bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-range organization of primary intestinal fibroblasts guides directed and persistent migration of organoid-derived intestinal epithelia
Authors: Fernández-Majada Vanesa , Comelles Jordi , Abad-Lázaro Aina , Acevedo Verónica , Esteve-Codina Anna , Hernando-Momblona Xavier , Batlle Eduard , Martinez Elena 
Published: May 2021

AbstractFibroblasts reside underneath most epithelial tissues. In the intestine, their role has been mostly restricted to a secretory and supportive role. Recent studies have shown that fibroblasts’ migration is key during vilification and wound healing. Yet, whether interactions between epithelial cells with fibroblasts and with the matrix contribute to epithelial movement remains elusive. Here, we show that intestinal fibroblasts enhance the directed and persistent migration of organoid-derived intestinal epithelia. By using a novel gap closurein vitromodel of the intestinal mucosa that includes both the epithelium and the stromal compartments, we demonstrate that the physical presence of fibroblasts in contact with the epithelium plays a crucial role in epithelial restoration by enhancing epithelial tissue integrity. Our results demonstrate that fibroblasts undergo long-range ordering to align perpendicularly to the epithelial migrating front, and deposit protein paths that act as contact guidance features to direct epithelial migration. In turn, only the physical interaction of intestinal fibroblasts with intestinal organoids drives epithelial spreading in three dimensions. Our results demonstrate that fibroblasts actively coordinate to accelerate intestinal epithelial restoration.
Multi-omics analysis of xylem sap uncovers dynamic modulation of poplar defenses by ammonium and nitrate
Authors: Kasper Karl , Abreu Ilka N , Feussner Kirstin , Zienkiewicz Krzysztof , Herrfurth Cornelia , Ischebeck Till , Janz Dennis , Majcherczyk Andrzej , Schmitt Kerstin , Valerius Oliver , Braus Gerhard H. , Feussner Ivo , Polle Andrea 
Published: May 2021

SummaryXylem sap is the major transport route for nutrients from roots to shoots. Here, we investigated how variations in nitrogen (N) nutrition affected the metabolome and proteome of xylem sap, growth of the xylem endophyte Brennaria salicis and report transcriptional re-wiring of leaf defenses in poplar (Populus x canescens). We supplied poplars with high, intermediate or low concentrations of ammonium or nitrate. We identified 288 unique proteins in xylem sap. About 85% of the xylem sap proteins were shared among ammonium- and nitrate-supplied plants. The number of proteins increased with increasing N supply but the major functional categories (catabolic processes, cell wall-related enzymes, defense) were unaffected. Ammonium nutrition caused higher abundances of amino acids and carbohydrates, while nitrate caused higher malate levels in xylem sap. Pipecolic acid and N-hydroxy-pipecolic acid increased whereas salicylic acid and jasmonoyl-isoleucine decreased with increasing N nutrition. Untargeted metabolome analyses revealed 2179 features in xylem sap, of which 863 were differentially affected by N treatments. We identified 122 metabolites, mainly from specialized metabolism of the groups of salicinoids, phenylpropanoids, phenolics, flavonoids, and benzoates. Their abundances increased with decreasing N. Endophyte growth was stimulated in xylem sap of high N- and suppressed in that of low N-fed plants. The drastic changes in xylem sap composition caused massive changes in the transcriptional landscape of leaves and recruited defense pathways against leaf feeding insects and biotrophic fungi, mainly under low nitrate. Our study uncovers unexpected complexity and variability of xylem composition with consequences for plant defenses.Significance statementThis study reports the largest, currently available plant xylem sap proteome and metabolome databases and highlights novel discoveries of specialized metabolites and phytohormones in the xylem sap. This is the first multi-omics study linking differences in nitrogen supply with changes xylem sap composition, endophyte growth and transcriptional defenses in leaves.
PandemicVibrio choleraeAcquired Competitive Traits from an EnvironmentalVibrioSpecies
Authors: Santoriello Francis J. , Kirchberger Paul C. , Boucher Yann , Pukatzki Stefan 
Published: May 2021

