bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and dynamics of human cardiac fibroblast nanotubes
Authors: Schmid-Herbstritt S.C. , Stief G. , Greiner J. , Felekary A. , Madl J. , Zeidler V. , Heer J. , Iaconianni P. , Koch M. , Kollmar K. , Walz C. , Nübling S. , Kok T. , Pronto J.R. , Kutschka I. , Voigt N. , Morgan G. , Dienert J. , Brox T. , Briquez P. , Peyronnet R. , Rohrbach A. , Kohl P. , Rog-Zielinska E.A. 
Published: November 2023

AbstractEfficient and dynamic interactions between cardiac fibroblasts and their environment are essential for the maintenance of tissue homeostasis in healthy hearts and play an important role during pathological remodelling. Here, we investigate a relatively obscure mechanism through which human atrial fibroblasts communicate with each other, with other cells, and with the extracellular matrix (ECM) – nanotubes (NT). We investigated NT structure and dynamics in primary right atrial fibroblasts isolated from patients in sinus rhythm (SR) and atrial fibrillation (AF), in an immortalised human atrial fibroblasts cell line, and in intact human tissue, using a wide range of imaging approaches (including confocal microscopy, label-free reflection microscopy, rotating coherent scattering microscopy, and cryo-electron tomography). We show that fibroblasts maintain continuous NT activityin vitro, with numerous protrusions constantly probing the surrounding environment. NT structure and activity change during AF and following pharmacological (transforming growth factor-β, latrunculin B) and environmental (hypoxia) interventions. We also show that cardiac fibroblast NT mediate intercellular organelle exchange and dynamically interact with ECM. Finally, we present evidence for the presence of fibroblast-borne NT in human atrial tissue. Our results advance our understanding of how cardiac fibroblasts interact with their environment. NT are versatile structures capable of both sensory and actuating functions, and offer a dynamic and rapid communication conduit that facilitates cell–cell and cell–extracellular matrix interactions.
Performance of Chrysanthemum Cultivars under Agro-climatic condition of Chhattisgarh plains
Authors: Bhoi Madhusmita , Tirkey Tarsiyus 
Published: November 2023

ABSTRACTChrysanthemum is the second largest flower after rose in the global ornamental plants market; It is third in terms of cut flower and ranks fifth in global floriculture trading. Therefore, floricultural study of chrysanthemum has gained widespread attention recently. As the state of Chhattisgarh is rising as a floral hub, we are propelled to determine suitable cultivars of chrysanthemum for different characters in Chhattisgarh plains. To this end, we conducted an experiment based on Randomized Block Design (under field condition) during the year 2016-2017, with seven cultivars of Chrysanthemum namely Pusa Sona, Pusa Arunodaya, Pusa Kesari, Pusa Chitraksha, Pusa Aditya, Mother Teresa, and White Prolific. Our results indicate that Pusa Sona exhibits the early bud appearance (32.80 days), early flowering (60.27 days), maximum number of flowers per plant (137.80), and maximum number of branches per plant (19.73). Further, maximum plant height (49.47 cm) and plant spread (32.63 cm) were observed in Pusa Chitraksha. While Pusa Kesari recorded maximum flower diameter (7.00 cm) and maximum weight of flowers per plant (177.50 g), the maximum flowering duration (59.40 days) was noted under Pusa Aditya. We are certain that these novel findings would help floriculturists’ decision making significantly regarding chrysanthemum plantation.
Enhanced detection of RNA modifications and mappability with high-accuracy nanopore RNA basecalling models
Authors: Diensthuber Gregor , Pryszcz Leszek , Llovera Laia , Lucas Morghan C , Delgado-Tejedor Anna , Cruciani Sonia , Roignant Jean-Yves , Begik Oguzhan , Novoa Eva Maria 
Published: November 2023

