Miracle-dz/UniFAR-FTUs huggingface dataset:
Removal of repressive histone marks creates epigenetic memory of recurring heat in Arabidopsis

Acclimation to high temperature increases plants’ tolerance of subsequent lethal high temperatures1-3. Although epigenetic regulation of plant gene expression is well studied, how plants maintain a memory of environmental changes over time remains unclear. Here, we show that JUMONJI (JMJ) proteins4-8, demethylases involved in histone H3 lysine 27 trimethylation (H3K27me3), are necessary for Arabidopsis thaliana heat acclimation. Acclimation induces sustained H3K27me3 demethylation at key HEAT SHOCK PROTEIN (HSP) loci by JMJs, poising the HSP genes for subsequent activation. Upon sensing heat after a 3-day interval, JMJs directly reactivate HSP genes. Finally, jmj mutants fail to maintain heat memory under fluctuating field temperature conditions. Our findings of an epigenetic memory mechanism involving histone demethylases may have implications for environmental adaptation of field plants.
Long-Term Dynamics Among Wolbachia Strains During Thermal Adaptation of Their Drosophila melanogaster Hosts

Climate change is a major evolutionary force triggering thermal adaptation in a broad range of species. While the consequences of global warming are being studied for an increasing number of species, limited attention has been given to the evolutionary dynamics of endosymbionts in response to climate change. Here, we address this question by studying the dynamics of Wolbachia, a well-studied endosymbiont of Drosophila melanogaster. D. melanogaster populations infected with 13 different Wolbachia strains were exposed to novel hot and cold laboratory environments for up to 180 generations. The short-term dynamics suggested a temperature-related fitness difference resulting in the increase of clade V strains in the cold environment only. Our long-term analysis now uncovers that clade V dominates in all replicates after generation 60 irrespective of temperature treatment. We propose that adaptation of the Drosophila host to either temperature or Drosophila C virus (DCV) infection are the cause of the replicated, temporally non-concordant Wolbachia dynamics. Our study provides an interesting case demonstrating that even simple, well-controlled experiments can result in complex, but repeatable evolutionary dynamics, thus providing a cautionary note on too simple interpretations on the impact of climate change.
CellExplorer: a graphical user interface and standardized pipeline for visualizing and characterizing single neuron features

The large diversity of neuron types of the brain, with numerous unique electrophysiological characteristics, provides the means by which cortical circuits perform complex operations. To quantify, compare and visualize the functional features of single neurons, we have developed a MATLAB-based framework, CellExplorer, consisting of three components: a processing module for extracting and calculating physiological metrics, a standardized yet flexible data structure, and a powerful graphical interface for fast manual curation and feature exploration. This data mining and discovery tool allows for inspection of dozens of computed features of neurons from large-scale recordings and relate them to those of other neurons in any combination at the speed of mouse clicks. The open source design of the CellExplorer permits the optimization of its functions tested against an ever-growing community-contributed database. CellExplorer will accelerate linking physiological properties of single neurons in the intact brain to genetically identified types.
POPULATION DYNAMICS AND PATTERN FORMATION IN THEORETICAL POPULATIONS

Simple individual-based models of population dynamics and spatial patterns are developed using cellular automata theory. These models assume that individuals within a population are distributed in space and that important interactions among individuals take place over some predefined local scale. Local density dependence in the model produces dynamics that depend on the scale of the dispersal distance. When dispersal occurs over long distances, the population enters a stable limit cycle. However, when colonization is limited to the same local neighborhood where competition is taking place, the spatial and temporal patterns become chaotic. Habitat size also affects the dynamics. Chaotic dynamics become cyclical as habitat size decreased. These results illustrate how a wide array of complex dynamics can arise with simple spatially distributed models and that the resulting dynamics can depend on the habitat size.
The Three Lipocalins of Egg-White: Only Ex-FABP Inhibits Siderophore-Dependent Iron Sequestration by Salmonella Enteritidis

