Miracle-dz/UniFAR-FTUs huggingface dataset:
Hierarchic regulation of a metabolic pathway: H-NS, CRP, and SsrB control myo-inositol utilization by Salmonella enterica

ABSTRACT The metabolic island GEI4417/4436 of Salmonella enterica serovar Typhimurium (S. Typhimurium) enables the degradation of myo-inositol (MI) as the sole carbon and energy source. The island encodes two regulatory factors, the autoregulated repressor IolR that inhibits the transcription of most iol genes in the absence of MI, and the activator ReiD that induces the expression of an iol gene operon that is not controlled by IolR. In this study, we investigated the putative role of global regulators in the control of MI utilization by S. Typhimurium. The histone-like nucleoid structuring protein H-NS is demonstrated here to interact with 16 regions of GEI4417/4436 and to silence the transcriptional activity of the promoters P reiD and P iolE , thus controlling the expression of genes initial for MI degradation. The cAMP-binding regulatory protein (CRP) is shown to bind numerous promoters in GEI4417/4436 and is required for the growth of S. Typhimurium strain 14028 in a minimal medium with MI. The binding kinetics of H-NS and CRP toward promoters of GEI4417/4436 were quantified by surface resonance spectroscopy, showing that H-NS weakly binds to promoters of initial genes and that CRP has a high affinity to promoters of all genes essential for MI utilization. Furthermore, three promoters of the metabolic island were identified here to belong to the virulon of the two-component system SsrA/SsrB of salmonellae as demonstrated by electrophoretic mobility shift assays and the use of chromosomal luciferase reporter fusions. IMPORTANCE The capacity to utilize myo-inositol (MI) as sole carbon and energy source is widespread among bacteria, among them the intestinal pathogen S. Typhimurium. This study elucidates the complex and hierarchical regulation that underlies the utilization of MI by S. Typhimurium under substrate limitation. A total of seven regulatory factors have been identified so far, allowing the pathogen an environment-dependent, efficient, and fine-tuned regulation of a metabolic property that provides growth advantages in different environments. The capacity to utilize myo-inositol (MI) as sole carbon and energy source is widespread among bacteria, among them the intestinal pathogen S. Typhimurium. This study elucidates the complex and hierarchical regulation that underlies the utilization of MI by S. Typhimurium under substrate limitation. A total of seven regulatory factors have been identified so far, allowing the pathogen an environment-dependent, efficient, and fine-tuned regulation of a metabolic property that provides growth advantages in different environments.
Improved fast Fourier solution based on transport of intensity equation

The phase recovery algorithm based on the transport of intensity equation uses the fast Fourier solution to calculate the phase from the acquired intensity, but the solution accuracy is not high, and there will be instability caused by zero points and minimum points. Aiming at this problem, An improved fast Fourier solution based on the intensity transfer equation is proposed. By finding a suitable constant value to replace the focused intensity value in the traditional formula, the initial guess solution of the phase is solved; the initial phase and the focused intensity form a new complex amplitude, and then a new intensity differential is obtained in the form of angular spectrum propagation, and then the new The intensity differential of is substituted into the phase solution formula to obtain a new phase, so as to iteratively optimize the phase; when the iteration converges, the exact solution of the phase can be obtained. This solution can bypass the instability caused by the zero point and the minimum value point and has the advantage of high precision. Keywords: Transport of intensity equation, Intensity differential, Iterative optimization, Angular spectrum propagation, Fast Fourier solution, phase recovery.
Mucosal washes are useful for sampling intestinal mucus-associated microbiota despite low biomass

Exploring the dynamic relationship between mucus-associated microbiota and host health is pivotal, yet prevalent studies using stool samples may not accurately represent these bacteria. Here, we explored mucus-associated microbiota in the gastrointestinal tract of mice and the terminal ileum in humans, using three different sample types: mucosal washes, scraping, and intestinal content in mice and biopsies and mucosal washes in humans. We employed DNA quantification and 16S rRNA sequencing to assess how comparable the information yielded from different sample types, evaluating findings relative to expectations from state-of-the-art and under controlled benchmarks. Mucosal washes in mice exhibited higher bacterial DNA and lower host DNA contamination than scraping samples. Similarly, in humans, washes surpassed biopsies in bacterial yield. Despite variations in read counts, microbiota diversity and composition remained remarkably similar between methods in both species, faithfully reflecting expected genotypic and phenotypic differences. We conclude that washes reduce host contamination without inducing substantial compositional bias when sampling mucosal microbiota. Our findings emphasize mucosal washes as alternatives to biopsies in humans and scrapings in mice, providing insights for improving result transferability across hosts. Our research underscores the importance of considering the mucus-associated microbiota to track host-microbiome interactions closer to their actual interface surface.
Determining the affinities of high-affinity antibodies using KinExA and surface plasmon resonance