ABSTRACTIn recent years, nanopore direct RNA sequencing (DRS) has established itself as a valuable tool for studying the epitranscriptome, due to its ability to detect multiple modifications within the same full-length native RNA molecules. While RNA modifications can be identified in the form of systematic basecalling ‘errors’ in DRS datasets,N6-methyladenosine (m6A) modifications produce relatively low ‘errors’ compared to other RNA modifications, limiting the applicability of this approach to m6A sites that are modified at high stoichiometries. Here, we demonstrate that the use of alternative RNA basecalling models, trained with fully unmodified sequences, increases the ‘error’ signal of m6A, leading to enhanced detection and improved sensitivity even at low stoichiometries. Moreover, we find that high-accuracy alternative RNA basecalling models can show up to 97% median basecalling accuracy, outperforming currently available RNA basecalling models, which show 91% median basecalling accuracy. Notably, the use of high-accuracy basecalling models is accompanied by a significant increase in the number of mapped reads –especially in shorter RNA fractions– and increased basecalling error signatures at pseudouridine (Ψ) and N1-methylpseudouridine (m1Ψ) modified sites. Overall, our work demonstrates that alternative RNA basecalling models can be used to improve the detection of RNA modifications, read mappability and basecalling accuracy in nanopore DRS datasets.
Eco-evolutionary dynamics of partially migratory metapopulations in spatially and seasonally varying environments
Authors: Haaland Thomas R. , Payo-Payo Ana , Acker Paul , Fortuna Rita , Burthe Sarah J. , Ratikainen Irja I. , Daunt Francis , Reid Jane M. 
Published: November 2023

AbstractPredicting population responses to environmental changes requires understanding interactions among environmentally induced phenotypic variation, selection, demography and genetic variation, and thereby predicting eco-evolutionary dynamics emerging across diverse temporal and spatial scales. Partially migratory metapopulations (PMMPs), featuring seasonal coexistence of resident and migrant individuals across multiple spatially distinct subpopulations, have clear potential for complex spatio-seasonal eco-evolutionary dynamics through impacts of selection on migration on spatial population dynamics, and feedbacks resulting from ongoing micro-evolution. However, the key genetic and environmental conditions that maintain migratory polymorphisms, and eco-evolutionary dynamics of PMMPs under stochastic environmental variation and strong seasonal perturbations, have not yet been resolved. Accordingly, we present a general individual-based model that tracks eco-evolutionary dynamics in PMMPs inhabiting spatially structured, seasonally varying landscapes, with migration formulated as a quantitative genetic threshold trait. Our simulations show that such genetic and landscape structures, which commonly occur in nature, can readily produce a variety of stable partially migratory systems given diverse regimes of spatio-seasonal environmental variation. Typically, partial migration is maintained whenever sites differ in non-breeding season suitability resulting from variation in density-dependence, causing ‘ideal free’ non-breeding distributions where residents and migrants occur with frequencies that generate similar survival probabilities. Yet, stable partial migration can also arise without any fixed differences in non-breeding season density-dependence among sites, and even without density-dependence at all, through risk-spreading given sufficiently large stochastic environmental fluctuations among sites and years. Finally, we show that local non-breeding season mortality events, as could result from extreme climatic events, can generate eco-evolutionary dynamics that ripple out to affect breeding and non-breeding season space use of subpopulations throughout the PMMP, on both short and longer timeframes. Such effects result from spatially divergent selection on both the occurrence and destinations of migration. Our model thus shows how facultative seasonal migration can act as a key mediator of eco-evolutionary dynamics in spatially and seasonally structured environments, providing key steps towards predicting responses of natural partially migratory populations to ongoing changes in spatio-seasonal patterns of environmental variation.
High-yield enzymatic synthesis of mono– and trifluorinated alanine enantiomers
Authors: Nieto-Dominguez Manuel , Sako Aboubakar , Enemark-Rasmussen Kasper , Gotfredsen Charlotte Held , Rago Daniela , Nikel Pablo I. 
Published: November 2023

