge for physiologically-based pharmacokinetic (PBPK) models, which represent the pharmacokinetics of chemicals following exposure in humans or animals. We summarize recommendations for PBPK model reporting that should apply during model development and implementation, in order to ensure model reproducibility and comprehensibility. We make a proposal aiming to harmonize abbreviations used in PBPK models. To illustrate these recommendations, we present an original and reproducible PBPK model code in MATLAB, alongside an example of MATLAB code converted to Systems Biology Markup Language format using MOCCASIN. As directions for future improvement, more tools to convert computational PBPK models from different software platforms into standard formats would increase the interoperability of these models. The application of other systems biology standards to PBPK models is encouraged. This work is the result of an interdisciplinary collaboration involving the ELIXIR systems biology community. More interdisciplinary collaborations like this would facilitate further harmonization and application of good modeling practices in different systems biology fields.

• Keywords
• MATLAB, SBML, model code, pharmacokinetics, reproducibility, systems biology,
• MeSH
• Models, Biological * MeSH
• Pharmacokinetics * MeSH
• Humans MeSH
• Computer Simulation MeSH
• Reproducibility of Results MeSH
• Software * MeSH
• Systems Biology * methods   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Altermagnetic (AM) materials exhibit non-relativistic, momentum-dependent spin-split states, ushering in new opportunities for spin electronic devices. While the characteristics of spin-splitting are documented within the framework of the non-relativistic spin group symmetry, there is limited exploration of the inclusion of relativistic symmetry and its impact on the emergence of a novel spin-splitting in the band structure. This study delves into the intricate relativistic electronic structure of an AM material, α-MnTe. Employing temperature-dependent angle-resolved photoelectron spectroscopy across the AM phase transition, the emergence of a relativistic valence band splitting concurrent with the establishment of magnetic order is elucidated. This discovery is validated through disordered local moment calculations, modeling the influence of magnetic order on the electronic structure and confirming the magnetic origin of the observed splitting. The temperature-dependent splitting is ascribed to the advent of relativistic spin-splitting resulting from the strengthening of AM order in α-MnTe as the temperature decreases. This sheds light on a previously unexplored facet of this intriguing material.

• Keywords
• altermagnetism, angle‐resolved photoemission spectroscopy, electronic band structure, spintronics,
• Publication type
• Journal Article MeSH

Introgression allows polyploid species to acquire new genomic content from diploid progenitors or from other unrelated diploid or polyploid lineages, contributing to genetic diversity and facilitating adaptive allele discovery. In some cases, high levels of introgression elicit the replacement of large numbers of alleles inherited from the polyploid's ancestral species, profoundly reshaping the polyploid's genomic composition. In such complex polyploids, it is often difficult to determine which taxa were the progenitor species and which taxa provided additional introgressive blocks through subsequent hybridization. Here, we use population-level genomic data to reconstruct the phylogenetic history of Betula pubescens (downy birch), a tetraploid species often assumed to be of allopolyploid origin and which is known to hybridize with at least four other birch species. This was achieved by modeling polyploidization and introgression events under the multispecies coalescent and then using an approximate Bayesian computation rejection algorithm to evaluate and compare competing polyploidization models. We provide evidence that B. pubescens is the outcome of an autoploid genome doubling event in the common ancestor of B. pendula and its extant sister species, B. platyphylla, that took place approximately 178,000-188,000 generations ago. Extensive hybridization with B. pendula, B. nana, and B. humilis followed in the aftermath of autopolyploidization, with the relative contribution of each of these species to the B. pubescens genome varying markedly across the species' range. Functional analysis of B. pubescens loci containing alleles introgressed from B. nana identified multiple genes involved in climate adaptation, while loci containing alleles derived from B. humilis revealed several genes involved in the regulation of meiotic stability and pollen viability in plant species.