ABSTRACT Accurate and efficient affinity measurement techniques are essential for the biophysical characterization of therapeutic monoclonal antibodies, one of the fastest growing drug classes. Surface plasmon resonance (SPR) is widely used for determining antibody affinity, but does not perform well with extremely high affinity (low picomolar to femtomolar range) molecules. In this study, we compare the SPR-based Carterra LSA and the kinetic exclusion assay (KinExA) for measuring the affinities of 48 antibodies generated against the SARS-CoV-2 receptor-binding domain. These data reveal that high-affinity antibodies can be generated straight from selections using high-quality in vitro library platforms with 54% correspondence between affinities measured using LSA and KinExA. Generally, where there was a 2-fold or greater difference between LSA and KinExA, KinExA reported that affinities were tighter. We highlight the differences between LSA and KinExA, identifying the benefits and pitfalls of each in terms of dynamic range and throughput. Furthermore, we demonstrate for the first time that single-point screening with KinExA can significantly improve throughput while maintaining a strong correlation with full binding curve equilibrium measurements, enabling the accurate rank-ordering of clones with exceptionally tight binding properties.
Pharmacological characterization of seven human histamine H3 receptor isoforms

The histamine H3 receptor (H3R) regulates as a presynaptic G protein-coupled receptor the release of histamine and other neurotransmitters in the brain, and is consequently a potential therapeutic target for neuronal disorders. The human H3R encodes for seven splice variants that vary in the length of intracellular loop 3 and/or the C-terminal tail but are all able to induce heterotrimeric Gi protein signaling. The last two decades H3R drug discovery and lead optimization has been exclusively focused on the 445 amino acids-long reference isoform H3R-445. In this study, we pharmacologically characterized for the first time all seven H3R isoforms by determining their binding affinities for reference histamine H3 receptor agonists and inverse agonists. The H3R-453, H3R-415, and H3R-413 isoforms display similar binding affinities for all ligands as the H3R-445. However, increased agonist binding affinities were observed for the three shorter isoforms H3R-329, H3R-365, and H3R-373, whereas inverse agonists such as the approved anti-narcolepsy drug pitolisant (Wakix®) displayed significantly decreased binding affinities for the latter two isoforms. This opposite change in binding affinity of agonist versus inverse agonists on H3R-365 and H3R-373 is associated with their higher constitutive activity in a cAMP biosensor assay as compared to the other 5 isoforms. The observed differences in pharmacology between longer and shorter H3R isoforms should be considered in future drug discovery programs.
comradesOO: An Object-Oriented R Package for the Analysis of RNA Structural Data Generated by RNA crosslinking experiments

Summary RNA (Ribonucleic Acid) molecules have secondary and tertiary structures in vivo which play a crucial role in cellular processes such as the regulation of gene expression, RNA processing, and localization. The ability to investigate these structures will enhance our understanding of their function and contribute to the diagnosis and treatment of diseases caused by RNA dysregulation. However, there are no mature pipelines or packages for processing and analysing complex in vivo RNA structural data. Here, we present COMRADES Object-Oriented (comradesOO), a novel software package for the comprehensive analysis of data derived from the COMRADES (Crosslinking of Matched RNA and Deep Sequencing) method. comradesOO offers a comprehensive pipeline from raw sequencing reads to the identification of RNA structural features. It includes read processing and alignment, clustering of duplexes, data exploration, folding and comparisons of RNA structures. comradesOO also enables comparisons between conditions, the identification of inter-RNA interactions, and the incorporation of reactivity data to improve structure prediction. Availability and Implementation comradesOO is freely available to non-commercial users and implemented in R, with the source code and documentation accessible at [https://CRAN.R-project.org/package=comradesOO]. The software is supported on Linux, macOS, and Windows platforms. Contact jlp76@cam.ac. uk Supplementary information Supplementary data are available at Bioinformatics online.
Interrelation between gut microbiota, SCFA, and fatty acid composition in pigs