ABSTRACTFluorinated amino acids are a promising entry point for incorporating new-to-Nature chemistries in biological systems. Hence, novel methods are needed for the selective synthesis of these building blocks. In this study, we focused on the enzymatic synthesis of fluorinated alanine enantiomers. To this end, the alanine dehydrogenase fromVibrio proteolyticusand the diaminopimelate dehydrogenase fromSymbiobacterium thermophilumwere applied to thein vitroproduction of (R)-3-fluoroalanine and (S)-3-fluoroalanine, respectively, using 3-fluoropyruvate as the substrate. Additionally, an alanine racemase fromStreptomyces lavendulae, originally selected for setting an alternative enzymatic cascade leading to the production of these non-canonical amino acids, had an unprecedented catalytic efficiency in the β-elimination of fluorine from the monosubstituted fluoroalanine. Thein vitroenzymatic cascade based on the dehydrogenases ofV.proteolyticusandS.thermophilumincluded a cofactor recycling system, whereby a formate dehydrogenase fromPseudomonassp. 101 (either native or engineered) coupled formate oxidation to NAD(P)H formation. Under these conditions, the reaction yields for (R)-3-fluoroalanine and (S)-3-fluoroalanine reached >85% on the fluorinated substrate and proceeded with complete enantiomeric excess. Moreover, the selected dehydrogenases were also able to catalyze the conversion of trifluoropyruvate into trifluorinated alanine, as a first-case example of biocatalysis with amino acids carrying a trifluoromethyl group.
Glutathione accelerates the cell cycle and cellular reprogramming in plant regeneration
Authors: Lee Laura R , Guillotin Bruno , Rahni Ramin , Hutchison Chanel , Desvoyes Bénédicte , Gutierrez Crisanto , Birnbaum Kenneth D 
Published: November 2023

SummaryThe plasticity of plant cells underlies their wide capacity to regenerate, with increasing evidence in plants and animals implicating cell cycle dynamics in cellular reprogramming. To investigate the cell cycle during cellular reprogramming, we developed a comprehensive set of cell cycle phase markers in the Arabidopsis root. Using single-cell RNA-seq profiles and live imaging during regeneration, we found that a subset of cells near an ablation injury dramatically increases division rate by truncating G1. Cells in G1 undergo a transient nuclear peak of glutathione (GSH) prior to coordinated entry into S phase followed by rapid divisions and cellular reprogramming. A symplastic block of the ground tissue impairs regeneration, which is rescued by exogenous GSH. We propose a model in which GSH from the outer tissues is released upon injury licensing an exit from G1 near the wound to induce rapid cell division and reprogramming.
Human mutations in high-confidence Tourette disorder genes affect sensorimotor behavior, reward learning, and striatal dopamine in mice
Authors: Nasello Cara , Poppi Lauren A. , Wu Junbing , Kowalski Tess F. , Thackray Joshua K. , Wang Riley , Persaud Angelina , Mahboob Mariam , Lin Sherry , Spaseska Rodna , Johnson C.K. , Gordon Derek , Tissir Fadel , Heiman Gary A. , Tischfield Jay A. , Bocarsly Miriam , Tischfield Max A. 
Published: November 2023

AbstractTourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous to humande novovariants in two high-confidence Tourette genes,CELSR3andWWC1. Mice with human mutations inCelsr3andWwc1exhibit cognitive and/or sensorimotor behavioral phenotypes consistent with TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition, occur in both male and femaleCelsr3TD models.Wwc1mice show reduced prepulse inhibition only in females. Repetitive motor behaviors, common toCelsr3mice and more pronounced in females, include vertical rearing and grooming. Sensorimotor gating deficits and rearing are attenuated by aripiprazole, a partial agonist at dopamine type II receptors. Unsupervised machine learning reveals numerous changes to spontaneous motor behavior and less predictable patterns of movement. Continuous fixed-ratio reinforcement showsCelsr3TD mice have enhanced motor responding and reward learning. Electrically evoked striatal dopamine release, tested in one model, is greater. Brain development is otherwise grossly normal without signs of striatal interneuron loss. Altogether, mice expressing human mutations in high-confidence TD genes exhibit face and predictive validity. Reduced prepulse inhibition and repetitive motor behaviors are core behavioral phenotypes and are responsive to aripiprazole. Enhanced reward learning and motor responding occurs alongside greater evoked dopamine release. Phenotypes can also vary by sex and show stronger affection in females, an unexpected finding considering males are more frequently affected in TD.Significance StatementWe generated mouse models that express mutations in high-confidence genes linked to Tourette disorder (TD). These models show sensorimotor and cognitive behavioral phenotypes resembling TD-like behaviors. Sensorimotor gating deficits and repetitive motor behaviors are attenuated by drugs that act on dopamine. Reward learning and striatal dopamine is enhanced. Brain development is grossly normal, including cortical layering and patterning of major axon tracts. Further, no signs of striatal interneuron loss are detected. Interestingly, behavioral phenotypes in affected females can be more pronounced than in males, despite male sex bias in the diagnosis of TD. These novel mouse models with construct, face, and predictive validity provide a new resource to study neural substrates that cause tics and related behavioral phenotypes in TD.
Dispersal of a dominant competitor can drive multispecies coexistence in biofilms
Authors: Holt Jacob D. , Schultz Daniel , Nadell Carey D. 
Published: November 2023

