Miracle-dz/UniFAR-FTUs huggingface dataset:
Flavonols contrary affect the interconnected glucosinolate and camalexin biosynthesis pathway in Arabidopsis thaliana

Flavonols are structurally and functionally diverse molecules playing roles in plant biotic and abiotic stress tolerance, auxin transport inhibition, pollen development, etc. Despite their ubiquitous occurrence in land plants and multifunctionality, the effect of perturbation of flavonol biosynthesis over global gene expression and pathways other than flavonoid biosynthesis has not been studied in detail. To understand the signaling role of different flavonol metabolites, herein, we used the flavonol deficient Arabidopsis thaliana loss-of-function mutant flavonol synthase1 (fls1-3) as object of study. Comparative transcriptome and metabolic profiling were used to study the effects of genetic flavonol deficiency and exogenous supplementation with flavonol derivatives (kaempferol, quercetin and rutin) on different cellular processes in the seedling. Various flavonol biosynthesis-related regulatory and structural genes were found to be up-regulated in the fls1-3 mutant which could be reversed by exogenous flavonol feeding. Our manifold comparative studies indicated the modulation of various biological processes and metabolic pathways by flavonols. Camalexin biosynthesis was found to be negatively regulated by flavonols. Interestingly, flavonols appeared to promote the accumulation of aliphatic glucosinolate through transcription factor-mediated up-regulation of biosynthesis genes. Overall, this study provides new insights into molecular mechanisms by which flavonols interfere with the relevant signal chains and their molecular targets and adds new knowledge to the expanding plethora of biological activity of flavonols in plants. Significance Comparative transcriptome and metabolomic profiling of genetic flavonol deficiency and exogenous flavonol supplementation in A. thaliana seedlings, for the first-time revealed the inverse regulation of interconnected specialized metabolite pathways by flavonol aglycones, and -glycosides. Flavonols negatively regulate camalexin biosynthesis, while promoting the accumulation of aliphatic glucosinolates. Our study adds new insights into the expanding plethora of biological activity of flavonols in plants and will help to uncover the molecular mechanisms by which flavonols interfere with the relevant signal chains and their molecular targets.
A novel CLAVATA1 mutation causes multilocularity in Brassica rapa

Locules are the seed-bearing structure of fruits. Multiple locules are associated with increased fruit size and seed set, and therefore control of locule number is an important agronomic trait. Locule number is controlled in part by the CLAVATA-WUSCHEL pathway. Disruption of either the CLAVATA1 receptor-like kinase or its ligand CLAVATA3 can cause larger floral meristems and an increased number of locules. In an EMS mutagenized population of Brassica rapa, we identified a mutant allele that raises the number of locules from 4 to a range of from 6 to 8. Linkage mapping and genetic analysis support that the mutant phenotype is due to a missense mutation in a CLAVATA 1 (CLV1) homolog. In addition to increased locule number, brclv1 individuals fail to terminate their floral meristems, resulting in internal gynoecia that negatively impact seed production.
Learning with phenotypic similarity improves the prediction of functional effects of missense variants in voltage-gated sodium channels