ABSTRACTBackgroundVibrio cholerae,the causative agent of cholera, is a human pathogen that thrives in estuarine environments.V. choleraecompetes with neighboring microbes by the contact-dependent translocation of toxic effectors with the type VI secretion system (T6SS). Effector types are highly variable acrossV. choleraestrains, but all pandemic isolates encode the same set of distinct effectors. It is possible that acquisition of these effectors via horizontal gene transfer played a role in the development of pandemicV. cholerae.ResultsWe assessed the distribution ofV. choleraeT6SS loci across multipleVibriospecies. We showed that the fish-pathogenV. anguillarumencodes all threeV. choleraecore loci as well as two of the four additional auxiliary clusters. We further demonstrated thatV. anguillarumshares T6SS effectors withV. cholerae,including every pandemic-associatedV. choleraeeffector. We identified a novel T6SS cluster (Accessory Aux1) that is widespread inV. anguillarumand encodes the pandemicV. choleraeeffector TseL. We highlighted potential gene transfer events of Accessory Aux1 fromV. anguillarumtoV. cholerae.Finally, we showed that TseL fromV. choleraecan be neutralized by theV. anguillarumAccessory Aux1 immunity protein and vice versa, indicatingV. anguillarumas the donor oftseLto theV. choleraespecies.ConclusionsV. anguillarumconstitutes an environmental reservoir of pandemic-associatedV. choleraeT6SS effectors.V. anguillarumandV. choleraelikely share an environmental niche, compete, and exchange T6SS effectors. Further, our findings highlight the fish as a potential reservoir of pandemicV. cholerae.
SARS-CoV-2 transmission via apical syncytia release from primary bronchial epithelia and infectivity restriction in children epithelia
Authors: Beucher Guillaume , Blondot Marie-Lise , Celle Alexis , Pied Noémie , Recordon-Pinson Patricia , Esteves Pauline , Faure Muriel , Métifiot Mathieu , Lacomme Sabrina , Dacheaux Denis , Robinson Derrick , Längst Gernot , Beaufils Fabien , Lafon Marie-Edith , Berger Patrick , Landry Marc , Malvy Denis , Trian Thomas , Andreola Marie-Line , Wodrich Harald 
Published: May 2021

AbstractThe beta-coronavirus SARS-CoV-2 is at the origin of a persistent worldwide pandemic. SARS-CoV-2 infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract eventually causing acute severe respiratory syndrome with a high degree of mortality in the elderly. Here we use reconstituted primary bronchial epithelia from adult and children donors to follow the infection dynamic following infection with SARS-CoV-2. We show that in bronchial epithelia derived from adult donors, infections initiate in multi-ciliated cells. Then, infection rapidly spread within 24-48h throughout the whole epithelia. Within 3-4 days, large apical syncytia form between multi-ciliated cells and basal cells, which dissipate into the apical lumen. We show that these syncytia are a significant source of the released infectious dose. In stark contrast to these findings, bronchial epithelia reconstituted from children donors are intrinsically more resistant to virus infection and show active restriction of virus spread. This restriction is paired with accelerated release of IFN compared to adult donors. Taken together our findings reveal apical syncytia formation as an underappreciated source of infectious virus for either local dissemination or release into the environment. Furthermore, we provide direct evidence that children bronchial epithelia are more resistant to infection with SARS-CoV-2 providing experimental support for epidemiological observations that SARS-CoV-2 cases’ fatality is linked to age.Significance StatementBronchial epithelia are the primary target for SARS-CoV-2 infections. Our work uses reconstituted bronchial epithelia from adults and children. We show that infection of adult epithelia with SARS-CoV-2 is rapid and results in the synchronized release of large clusters of infected cells and syncytia into the apical lumen contributing to the released infectious virus dose. Infection of children derived bronchial epithelia revealed an intrinsic resistance to infection and virus spread, probably as a result of a faster onset of interferon secretion. Thus, our data provide direct evidence for the epidemiological observation that children are less susceptible to SARS-CoV-2.
rPanglaoDB: an R package to download and merge labeled single-cell RNA-seq data from the PanglaoDB database
Authors: Osorio Daniel , Kuijjer Marieke L. , Cai James J. 
Published: May 2021