Salmonella Enteritidis is the most prevalent food-borne pathogen associated with egg-related outbreaks in the European Union. During egg colonization, S. Enteritidis must resist the powerful anti-bacterial activities of egg white (EW) and overcome ovotransferrin-imposed iron-restriction (the most important anti-bacterial mechanism of EW). Many pathogens respond to iron restriction by secreting iron-chelating chemicals called siderophores but EW contains a siderophore-sequestering “lipocalin” protein (Ex-FABP) that is predicted to limit the usefulness of siderophores in EW. S. Enteritidis produces two siderophores: enterobactin, which is strongly bound by Ex-FABP; and the di-glucosylated enterobactin-derivative, salmochelin (a so-called “stealth” siderophore), which is not recognized by Ex-FABP. Thus, production of salmochelin may allow S. Enteritidis to escape Ex-FABP-mediated growth inhibition under iron restriction although it is unclear whether its EW concentration is sufficient to inhibit pathogens. Further, two other lipocalins (Cal-γ and α-1-ovoglycoprotein) are found in EW but their siderophore sequestration potential remains unexplored. In addition, the effect of EW lipocalins on the major EW pathogen, S. Enteritidis, has yet to be reported. We overexpressed and purified the three lipocalins of EW and investigated their ability to interact with the siderophores of S. Enteritidis, as well as their EW concentrations. The results show that Ex-FABP is present in EW at concentrations (5.1 μM) sufficient to inhibit growth of a salmochelin-deficient S. Enteritidis mutant under iron restriction but has little impact on the salmochelin-producing wildtype. Neither Cal-γ nor α-1-ovoglycoprotein bind salmochelin or enterobactin, nor do they inhibit iron-restricted growth of S. Enteritidis. However, both are present in EW at significant concentrations (5.6 and 233 μM, respectively) indicating that α-1-ovoglycoprotein is the 4th most abundant protein in EW, with Cal-γ and Ex-FABP at 11th and 12th most abundant. Further, we confirm the preference (16-fold) of Ex-FABP for the ferrated form (Kd of 5.3 nM) of enterobactin over the iron-free form (Kd of 86.2 nM), and its lack of affinity for salmochelin. In conclusion, our findings show that salmochelin production by S. Enteritidis enables this key egg-associated pathogen to overcome the enterobactin-sequestration activity of Ex-FABP when this lipocalin is provided at levels found in EW.
Characterization of Ancestral Origin of Cystic Fibrosis of Patients with New Reported Mutations in CFTR

The incidence of Cystic fibrosis (CF) and the frequency of the variants for CFTR depend on the population; furthermore, CF symptomatology is characterized by obstructive lung disease, pancreatic insufficiency among others, reliant on the individual genotype. Ecuadorian population is a mixture of Native Americans, Europeans, and Africans. That population admixture could be the reason for the new mutations reported in a previous study by Ruiz et al. (2019). A panel of 46 Ancestry Informative Markers was used to estimate the ancestral proportions of each available sample (12 samples in total). As a result, the Native American ancestry proportion was the most prevalent in almost all individuals, except for three patients from Guayaquil with the mutation [c.757G>A:p.Gly253Arg; c.1352G>T:p.Gly451Val] who had the highest European composition.
Using EEG microstates to examine post-encoding quiet rest and subsequent word-pair memory

Evidence suggests that the brain preferentially consolidates memories during “offline” periods, in which an individual is not performing a task and their attention is otherwise undirected, including spans of quiet, resting wakefulness. Moreover, research has demonstrated that factors such as the initial encoding strength of information influence which memories receive the greatest benefit. Recent studies have begun to investigate these periods of post-learning quiet rest using EEG microstate analysis to observe the electrical dynamics of the brain during these stretches of memory consolidation, specifically finding an increase in the amount of the canonical microstate D during a post-encoding rest period. Here, we implement an exploratory analysis to probe the activity of EEG microstates during a post-encoding session of quiet rest in order to scrutinize the impact of learning on microstate dynamics and to further understand the role these microstates play in the consolidation of memories. We examined 54 subjects (41 female) as they completed a word-pair memory task designed to use repetition to vary the initial encoding strength of the word-pair memories. In this study, we were able to replicate previous research in which there was a significant increase (p < .05) in the amount of microstate D (often associated with the dorsal attention network) during post-encoding rest. This change was accompanied by a significant decrease (p < .05) in the amount of microstate C (often associated with the default mode network). We also found preliminary evidence indicating a positive relationship between the amount of microstate D and improved memory for weakly encoded memories, which merits further exploration.
The Role of the Salmonella spvB IncF Plasmid and Its Resident Entry Exclusion Gene traS on Plasmid Exclusion