Background Missense variants in genes encoding voltage-gated sodium channels are associated with a spectrum of severe diseases affecting neuronal and muscle cells, the so-called sodium channelopathies. Variant effects on the biophysical function of the channel correlate with clinical features and can in most cases be categorized as an overall gain- or loss-of-function. This information enables a timely diagnosis, facilitates precision therapy, and guides prognosis. Machine learning models may be able to rapidly generate supporting evidence by predicting variant functional effects. Methods Here, we describe a novel multi-task multi-kernel learning framework capable of harmonizing functional results and structural information with clinical phenotypes. We included 62 sequence- and structure-based features such as amino acid physiochemical properties, substitution radicality, conservation, protein-protein interaction sites, expert annotation, and others. We harmonized phenotypes as human phenotype ontology (HPO) terms, and compared different measures of phenotypic similarity under simulated sparsity or noise. The final model was trained on whole-cell patch-clamp recordings of 375 unique non-synonymous missense variants each expressed in mammalian cells. Results Our gain- or loss-of-function classifier outperformed both conventional baseline and state-of-the-art methods on internal validation (mean accuracy 0.837 ± 0.035, mean AU-ROC 0.890 ± 0.023) and on an independent set of recently described variants (n = 30, accuracy 0.967, AU-ROC 1.000). Model performance was robust across different phenotypic similarity measures and largely insensitive to phenotypic noise or sparsity. Localized multi-kernel learning offered biological insight and interpretability by highlighting channels with implicit genotype-phenotype correlations or latent task similarity for downstream analysis. Conclusions Learning with phenotypic similarity makes efficient use of clinical information to enable accurate and robust prediction of variant functional effects. Our framework extends the use of human phenotype ontology terms towards kernel-based methods in machine learning. Training data, pre-trained models, and a web-based graphical user interface for the model are publicly available.
Properties of young pulsar wind nebulae: TeV detectability and pulsar properties

Among dozens young pulsar wind nebulae, some have been detected in TeV \gamma-rays (TeV PWNe), while others have not (non-TeV PWNe). The TeV emission detectability is not correlated either with the spin-down power or with the characteristic age of their central pulsars, and it is an open problem what determines the detectability. To study this problem, we investigate spectral evolution of five young non-TeV PWNe, 3C58, G310.6-1.6, G292.0+1.8, G11.2-0.3 and SNR B0540-69.3. We use a spectral evolution model which has been developed to be applied to young TeV PWNe in our previous works. TeV \gamma-ray flux upper limits of non-TeV PWNe give upper or lower limits on parameters, such as the age of the PWN and the fraction of the spin-down power going to the magnetic energy injection (the fraction parameter). Combined with other independent observational and theoretical studies, we can guess a plausible value of the parameters for each object. For 3C58, we prefer the parameters with an age of 2.5 kyr old and the fraction parameter of 3.0x10^{-3}, although the spectral modeling alone does not rule out a shorter age and a higher fraction parameter. The fraction parameter of 3.0x10^{-3} is also consistent for other non-TeV PWNe and then the value is regarded as common to young PWNe including TeV PWNe. Moreover, we find that the intrinsic properties of the central pulsars are similar, 10^{48-50}erg for the initial rotational energy and 10^{42-44}erg for the magnetic energy (2x10^{12} - 3x10^{13}G for the dipole magnetic field strength at their surfaces). The TeV detectability is correlated with the total injected energy and the energy density of the interstellar radiation field around PWNe. Except for G292.0+1.8, a broken power-law injection of the particles well reproduces the broadband emission from non-TeV PWNe.
Diversification of neuropil organization in specialized and broadly 1 tuned olfactory glomerular circuits in Drosophila melanogaster 2 3

Diversification of neuropil organization in specialized and broadly 1 tuned olfactory glomerular circuits in Drosophila melanogaster 2 3 Lydia Gruber1, Rafael Cantera2, Markus William Pleijzier3, Bill S. Hansson1#, Jürgen 4 Rybak 1# 5 6 1 Max Planck Institute for Chemical Ecology, Department of Evolutionary Neuroethology, 07745 Jena, Germany 7 2 Instituto de Investigaciones Biológicas Clemente Estable, Departamento de Biología del Neurodesarrollo, 11600 8 Montevideo, Uruguay 9 3 Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, England, United Kingdom 10 11 # contributed equally 12 13 *Correspondence: Jürgen Rybak, jrybak@ice.mpg. de 14 15
Production of selenium nanoparticles occurs through an interconnected pathway of sulphur metabolism and oxidative stress response in Pseudomonas putida KT2440