AbstractMotivationCharacterizing cells with rare molecular phenotypes is one of the promises of high throughput single-cell RNA sequencing (scRNA-seq) techniques. However, collecting enough cells with the desired molecular phenotype in a single experiment is challenging, requiring several samples preprocessing steps to filter and collect the desired cells experimentally before sequencing. Data integration of multiple public single-cell experiments stands as a solution for this problem, allowing the collection of enough cells exhibiting the desired molecular signatures. By increasing the sample size of the desired cell type, this approach enables a robust cell type transcriptome characterization.ResultsHere, we introduce rPanglaoDB, an R package to download and merge the uniformly processed and annotated scRNA-seq data provided by the PanglaoDB database. To show the potential of rPanglaoDB for collecting rare cell types by integrating multiple public datasets, we present a biological application collecting and characterizing a set of 157 fibrocytes. Fibrocytes are a rare monocyte-derived cell type, that exhibits both the inflammatory features of macrophages and the tissue remodeling properties of fibroblasts. This constitutes the first fibrocytes’ unbiased transcriptome profile report. We compared the transcriptomic profile of the fibrocytes against the fibroblasts collected from the same tissue samples and confirm their associated relationship with healing processes in tissue damage and infection through the activation of the prostaglandin biosynthesis and regulation pathway.Availability and ImplementationrPanglaoDB is implemented as an R package available through the CRAN repositories https://CRAN.R-project.org/package=rPanglaoDB.Contactdaniecos@uio.noSupplementary informationCode to replicate the case example and figure 1 is available at https://github.com/dosorio/rPanglaoDB
The Interpretation of Computational Model Parameters Depends on the Context
Authors: Eckstein Maria K. , Master Sarah L. , Xia Liyu , Dahl Ronald E. , Wilbrecht Linda , Collins Anne G.E. 
Published: May 2021

AbstractReinforcement Learning (RL) models have revolutionized the cognitive and brain sciences, promising to explain behavior from simple conditioning to complex problem solving, to shed light on developmental and individual differences, and to anchor cognitive processes in specific brain mechanisms. However, the RL literature increasingly reveals contradictory results, which might cast doubt on these claims. We hypothesized that many contradictions arise from two commonly-held assumptions about computational model parameters that are actually often invalid: That parameters generalize between contexts (e.g., tasks, models) and that they capture interpretable (i.e., unique, distinctive) neurocognitive processes. To test this, we asked 291 participants aged 8-30 years to complete three learning tasks in one experimental session, and fitted RL models to each. We found that some parameters (exploration / decision noise) showed significant generalization: they followed similar developmental trajectories, and were reciprocally predictive between tasks. However, generalization was significantly below ceiling. Furthermore, other parameters (learning rates, forgetting) did not show evidence of generalization, and sometimes even opposite developmental trajectories. Interpretability was low for all parameters. We conclude that the systematic study of context factors (e.g., reward stochasticity; task volatility) will be necessary to enhance the generalizability and interpretability of computational cognitive models.HighlightsComputational cognitive modeling often makes two implicit assumptions: 1) Model parameters generalize between studies and models. 2) Parameters are interpretable, i.e., neurally, cognitively, and/or mechanistically specific.We empirically investigate these assumptions in Reinforcement Learning (RL), using a large developmental dataset featuring three different learning tasks in a within-participant design.We find that no parameters generalize between tasks in terms of absolute parameter values. However, RL decision noise/exploration parameters generalize in terms of between-participant variation, showing similar age trajectories across tasks. Interpretability was low for all parameters, especially those related to learning and memory.Even for parameters that showed generalization, the degree of generalization was significantly lower than in an artificial sample with perfect generalization for most parameters, revealing a relative lack of generalization.These findings are in accordance with previous claims about the developmental trajectory of decision noise/exploration parameters, but suggest that claims about the development of learning rates or Forgetting might not be generalizable: these parameters are unlikely to capture the same neuro-cognitive processes across different tasks.We suggest ways forward to improve the generalizability and interpretability of model parameters, in particular by focusing more on task context.
The SARS-CoV-2 variants associated with infections in India, B.1.617, show enhanced spike cleavage by furin
Authors: Peacock Thomas P. , Sheppard Carol M. , Brown Jonathan C. , Goonawardane Niluka , Zhou Jie , Whiteley Max ,   PHE Virology Consortium, de Silva Thushan I. , Barclay Wendy S. 
Published: May 2021