AbstractDespite competition for both space and nutrients, bacterial species often coexist within structured, surface-attached communities termed biofilms. While these communities play important, widespread roles in ecosystems and are agents of human infection, understanding how multiple bacterial species assemble to form these communities and what physical processes underpin the composition of multispecies biofilms remains an active area of research. Using a model three-species community composed ofP. aeruginosa,E. coli, andE. faecalis, we show with cellular scale resolution that biased dispersal of the dominant community member,P. aeruginosa, prevents competitive exclusion from occurring, leading to coexistence of the three species. AP. aeruginosa bqsSdeletion mutant no longer undergoes periodic mass dispersal, leading to local competitive exclusion ofE. coli. Introducing periodic, asymmetric dispersal behavior into minimal models parameterized by only maximal growth rate and local density supports the intuition that biased dispersal of an otherwise dominant competitor can permit coexistence generally. Colonization experiments show that WTP. aeruginosais superior at colonizing new areas in comparison toΔbqsS P. aeruginosa, but at the cost of decreased local competitive ability againstE. coliandE. faecalis. Overall, our experiments document how one species’ modulation of a competition-dispersal-colonization trade-off can go on to influence the stability of multispecies coexistence in spatially structured ecosystems.
Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning
Authors: Lei Ruipeng , Qing Enya , Odle Abby , Yuan Meng , Tan Timothy J.C. , So Natalie , Ouyang Wenhao O. , Wilson Ian A. , Gallagher Tom , Perlman Stanley , Wu Nicholas C. , Wong Lok-Yin Roy 
Published: November 2023

ABSTRACTThe fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane fusion during virus entry and is part of a broadly neutralizing epitope. However, sequence determinants at the fusion peptide and its adjacent regions for pathogenicity and antigenicity remain elusive. In this study, we performed a series of deep mutational scanning (DMS) experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 in different cell lines and in the presence of broadly neutralizing antibodies. We identified mutations at residue 813 of the spike protein that reduced TMPRSS2-mediated entry with decreased virulence. In addition, we showed that an F823Y mutation, present in bat betacoronavirus HKU9 spike protein, confers resistance to broadly neutralizing antibodies. Our findings provide mechanistic insights into SARS-CoV-2 pathogenicity and also highlight a potential challenge in developing broadly protective S2-based coronavirus vaccines.
copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling
Authors: Kovaleva Vasilisa A. , Pattinson David J. , Barton Carl , Chapin Sarah R. , Minervina Anastasia A. , Richards Katherine A. , Sant Andrea J. , Thomas Paul G. , Pogorelyy Mikhail V. , Meyer Hannah V. 
Published: November 2023

AbstractT cell receptor (TCR) repertoire diversity enables the orchestration of antigen-specific immune responses against the vast space of possible pathogens. Identifying TCR/antigen binding pairs from the large TCR repertoire and antigen space is crucial for biomedical research. Here, we introducecopepodTCR, an open-access tool for the design and interpretation of high-throughput experimental assays to determine TCR specificity.copepodTCRimplements a combinatorial peptide pooling scheme for efficient experimental testing of T cell responses against large overlapping peptide libraries, useful for “deorphaning” TCRs of unknown specificity. The scheme detects experimental errors and, coupled with a hierarchical Bayesian model for unbiased results interpretation, identifies the response-eliciting peptide for a TCR of interest out of hundreds of peptides tested using a simple experimental set-up. We experimentally validated our approach on a library of 253 overlapping peptides covering the SARS-CoV-2 spike protein. We provide experimental guides for efficient design of larger screens covering thousands of peptides which will be crucial for the identification of antigen-specific T cells and their targets from limited clinical material.
RankCompV3: a differential expression analysis algorithm based on relative expression orderings and applications in single-cell RNA transcriptomics
Authors: Yan Jing , Zeng Qiuhong , Wang Xianlong 
Published: November 2023