The soil bacterium Pseudomonas putida KT2440 has been shown to produce selenium nanoparticles aerobically from selenite; however, the molecular actors involved in this process are unknown. Here, through a combination of genetic and analytical techniques, we report the first insights into selenite metabolism in this bacterium. Our results suggest that the reduction of selenite occurs through an interconnected metabolic network involving central metabolic reactions, sulfur metabolism, and the response to oxidative stress. Genes such as sucA, D2HGDH and PP_3148 revealed that the 2-ketoglutarate and glutamate metabolism is important to converting selenite into selenium. On the other hand, mutants affecting the activity of sulfite reductase reduced the bacteria’s ability to transform selenite. Other genes related to sulfur metabolism (ssuEF, sfnCE, sqrR, sqr and pdo2) and stress response (gqr, lsfA, ahpCF and sadI) were also identified as involved in selenite transformations. Interestingly, suppression of genes sqrR, sqr and pdo2 resulted in the production of selenium nanoparticles at a higher rate than the wild-type strain, which is of biotechnological interest. The data provided in this study brings us closer to understanding the metabolism of selenium in bacteria, and offers new targets for the development of biotechnological tools for the production of selenium nanoparticles.
Treenome Browser: co-visualization of enormous phylogenies and millions of genomes

Treenome Browser is a web browser tool to interactively visualize millions of genomes alongside huge phylogenetic trees. Availability and Implementation Treenome Browser for SARS-CoV-2 can be accessed at cov2tree.org, or at taxonium.org for user-provided trees. Source code and documentation are available at github.com/theosanderson/taxonium and docs.taxonium.org/en/latest/treenome.html. Contact alex.kramer@ucsc.edu, rucorbet@ucsc.edu
Including both sexes in in vivo research does not necessitate an increase in sample size: a key role for factorial analysis methods

In recent years, there has been a strong drive to improve the inclusion of animals of both sex during in vivo research, driven by a need to improve sex representation in fundamental biology and drug development. This has resulted in inclusion mandates by funding bodies and journals, alongside numerous published manuscripts highlighting the issue and providing guidance to scientists. However, progress is slow and blockers to the routine use of both sexes remain. From a statistical and experimental design perspective, concerns include difficulty selecting and conducting an appropriate analysis and the perceived need for a higher sample size to achieve an equivalent level of statistical power. When both sexes are included, analysis errors are frequent, including inappropriate pooling or sex-disaggregation of the data. These mistakes result in a failure to properly account for the variation in the data that arises from sex, and subsequently lead to poor inference regarding the biological impact of sex. The purpose of this manuscript is to address frequently cited blockers and analysis errors, thus providing a practical guide to support scientists in the design of in vivo studies which include both sexes. Primarily, we demonstrate that there is no loss of power to detect treatment effects when splitting the sample size across sexes in most common biological scenarios, providing that the data are analysed appropriately. In the rare situations where power is lost, the benefit of understanding the role of sex outweighs the power considerations. When estimating a generalisable translatable effect, where exploring sex differences are not the primary scientific objective, we recommend splitting the sample size across male and female mice as a standard strategy. We also demonstrate an optimal analysis pipeline for analysing data gathered using both sexes which is designed to help address common analysis errors.
Single-nucleus RNA-seq reveals that MBD5, MBD6, and SILENZIO maintain silencing during epigenetic reprogramming in pollen

Silencing of transposable elements (TEs) drove the evolution of numerous redundant mechanisms of transcriptional regulation. Arabidopsis MBD5, MBD6, and SILENZIO act as TE repressors downstream of DNA methylation. Here we show via single-nucleus RNA-seq of developing male gametophytes that these repressors are critical for TE silencing in the pollen vegetative cell, which undergoes epigenetic reprogramming causing chromatin decompaction to support fertilization by sperm cells. Instead, other silencing mutants (met1, ddm1, mom1, morc) show loss of silencing in all pollen nucleus types and somatic cells. We found that TEs repressed by MBD5/6 gain accessibility in wild-type vegetative nuclei despite remaining silent, suggesting that loss of DNA compaction makes them sensitive to loss of MBD5/6. Consistently, crossing mbd5/6 to histone 1 mutants, which have decondensed chromatin in leaves, reveals derepression of MBD5/6-dependent TEs in leaves. MBD5/6 and SILENZIO thus act as a silencing system especially important when chromatin compaction is compromised.
Multiomics reveal that silk fibroin and sericin differentially potentiate the paracrine functions of mesenchymal stem cells and enhance tissue regeneration