Salmonella enterica cause significant illnesses worldwide. There has been a marked increase in resistance to fluoroquinolones and β-lactams/cephalosporins, antibiotics commonly used to treat salmonellosis. However, S. enterica serovars vary in their resistance to these and other antibiotics. The systemic virulence of some Salmonella serovars is due to a low copy number, IncF plasmid (65–100 kb) that contains the ADP-ribosylating toxin, SpvB. This virulence plasmid is present in only nine Salmonella serovars. It is possible that the spvB-virulence plasmid excludes other plasmids and may explain why antibiotic resistance is slow to develop in certain Salmonella serovars such as S. Enteritidis. The distribution of plasmid entry exclusion genes traS/traT and traY/excA are variable in Salmonella IncF and IncI plasmids, respectively and may account for differences in emergent antimicrobial resistance for some Salmonella serovars. The goal of this study is to determine the contribution of the Salmonella spvB-virulence plasmid in F-plasmid exclusion. From conjugation experiments, S. Typhimurium exhibited lower conjugation frequency with incFI and incFII plasmids when the spvB-virulence plasmid is present. Furthermore, introduction of cloned incFI traS into a “plasmidless” S. Typhimurium LT2 strain and Escherichia coli DH5α excluded incFI plasmid. However, deletion of the virulence plasmid traS did not affect plasmid exclusion significantly compared to a spvB control deletion. In addition, differences in F plasmid conjugation in natural Salmonella isolates did not correlate with IncF or SpvB-virulence plasmid genotype. There appear to be other plasmid or chromosomal genes at play in plasmid exclusion that may be responsible for the slow development of antibiotic resistance in certain serovars.
Birdsong sequence exhibits long context dependency comparable to human language syntax

Context dependency is a key feature in sequential structures of human language, which requires reference between words far apart in produced sequence. Assessing how long the past context has effect on the current status provides crucial information to understand the mechanism for complex sequential behaviors. Birdsongs serve as a representative model for studying the context dependency in sequential signals produced by non-human animals, while previous reports were upper bounded by methodological limitations. Here we show that birdsongs have a long context dependency comparable to grammatical structure in human language. We newly estimated the context dependency in birdsongs in a scalable way using a neural-network-based language model whose accessible context length is sufficiently long. Quantitative comparison with the parallel analysis of English sentences revealed that the context dependency in the birdsong was much shorter than that in the sentence, but was comparable to the grammatical structure when semantic factors were removed. Our findings are in accordance with the previous generalization in comparative studies that birdsong is more homologous to human language syntax than the entirety of human language including semantics.
Quality of Life in Papillary Thyroid Microcarcinoma Patients Undergoing Radiofrequency Ablation or Surgery: A Comparative Study