ABSTRACT The gut microbiota is a key player in the host metabolism. Some bacteria are able to ferment non-digestible compounds and produce short-chain fatty acids that the host can later transform and accumulate in tissue. In this study, we aimed to better understand the relationships between the microorganisms and the short-chain fatty acid composition of the rectal content, including the possible linkage with the fatty acid composition in backfat and muscle of the pig. We studied a Duroc × Iberian crossbred population, and we found significant correlations between different bacterial and archaeal genera and the fatty acid profile. The abundance of n-butyric acid in the rectal content was positively associated with Prevotella spp. and negatively associated with Akkermansia spp. , while conversely, the abundance of acetic acid was negatively and positively associated with the levels of Prevotella spp. and Akkermansia spp. , respectively. The most abundant genus, Rikenellaceae RC9 gut group, had a positive correlation with palmitic acid in muscle and negative correlations with stearic acid in backfat and oleic acid in muscle. These results suggest the possible role of Prevotella spp. and Akkermansia spp. as biomarkers for acetic and n-butyric acids, and the relationship of Rikenellaceae RC9 gut group with the lipid metabolism, building up the potential, although indirect, role of the microbiota in the modification of the backfat and muscle fatty acid composition of the host. IMPORTANCE The vital role of the gut microbiota on its host metabolism makes it essential to know how its modulation is mirrored on the fatty acid composition of the host. Our findings suggest Prevotella spp. and Akkermansia spp. as potential biomarkers for the levels of beneficial short-chain fatty acids and the possible influence of Rikenellaceae RC9 gut group in the backfat and muscle fatty acid composition of the pig. The vital role of the gut microbiota on its host metabolism makes it essential to know how its modulation is mirrored on the fatty acid composition of the host. Our findings suggest Prevotella spp. and Akkermansia spp. as potential biomarkers for the levels of beneficial short-chain fatty acids and the possible influence of Rikenellaceae RC9 gut group in the backfat and muscle fatty acid composition of the pig.
A. castellanii and P. aeruginosa mutually exacerbate damage to corneal cells during coinfection

ABSTRACT Microorganisms that are involved in microbial invasion keratitis infiltrate the cornea and cause eye pain. Despite the administration of antimicrobial treatment, patients with amoebic keratitis develop bacterial coinfections. Pseudomonas aeruginosa infection accounts for 50% of the reported bacterial coinfections in these patients. However, the role of pathogenic bacteria in amoeba-induced corneal damage remains unclear. In our current study, we conducted assays to examine cytopathic effects and observed increased corneal cell damage in the group with secondary P. aeruginosa infections. Imaging revealed that the presence of A. castellanii enhanced the accumulation of P. aeruginosa in areas of cell monolayer leakage. We demonstrated that treatment of P. aeruginosa with amoeba-soluble antigen resulted in higher adhesion ability, increased biofilm formation, and more severe corneal cell damage. Overall, this research significantly contributes to our understanding of the risk of P. aeruginosa coinfection in the progression of Acanthamoeba keratitis. IMPORTANCE At the National Cheng Kung University Hospital, numerous cases of amoebic keratitis had been identified with concurrent bacterial infections. Among these bacterial coinfections, Pseudomonas aeruginosa accounted for 50% of the reported cases. However, the impact of pathogenic bacteria on amoeba-induced corneal damage remains unclear. In our study, we successfully demonstrated that P. aeruginosa accumulated on the Acanthamoeba castellanii surface and caused more severe corneal damage. We also indicated that the exposure of P. aeruginosa to amoeba-soluble antigens enhanced its adhesion ability, promoted biofilm formation, and led to more severe corneal cell damage. These findings significantly contributed to our understanding of the risk associated with P. aeruginosa coinfection in the progression of amoeba keratitis. At the National Cheng Kung University Hospital, numerous cases of amoebic keratitis had been identified with concurrent bacterial infections. Among these bacterial coinfections, Pseudomonas aeruginosa accounted for 50% of the reported cases. However, the impact of pathogenic bacteria on amoeba-induced corneal damage remains unclear. In our study, we successfully demonstrated that P. aeruginosa accumulated on the Acanthamoeba castellanii surface and caused more severe corneal damage. We also indicated that the exposure of P. aeruginosa to amoeba-soluble antigens enhanced its adhesion ability, promoted biofilm formation, and led to more severe corneal cell damage. These findings significantly contributed to our understanding of the risk associated with P. aeruginosa coinfection in the progression of amoeba keratitis.
The Time Secret of Chinese A-Share Systematic Risk: Overnight and Intraday

ABSTRACT Based on all daily A-share data from January 2006 to December 2021, this study examines the relationship between overnight and intraday returns and market beta using Fama-Macbeth regressions and panel regressions to explore the reasons for the weak correlation between systematic risk and full-day returns in the Chinese A-share market. The results show that the overnight risk premium of the Chinese A-share market is significantly negative. The intraday risk premium is negligible when portfolios are sorted by beta, industry and Book-to-Market ratios, and stock characteristics. The slope of the securities market line (SML) tends to zero due to the interaction of the uncertain intraday risk premium and the negative correlation between overnight returns and market risk.
Optimizing representations for integrative structural modeling using Bayesian model selection