Silk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials that show great potential in regenerative medicine. However, their biochemical interactions with stem cells were not fully understood. Here, we employed multiomics to obtain a global view of the triggered cellular processes and pathways of MSCs by SF and SS. Integrated RNA-seq and proteomics revealed that SF and SS strongly enhanced the paracrine activity of MSCs through differentially activating integrin and glycolytic pathways, rather than directly regulating stem cell fate to initiate multiple but distinct biological processes in MSCs. Those specific paracrine signals of MSCs stimulated by SF and SS effectively promoted skin wound healing by influencing the behaviors of multiple resident cells in skin wound microenvironments. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling future development of silk-based therapeutics for tissue engineering and stem cell therapy.
Molecular Environments of Supernova Remnants†

Abstract There are about 70 Galactic supernova remnants (SNRs) that are now confirmed or suggested to be in physical contact with molecular clouds (MCs) with six kinds of evidence of multiwavelength observations. Recent detailed CO-line spectroscopic mappings of a series of SNRs reveal them to be in cavities of molecular gas, implying the roles the progenitors may have played. We predict a linear correlation between the wind bubble sizes of main-sequence OB stars in a molecular environment and the stellar masses and discuss its implication for supernova progenitors. The molecular environments of SNRs can serve as a good probe for the γ-rays arising from the hadronic interaction of the accelerated protons, and this paper also discusses the γ-ray emission from MCs illuminated by diffusive protons that escape from SNR shocks.
Influenza A Virus Exacerbates Group A Streptococcus Infection and Thwarts Anti-Bacterial Inflammatory Responses in Murine Macrophages

Seasonal influenza epidemics pose a considerable hazard for global health. In the past decades, accumulating evidence revealed that influenza A virus (IAV) renders the host vulnerable to bacterial superinfections which in turn are a major cause for morbidity and mortality. However, whether the impact of influenza on anti-bacterial innate immunity is restricted to the vicinity of the lung or systemically extends to remote sites is underexplored. We therefore sought to investigate intranasal infection of adult C57BL/6J mice with IAV H1N1 in combination with bacteremia elicited by intravenous application of Group A Streptococcus (GAS). Co-infection in vivo was supplemented in vitro by challenging murine bone marrow derived macrophages and exploring gene expression and cytokine secretion. Our results show that viral infection of mice caused mild disease and induced the depletion of CCL2 in the periphery. Influenza preceding GAS infection promoted the occurrence of paw edemas and was accompanied by exacerbated disease scores. In vitro co-infection of macrophages led to significantly elevated expression of TLR2 and CD80 compared to bacterial mono-infection, whereas CD163 and CD206 were downregulated. The GAS-inducible upregulation of inflammatory genes, such as Nos2, as well as the secretion of TNFα and IL-1β were notably reduced or even abrogated following co-infection. Our results indicate that IAV primes an innate immune layout that is inadequately equipped for bacterial clearance.
Context-dependent neural effects predict mind wandering minutes in advance