Objective: Papillary thyroid microcarcinoma (PTMC) has a good prognosis and a long survival time. Health-related quality of life (HRQoL) is vital for PTMC patients during their survivorship. Ultrasound (US)-guided radiofrequency ablation (RFA), which has high efficacy and safety, is recommended as an alternative treatment to surgery for the patients with low-risk PTMC. However, the assessment of QoL of patients with PTMC has not been specially reported. The purpose of our study was to compare the HRQoL of patients with PTMC who underwent RFA and those who underwent surgery. Methods: From October 2019 to December 2019, 88 PTMC patients were enrolled in our study, including 54 in RFA group and 34 in surgery group. We used three questionnaires which included the 36-item short form health survey (SF-36), thyroid cancer-specific quality of life (THYCA-QOL), and Fear of Progression Questionnaire-Short Form (FoP-Q-SF) for each patient to evaluate their scores of HRQoL. The scores were compared after adjusting for age, sex, medical expense, and follow-up time. Results: According to the SF-36, the scores of the domain for the role limitation due to physical problems and emotional problems (RP, RE) as well as Physical Component Summary (PCS) showed a significant negative linear association between the RFA group and surgery group: RP coefficient [coef]−22.613 [confidence interval (CI) −33.504 to −11.723], p < 0.001, RE (coef: −21.901 [CI −36.737 to −7.064], p = 0.004), and PCS (coef: −8.312 [CI −13.694 to −2.930], p = 0.003). The THYCA-QOL showed that the scores of the surgery group were higher than that of the RFA group regarding scars (coef: 10.246 [CI 1.330 to 19.162], p = 0.025 according to the multivariate analysis), suggesting a higher level of complaint in the surgery group. There was no statistically significant difference in the scores of FoP-Q-SF between the two groups. Conclusions: In patients with PTMC, US-guided RFA offers advantage over surgery in terms of HRQoL, which supports the role of RFA as an alternative strategy to surgery.
Pattern recognition receptors confer plant salt tolerance via WRKY18/WRKY40 transcription factors

Pattern recognition receptors (PRRs) bind microbe- and damage-associated molecular patterns (MAMPs/DAMPs, respectively) to enhance host immunity in animals and plants. Here, we report that PRRs also confer salt tolerance in the model plant Arabidopsis thaliana following recognition of cognate ligands, such as bacterial flagellin and EF-Tu and the endogenous Pep peptides. Pattern-triggered salt tolerance (PTST) requires the PRR-associated kinases BAK1 and BIK1, and the NADPH oxidase RBOHD. Transcriptome profiling reveals an inventory of PTST target genes, which increase or acquire salt responsiveness following an exposure to immunogenic patterns. In their regulatory DNA sequences, specific binding sites for a subset of WRKY transcription factors are over-represented. Accordingly, PTST requires WRKY40 and WRKY18, which activate salt tolerance-related genes but attenuate pathogen defense-related genes, including the EDS1 immunity activator. PRR signaling leads to sustained WRKY40/WRKY18 accumulation under salt stress and utilizes both WRKYs for salt tolerance. The PRR-WRKY40/WRKY18 module also confers salt tolerance after challenge with non-pathogenic bacteria. Our findings give molecular insight into signaling plasticity underlying biotic-abiotic stress cross-tolerance in plants conferred by PRRs.
Labeling subcellular structures in living specimens using live-cell incompatible dyes with excellent optical properties

Despite the urgent needs of imaging living specimens for cutting-edge biological research, most of the existing fluorescent labeling methods suffer from either poor optical properties or complicated operations to realize cell-permeability and specificity. Here, we introduce a method to overcome this tradeoff by incubating living cells and tissues with fluorescent dyes, no matter if they are cell-permeable or not, at particular conditions (concentration and temperature) without physical cell-penetration or chemical modifications. Based on this method, the mitochondrial labeling capability of Atto dyes, especially Atto 647N with extraordinary optical properties, together with interesting interactions between organelles is revealed. These results indicate the great potential of using dyes, which are normally considered “live-cell incompatible”, to capture the morphology and dynamics of subcellular structures in living specimens.
Flagellar targeting of an arginine kinase requires a conserved lipidated protein intraflagellar transport (LIFT) pathway in Trypanosoma brucei