AbstractEffective identification of differentially expressed genes (DEGs) has been challenging for single-cell RNA sequencing (scRNA-seq) profiles. Many existing algorithms have high false positive rates (FPRs) and often fail to identify weak biological signals. Here, we present a novel method for identifying DEGs in scRNA-seq data called RankCompV3. It is based on the comparison of relative expression orderings (REOs) of gene pairs which are determined by comparing the expression levels of a pair of genes in a set of single-cell profiles. The numbers of genes with consistently higher or lower expression levels than the gene of interest are counted in two groups in comparison, respectively, and the result is tabulated in a 3×3 contingency table which is tested by McCullagh’s method to determine if the gene is dysregulated. In both simulated and real scRNA-seq data, RankCompV3 tightly controlled the FPR and demonstrated high accuracy, outperforming 11 other common single-cell DEG detection algorithms. Analysis with either regular single-cell or synthetic pseudo-bulk profiles produced highly concordant DEGs with ground-truth. In addition, RankCompV3 demonstrates higher sensitivity to weak biological signals than other methods. The algorithm was implemented using Julia and can be called in R. The source code is available athttps://github.com/pathint/RankCompV3.jl.
Origin and evolution of the bread wheat D genome
Authors: Cavalet-Giorsa Emile , González-Muñoz Andrea , Athiyannan Naveenkumar , Holden Samuel , Salhi Adil , Gardener Catherine , Quiroz-Chávez Jesús , Rustamova Samira M. , Elkot Ahmed F. , Patpour Mehran , Rasheed Awais , Mao Long , Lagudah Evans S. , Periyannan Sambasivam K. , Sharon Amir , Himmelbach Axel , Reif Jochen C. , Knauft Manuela , Mascher Martin , Stein Nils , Chayut Noam , Ghosh Sreya , Perovic Dragan , Putra Alexander , Perera Ana B. , Hu Chia-Yi , Yu Guotai , Ahmed Hanin Ibrahim , Laquai Konstanze D. , Rivera Luis F. , Chen Renjie , Wang Yajun , Gao Xin , Liu Sanzhen , Raupp W. John , Olson Eric L. , Lee Jong-Yeol , Chhuneja Parveen , Kaur Satinder , Zhang Peng , Park Robert F. , Ding Yi , Liu Deng-Cai , Li Wanlong , Nasyrova Firuza Y. , Dvorak Jan , Abbasi Mehrdad , Li Meng , Kumar Naveen , Meyer Wilku B. , Boshoff Willem H. P. , Steffenson Brian J. , Matny Oadi , Sharma Parva K. , Tiwari Vijay K. , Grewal Surbhi , Pozniak Curtis , Chawla Harmeet Singh , Ens Jennifer , Dunning Luke T. , Kolmer James A. , Lazo Gerard R. , Xu Steven , Gu Yongqiang , Xu Xianyang , Uauy Cristobal , Abrouk Michael , Bougouffa Salim , Brar Gurcharn S. , Wulff Brande B. H. , Krattinger Simon G. 
Published: November 2023

AbstractBread wheat (Triticum aestivum) is a globally dominant crop and major source of calories and proteins for the human diet. Compared to its wild ancestors, modern bread wheat shows lower genetic diversity caused by polyploidisation, domestication, and breeding bottlenecks1,2. Wild wheat relatives represent genetic reservoirs, harbouring diversity and beneficial alleles that have not been incorporated into bread wheat. Here, we establish and analyse pangenome resources for Tausch’s goatgrass,Aegilops tauschii, the donor of the bread wheat D genome. This new pangenome facilitated the cloning of a disease resistance gene and haplotype analysis across a complex disease resistance locus, allowing us to discern alleles from paralogous gene copies. We also reveal the complex genetic composition and history of the bread wheat D genome, involving previously unreported contributions from genetically and geographically discreteAe. tauschiisubpopulations. Together, our results reveal the complex history of the bread wheat D genome and demonstrate the potential of wild relatives in crop improvement.