Motivation Integrative structural modeling combines data from experiments, physical principles, statistics of previous structures, and prior models to obtain structures of macromolecular assemblies that are challenging to characterize experimentally. The choice of model representation is a key decision in integrative modeling, as it dictates the accuracy of scoring, efficiency of sampling, and resolution of analysis. But currently, the choice is usually made ad hoc, manually. Results Here, we report NestOR (Nested Sampling for Optimizing Representation), a fully automated, statistically rigorous method based on Bayesian model selection to identify the optimal coarse-grained representation for a given integrative modeling setup. Given an integrative modeling setup, it determines the optimal representations from given candidate representations based on their model evidence and sampling efficiency. The performance of NestOR was evaluated on a benchmark of four macromolecular assemblies. Availability NestOR is implemented in the Integrative Modeling Platform (https://integrativemodeling.org) and is available at https://github.com/isblab/nestor. Data for the benchmark is at https://www.doi. org/10.5281/zenodo.10360718. Supplementary Information is available online.
Teotil - Model for calculation of source dependent loads in river basins

The Teotil software is a model maker tool specialized for calculations of loads in sub-catchments with known interior drainage. The model consists of a package of pre-defined functions that the user may apply to make his own model for transport of a selected constituent in a specified drainage basin or basins. The first part of the report contents tips for a setup of the model and information about its possibilities. The second part is a manual in Teotil programming. 4 keywords, Norwegian 4 keywords, English 1. Teotil 1. Teotil 2. Forurensningsregnskap 2. Pollution budget 3. Nedbørfelt 3. Drainage basin 4. Veiledning 4. Manual Torulv Tjomsland John Rune Selvik Bjørn Faafeng Project manager Research manager Senior adviser ISBN 978-82-577-5649-9
Mobility patterns, transport and accessibility in peripheral settlements of Dar es Salaam

This paper is concerned with access to the city for urban residents living in the periphery of Dar es Salaam, Tanzania. The paper presents an analysis of the mobility practices of residents and investigates the mobility constraints they experience in relation to the limited accessibility provided by the urban transport system. The paper draws upon qualitative interviews with residents in the periphery as well as recently collected travel speed data and offers a unique combination of testimony with GIS-based modelling of overall accessibility. A central finding is the overall importance of regular mobility and access to the city for residents in the periphery. Regular mobility is an ingrained part of residents’ livelihood strategies. The majority of households rely on one or more members regularly travelling to central parts of the city in relation to their livelihood activities. The analysis reveals a widespread, near-to-universal, dependence on motorized transportation, with the vast majority depending on public transport. Raster-based modelling of overall accessibility provides an indication of the very high travel times endured by residents in the periphery. The analysis identifies and distinguishes between three overall mode types: 1) Private car, 2) public transport and 3) motorcycle/car combined with public transport. While private cars appear marginally faster, differences in travel times are actually limited. This suggests that travel times are less influenced by mode of transport than by road and traffic conditions and highlights how accessibility problems of peripheral settlements are not easily understood separately from the general dysfunctions of the overall mobility system of city.
Exploring the Influence of VDR Genetic Variants TaqI, ApaI, and FokI on COVID-19 Severity and Long-COVID-19 Symptoms

There is increasing evidence regarding the importance of vitamin D in the prognosis of coronavirus disease 2019 (COVID-19). Genetic variants in the vitamin D receptor (VDR) gene affect the response to vitamin D and have been linked to various diseases. This study investigated the associations of the major VDR genetic variants ApaI, FokI, and TaqI with the severity and long post-infection symptoms of COVID-19. In total, 100 Jordanian patients with confirmed COVID-19 were genotyped for the VDR ApaI, FokI, and TaqI variants using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. COVID-19 severity, the most commonly reported long-COVID-19 symptoms that lasted for >4 weeks from the onset of infection, and other variables were analyzed according to VDR genetic variants. In this study, ApaI and FokI polymorphisms showed no significant associations with COVID-19 severity (p > 0.05). However, a significant association was detected between the TaqI polymorphism and the severity of symptoms after infection with the SARS-CoV-2 virus (p = 0.04). The wild-type TaqI genotype was typically present in patients with mild illness, whereas the heterozygous TaqI genotype was present in asymptomatic patients. With regard to long-COVID-19 symptoms, the VDR heterozygous ApaI and wild-type TaqI genotypes were significantly associated with persistent fatigue and muscle pain after COVID-19 (p ˂ 0.05). Most carriers of the heterozygous ApaI genotype and carriers of the wild-type TaqI genotype reported experiencing fatigue and muscle pain that lasted for more than 1 month after the onset of COVID-19. Furthermore, the TaqI genotype was associated with persistent shortness of breath after COVID-19 (p = 0.003). Shortness of breath was more common among individuals with homozygous TaqI genotype than among individuals with the wild-type or heterozygous TaqI genotype. VDR TaqI is a possible genetic variant related to both COVID-19 severity and long-COVID-19 symptoms among Jordanian individuals. The associations between VDR TaqI polymorphisms and long-COVID-19 symptoms should be investigated in larger and more diverse ethnic populations.