Both intraflagellar transport (IFT) and lipidated protein intraflagellar transport (LIFT) pathways are essential for cilia/flagella biogenesis, motility, and sensory functions. In the LIFT pathway, lipidated cargoes are transported into the cilia through the coordinated actions of cargo carrier proteins such as Unc119 or PDE6δ, as well as small GTPases Arl13b and Arl3 in the cilium. Our previous studies have revealed a single Arl13b ortholog in the evolutionarily divergent Trypanosoma brucei, the causative agent of African sleeping sickness. TbArl13 catalyzes two TbArl3 homologs, TbArl3A and TbArl3C, suggesting the presence of a conserved LIFT pathway in these protozoan parasites. Only a single homolog to the cargo carrier protein Unc119 has been identified in T. brucei genome, but its function in lipidated protein transport has not been characterized. In this study, we exploited the proximity-based biotinylation approach to identify binding partners of TbUnc119. We showed that TbUnc119 binds to a flagellar arginine kinase TbAK3 in a myristoylation-dependent manner and is responsible for its targeting to and enrichment in the flagellum. Interestingly, only TbArl3A, but not TbArl3C interacted with TbUnc119 in a GTP-dependent manner, suggesting functional specialization of Arl3-GTPases in T. brucei. These results establish the function of TbUnc119 as a myristoylated cargo carrier and support the presence of a conserved LIFT pathway in T. brucei.
Enhanced inter-regional coupling of neural responses underlies long-term behavioral priming

Stimulus identification commonly improves with repetition over long delays (“repetition priming”), whereas neural activity commonly decreases (“repetition suppression”). Multiple models have been proposed to explain this brain-behavior relationship, predicting alterations in functional and/or effective connectivity (Synchrony and Predictive Coding models), in the latency of neural responses (Facilitation model), and in the relative similarity of neural representations (Sharpening model). Here, we test these predictions with fMRI during overt and covert naming of repeated and novel objects. While we find partial support for predictions of the Facilitation and Sharpening models in the left fusiform gyrus and left frontal cortex, the strongest support was observed for the Synchrony model, with increased coupling between right temporoparietal and anterior cingulate cortex for repeated objects that correlated with priming magnitude across participants. Despite overlap with regions showing repetition suppression, increased coupling and repetition suppression varied independently, establishing that they follow from distinct mechanisms. Highlights Tested four prominent neural models of repetition suppression and long-term priming Connectivity analyses supported Synchrony model but not Predictive Coding model Timing, spatial similarity of responses partially support Facilitation, Sharpening Repetition suppression was independent of coupling, implying distinct mechanisms eTOC Gotts et al. test four prominent neural models of repetition suppression and behavioral priming. They show that the model with the most support is the Synchrony model: a whole-brain connectivity analysis revealed that temporoparietal cortex has increased coupling with anterior cingulate cortex following repetition, particularly for strongly primed objects.
Rational design of human cathepsin L with efficient collagenolytic activity

Collagens are the main structural components of ECM and collagenolysis is vital for ECM remodelling, which is essential for normal organ homeostasis. Any dysregulation of this process can result in various pathological conditions. The degradation of the interstitial collagens is generally mediated by specific collagenases which are capable of cleaving at specific loci in the collagen triple helix. Lysosomal cysteine cathepsins have general housekeeping as well as some highly specialized functions. Amongst them, human cathepsin K is the only lysosomal cysteine protease which has potent collagenolytic activity against type I collagen. In this study, we have imparted collagenolytic property to another human cysteine protease, cathepsin L, by systematically engineering proline-specificity and GAG-binding surface in the protease. The designed proline-specific mutant shows high specificity for peptidyl substrate containing proline at P2 position but is incapable of cleaving collagen. However, when the proline-specific mutant is further engineered for GAG-binding surface, it can degrade type I collagen in presence of Chondroitin 4-Sulfate (C4-S). We also present high resolution crystal structures of these proline-specific (1.4 Å) and collagen-specific (1.8 Å) mutants. Finally docking studies with prolyl-peptidic substrate (Ala-Gly-Pro-Arg-Ala) at the active site and a GAG molecule (C4-S) at the GAG binding site enables us to identify key structural features responsible for collagenolytic activity of papain-like cysteine proteases. This study provides a rational approach to engineer an efficient collagenase from a human template enzyme which may have various noninvasive therapeutic implications with an expected additional advantage of immuno-compatiblity.