AbstractThe spike (S) glycoprotein of the SARS-CoV-2 virus that emerged in 2019 contained a suboptimal furin cleavage site at the S1/S2 junction with the sequence 681PRRAR/S686. This cleavage site is required for efficient airway replication, transmission, and pathogenicity of the virus. The B.1.617 lineage has recently emerged in India, coinciding with substantial disease burden across the country. Early evidence suggests that B.1.617.2 (a sublineage of B.1.617) is more highly transmissible than contemporary lineages. B.1.617 and its sublineages contain a constellation of S mutations including the substitution P681R predicted to further optimise this furin cleavage site. We provide experimental evidence that virus of the B.1.617 lineage has enhanced S cleavage, that enhanced processing of an expressed B.1.617 S protein in cells is due to P681R, and that this mutation enables more efficient cleavage of a peptide mimetic of the B.1.617 S1/S2 cleavage site by recombinant furin. Together, these data demonstrate viruses in this emerging lineage have enhanced S cleavage by furin which we hypothesise could be enhancing transmissibility and pathogenicity.
Group II truncated haemoglobin YjbI prevents reactive oxygen species-induced protein aggregation in Bacillus subtilis
Authors: Imai Takeshi , Tobe Ryuta , Honda Koji , Tanaka Mai , Kawamoto Jun , Mihara Hisaaki 
Published: May 2021

AbstractOxidative stress–mediated formation of protein hydroperoxides can induce irreversible fragmentation of the peptide backbone and accumulation of cross-linked protein aggregates, leading to cellular toxicity, dysfunction, and death. However, how bacteria protect themselves from damages caused by protein hydroperoxidisation is unknown. Here we show that YjbI, a group II truncated haemoglobin from Bacillus subtilis, prevents oxidative aggregation of cell-surface proteins by its biologically unprecedented protein hydroperoxide peroxidase-like activity, which removes hydroperoxide groups from oxidised proteins. Disruption of the yjbI gene in B. subtilis lowered biofilm water repellence and the mechanical stiffness of the cell surface, which associated with the cross-linked aggregation of the biofilm matrix protein TasA. YjbI was localised to the cell surface, and the sensitivity of planktonically grown cells to generators of reactive oxygen species was significantly increased upon yjbI disruption, suggesting that YjbI pleiotropically protects labile cell-surface proteins from oxidative damage. YjbI removed hydroperoxide residues from a model oxidised protein substrate, bovine serum albumin, and prevented its oxidative aggregation in vitro. These findings provide new insights into the role of truncated haemoglobin and the importance of hydroperoxide removal from proteins in the survival of aerobic bacteria.
Global analysis of the zinc homeostasis network in Pseudomonas aeruginosa and its gene expression dynamics
Authors: Ducret Verena , Abdou Melina , Milho Catarina Goncalves , Leoni Sara , Martin--Pelaud Oriane , Sandoz Antoine , Campos Inés Segovia , Tercier-Waeber Mary-Lou , Valentini Martina , Perron Karl 
Published: May 2021

AbstractZinc is one of the most important trace elements for life and its deficiency, like its excess, can be fatal. In the bacterial opportunistic pathogen Pseudomonas aeruginosa, Zn homeostasis is not only required for survival, but also for virulence and antibiotic resistance. Thus, the bacterium possesses multiple Zn import/export/storage systems. In this work, we determine the expression dynamics of the entire P. aeruginosa Zn homeostasis network at both transcript and protein levels. Precisely, we followed the switch from a Zn-deficient environment, mimicking the initial immune strategy to counteract bacterial infections, to a Zn-rich environment, representing the phagocyte metal boost used to eliminate an engulfed pathogen. Thanks to the use of the NanoString technology, we timed the global silencing of Zn import systems and the orchestrated induction of Zn export systems. We show that the induction of Zn export systems is hierarchically organized as a function of their impact on Zn homeostasis. Moreover, we identify PA2807 as a novel Zn resistance component in P. aeruginosa and highlight new regulatory links among Zn-homeostasis systems. Altogether, this work unveils a sophisticated and adaptive homeostasis network, which complexity is key in determining a pathogen spread in the environment and during host-colonization.
Rapid evolution of bacterial AB5 toxin B subunits independent of A subunits: sialic acid binding preferences correlate with host range and toxicity
Authors: Khan Naazneen , Sasmal Aniruddha , Khedri Zahra , Secrest Patrick , Verhagen Andrea , Srivastava Saurabh , Varki Nissi , Chen Xi , Yu Hai , Beddoe Travis , Paton Adrienne W. , Paton James C. , Varki Ajit 
Published: May 2021