Mind wandering occurs when spontaneous thought generation increases while cognitive control decreases. These are complex psychological events involving multiple brain systems, notably the default-mode (DMN) network and an antagonist system of cognitive control/frontoparietal attention networks, which are here addressed collectively as goal-directed networks (GDN). As opposed to the task-positivity of GDN, DMN exhibits largely task-negative effects. However, DMN could become task-positive when endogenous thoughts dominate. We hypothesized that a switch from task-negativity to positivity could be a factor in the transition between task-focused and mind wandering states. We estimated stochastic causality of the DMN-and GDN activity on mind wandering behavior, in a tone counting task designed to induce mind wandering in healthy adult participants. Electroencephalogram (EEG) was recorded together with subjective reports of mind wandering and other psychological and behavioral measures. Stochastic causality was found between measures of DMN activity (alpha-band power) and cognitive control (% correct of the task) prior to both task focused and mind wandering behavior. The estimated delay of the neural effect on the behavioral measure was 4-10 min. The effect was task-negative in task focused, but positive in mind wandering conditions. The results suggest that DMN slowly but dynamically influences cognitive control, through which the transition from task focused to mind wandering behavior is effectuated. Pillai used to estimate statistical significance of the difference between the fits of the full and reduced models. The 100 comparisons for 2 reduced models yielded 200 tests. The R implementation of Pillai provides the estimated F-statistic with corresponding probability. We corrected for Type-I errors over the 200 tests by using the FDR method. An arbitrary threshold (p<0.01) was applied to the corrected probability, to attribute stochastic causality to the neural effect. The indices k and reveal the timing of the effect, e.g., a stochastically causal effect of 𝐴𝑙𝑝ℎ𝑎 𝑡−𝑘 at k=4 to 𝑁𝑜𝑇𝑠 𝑡 suggests that the 2min interval of data bin) the neural activity between 6-8min before the report of the high (or low) had stochastically causal to the number of spontaneous The above results show that Alpha activity 6-10min before the high %MW report had a stochastically causal and task- positive effect to the %CC. The rest of neural effects did not show notable contribution to predict the %CC and NoTs. The above results show that Alpha activity 4-6min before the low %MW report had a stochastically causal and task- negative effect on %CC. Moreover, the results show that the Alpha activity correlated without delay (in the current time scale), positively with %CC, while negatively with NoTs in the low %MW segment.
The low Sr/Ba ratio on some extremely metal-poor stars

It has been noted that, in classical extremely metal-poor (EMP) stars, the abundance ratio of Sr and Ba, is always higher than [Sr/Ba] = -0.5, the value of the solar r-only process; however, a handful of EMP stars have recently been found with a very low Sr/Ba ratio. We try to understand the origin of this anomaly by comparing the abundance pattern of the elements in these stars and in the classical EMP stars. Four stars with very low Sr/Ba ratios were observed and analyzed within LTE approximation through 1D (hydrostatic) model atmosphere, providing homogeneous abundances of nine neutron-capture elements. In CS 22950-173, the only turnoff star of the sample, the Sr/Ba ratio is, in fact, found to be higher than the r-only solar ratio, so the star is discarded. The remaining stars (CS 29493-090, CS 30322-023, HE 305-4520) are cool evolved giants. They do not present a clear carbon enrichment. The abundance patterns of the neutron-capture elements in the three stars are strikingly similar to a theoretical s-process pattern. This pattern could at first be attributed to pollution by a nearby AGB, but none of the stars presents a clear variation in the radial velocity indicating the presence of a companion. The stellar parameters seem to exclude any internal pollution in a TP-AGB phase for at least two of these stars. The possibility that the stars are early-AGB stars polluted during the core He flash does not seem compatible with the theory.
N-Body Simulations for Coupled Scalar Field Cosmology

We describe in detail the general methodology and numerical implementation of consistent N-body simulations for coupled-scalar-field models, including background cosmology and the generation of initial conditions (with the different couplings to different matter species taken into account). We perform fully consistent simulations for a class of coupled-scalar-field models with an inverse power-law potential and negative coupling constant, for which the chameleon mechanism does not work. We find that in such cosmological models the scalar-field potential plays a negligible role except in the background expansion, and the fifth force that is produced is proportional to gravity in magnitude, justifying the use of a rescaled gravitational constant G in some earlier N-body simulation works for similar models. We then study the effects of the scalar coupling on the nonlinear matter power spectra and compare with linear perturbation calculations to see the agreement and places where the nonlinear treatment deviates from the linear approximation. We also propose an algorithm to identify gravitationally virialized matter halos, trying to take account of the fact that the virialization itself is also modified by the scalar-field coupling. We use the algorithm to measure the mass function and study the properties of dark-matter halos. We find that the more » net effect of the scalar coupling helps produce more heavy halos in our simulation boxes and suppresses the inner (but not the outer) density profile of halos compared with the {Lambda}CDM prediction, while the suppression weakens as the coupling between the scalar field and dark-matter particles increases in strength. « less