• Keywords
• Allopolyploidy, Betula, autopolyploidy, gene flow, genomic polarization, homoeologs, interploidal, introgressive hybridization, polyploid phylogenetics, polyploidization simulation, reticulate evolution,
• MeSH
• Alleles * MeSH
• Betula * genetics   classification   MeSH
• Phylogeny * MeSH
• Genome, Plant * MeSH
• Genetic Introgression MeSH
• Hybridization, Genetic MeSH
• Polyploidy * MeSH
• Publication type
• Journal Article MeSH

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.

• Keywords
• COVID-19, Europe, SARS-CoV-2, barriers, pandemic preparedness, vaccinations, vaccine education, vaccine trials,
• Publication type
• Journal Article MeSH

Recent RNA sequencing studies have given us a deeper insight into the cariogenic impact of carbohydrate sources in the bacterium Streptococcus mutans, the principal microbial agent in dental caries etiopathogenesis. The process of dental caries development is facilitated by the ability of this bacterium to ferment some carbohydrates into organic acids contributing to a pH decrease in the oral cavity and the demineralization of the hard tissues of the tooth. Furthermore, in dental caries progression, biofilm formation, which starts and ends with free planktonic cells, plays an important role and has several unique properties called virulence factors. The most cariogenic carbohydrate is sucrose, an easily metabolizable source of energy that induces the acidification and synthesis of glucans, forming typical bacterial cell clumps. We used multifaceted methodological approaches to compare the transcriptomic and metabolomic profiles of S. mutans growing in planktonic culture on preferred and nonpreferred carbohydrates and in fasting conditions. Streptococcus mutans in a planktonic culture with lactose produced the same pH drop as glucose and sucrose. By contrast, xylitol and lactose showed high effectiveness in regulating intracellular polysaccharide metabolism, cell wall structure, and overall virulence involved in the initial phase of biofilm formation and structure but with an opposite pattern compared with sucrose and glucose. Our results confirmed the recent findings that xylitol and lactose play a vital role in biofilm structure. However, they do not reduce its formation, which is related to the creation of a cariogenic environment.

• Keywords
• RNA-Seq, Streptococcus mutans, cariogenic carbohydrates, cell wall, metabolome, transcriptome,
• Publication type
• Journal Article MeSH

Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel-like scaffolds and endothelial cells seeded in their lumen form native-like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites the bioprinted vasculature and endothelium to cooperatively create vessels, enabling tissue perfusion through the scaffold lumen. Using a cuffing microsurgery approach, the engineered tissue is directly anastomosed with a rat femoral artery, promoting a rich host vasculature within the implanted tissue. After two weeks in vivo, contrast microcomputer tomography imaging and lectin perfusion of explanted engineered tissues verify the host ingrowth vasculature's functionality. Furthermore, the hierarchical vessel network (VesselNet) supports in vitro functionality of cardiomyocytes. Finally, the proposed approach is expanded to mimic complex structures with native-like millimetric vessels. This work presents a novel strategy aiming to create fully-engineered patient-specific thick tissue flaps.

• Keywords
• 3D bioprinting, ECM bioink, engineered flap, personalized medicine, tissue engineering, vascularization,
• MeSH
• Printing, Three-Dimensional MeSH
• Femoral Artery surgery   MeSH
• Biomimetic Materials chemistry   MeSH
• Bioprinting methods   MeSH
• Endothelial Cells cytology   metabolism   MeSH
• Hydrogels chemistry   MeSH
• Ink MeSH
• Stem Cells cytology   metabolism   MeSH
• Collagen Type I chemistry   genetics   metabolism   MeSH
• Rats MeSH
• Humans MeSH
• Methacrylates chemistry   MeSH
• Polymers chemistry   MeSH
• Rats, Sprague-Dawley MeSH
• Prostheses and Implants MeSH
• Tissue Engineering * MeSH
• Tissue Scaffolds chemistry   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Hydrogels MeSH
• Collagen Type I MeSH
• Methacrylates MeSH
• Polymers MeSH