AbstractCytotoxic A subunits of bacterial AB5 toxins enter the cytosol following B subunit binding to host cell glycans. We report that A subunit phylogeny evolves independently of B subunits and suggest a future B subunit nomenclature based on species name. Phylogenetic analysis of B subunits that bind sialic acids (Sias) with homologous molecules in databases also show poor correlation with phylogeny. These data indicate ongoing lateral gene transfers between species, with mixing of A and B subunits. Some B subunits are not even associated with A subunits e.g., YpeB of Yersinia pestis, the etiologic agent of plague epidemics. Plague cannot be eradicated because of Y. pestis’ adaptability to numerous hosts. YpeB shares 58% identity/79% similarity with the homo-pentameric B subunit of E. coli Subtilase cytotoxin, and 48% identity/68% similarity with the B subunit of S. Typhi typhoid toxin. We previously showed selective binding of B5 pentamers to a sialoglycan microarray, with Sia preferences corresponding to hosts e.g., N-acetylneuraminic acid (Neu5Ac; prominent in humans) or N-glycolylneuraminic acid (Neu5Gc; prominent in ruminant mammals and rodents). Consistent with much broader host range of Y. pestis, YpeB binds all mammalian sialic acid types, except for 4-O-acetylated ones. Notably, YpeB alone causes dose-dependent cytotoxicity, abolished by a mutation (Y77F) eliminating Sia recognition, suggesting cell proliferation and death via lectin-like cross-linking of cell surface sialoglycoconjugates. These findings help explain the host range of Y. pestis and could be important for pathogenesis. Overall, our data indicate ongoing rapid evolution of both host Sias and pathogen toxin-binding properties.
GIGANTEA gene expression influence leaf senescence in Populus in two different ways
Authors: Fataftah Nazeer , Bag Pushan , André Domenique , Lihavainen Jenna , Zhang Bo , Ingvarsson Pär K , Nilsson Ove , Jansson Stefan 
Published: May 2021

AbstractGIGANTEA (GI) genes have a central role in plant development and influence several processes such as light signaling, circadian rhythm and abiotic stress tolerance. Hybrid aspen T89 (Populus tremula x tremuloides) trees with low GI expression through RNAi have a severely compromised growth. In order to study the effect of reduced GI expression on leaf traits with special emphasis on leaf senescence, we grafted GI-RNAi scions onto wild type (WT) rootstocks and managed to restore scions’ growth. The RNAi line had distorted leaf shape and reduced photosynthesis, probably caused by modulating phloem or stomatal function, increased starch accumulation, higher carbon-to-nitrogen (C/N) ratio and a reduced capacity to withstand moderate light stress. GI-RNAi also induced senescence under long day (LD) and moderate light conditions. Furthermore, the GI-RNAi lines were affected in their capacity to respond to “autumn environmental cues” inducing senescence, a type of leaf senescence with characteristics different from senescence induced directly by stress under LD conditions. Whereas Overexpression of GI delayed senescence. The two different effects on leaf senescence were not affected by the expression of FT (Flowering locus T), were “local” – they followed the genotype of the branch independent on the position in the tree – and trees with modified gene expression grown in the field were affected in a similar way as under controlled conditions. Taken together, GI plays a central role to sense the environmental changes during autumn and determine the appropriate timing for leaf senescence in Populus.One sentence summaryLeaf senescence is a complex process that is not well understood, but this paper shows that changing the expression of one gene could influence leaf senescence in Populus trees in two separate ways.