bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guided by touch: Tactile Cues in Hand Movement Control
Authors: Vlachou Maria Evangelia , Legros Juliette , Sellin Cécile , Paleressompoulle Dany , Massi Francesco , Simoneau Martin , Mouchnino Laurence , Blouin Jean 
Published: July 2024

AbstractTraditionally, touch is associated with exteroception and is rarely considered a relevant sensory cue for controlling movements in space, unlike vision. We developed a technique to isolate and evaluate tactile involvement in controlling sliding finger movements over a surface. Young adults traced a 2D shape with their index finger under direct or mirror-reversed visual feedback to create a conflict between visual and somatosensory inputs. In this context, increased reliance on somatosensory input compromises movement accuracy. Based on the hypothesis that tactile cues contribute to guiding hand movements, we predicted poorer performance when the participants traced with their bare finger compared to when their tactile sensation was dampened using a smooth finger splint. The results supported this prediction. EEG source analyses revealed smaller current in the presumed somatosensory cortex during sensory conflict, but only when the finger directly touched the surface. This finding suggests the gating of task-irrelevant somatosensory inputs. Together, our results emphasize touch’s involvement in movement control, challenging the notion that vision predominantly governs goal-directed hand or finger movements.
Partial redundancy buffers deleterious effects of mutatingDNA methyltransferase 1-1(MET1-1) in polyploid wheat
Authors: Burrows Samuel , Dorussen Delfi , Crudgington Joseph , Di Santolo Giorgia , Simmonds James , Catoni Marco , Borrill Philippa 
Published: July 2024

AbstractDNA methylation is conserved across biological kingdoms, playing important roles in gene expression, transposable element silencing and genome stability. Altering DNA methylation could generate additional phenotypic variation for crop breeding, however the lethality of epigenetic mutants in crop species has hindered its investigation. Here, we exploit partial redundancy between homoeologs in polyploid wheat to generate viable mutants in the DNAmethyltransferase 1-1(MET1-1) gene with altered methylation profiles. In bothTriticum turgidum(tetraploid wheat) andTriticum aestivum(hexaploid wheat) we identified clear segregation distortions of higher-order mutants (5/6 and 6/6 mutantmet1-1copies in hexaploid and 3/4 and 4/4 copies in tetraploid) when genotyping segregating seeds and seedlings, which we attribute to reduced transmission of null mutant gametes. We found that the reduced transmission occurred from both the maternal and paternal gametes, however, we did not detect any deleterious effects on pollen development. The loss of four or more functional copies ofMET1-1results in decreased CG methylation in hexaploid wheat. Changes to gene expression increase stepwise with the number of mutant alleles suggesting a dosage dependent effect. Finally, we identify heritable changes to flowering and awn phenotypes which segregate independently ofMET1-1. Together our results demonstrate that polyploidy can be leveraged to generate quantitative changes to CG methylation without the lethal consequences observed in other crops, opening the potential to exploit novel epialleles in plant breeding.
Multiscale Molecular Modelling of Chromatin with MultiMM: From Nucleosomes to the Whole Genome
Authors: Korsak Sevastianos , Banecki Krzysztof , Plewczynski Dariusz 
Published: July 2024

AbstractMotivationWe present a user-friendly 3D chromatin simulation model based on OpenMM, addressing the challenges posed by existing models with use-specific implementations. Our approach employs a multi-scale energy minimization strategy, capturing chromatin’s hierarchical structure. Initiating with a Hilbert curve-based structure, users can input files specifying nucleosome positioning, loops, compartments, or subcompartments.ResultsThe model utilizes an energy minimization approach with a large choice of numerical integrators, providing the entire genome’s structure within minutes. Output files include the generated structures for each chromosome, offering a versatile and accessible tool for chromatin simulation in bioinformatics studies. Furthermore, MultiMM is capable of producing nucleosomeresolution structures by making simplistic geometric assumptions about the structure and the density of nucleosomes on the DNA.Code availabilityOpen-source software and the manual are freely available onhttps://github.com/SFGLab/MultiMM.
Asynchronous mouse embryo polarization leads to heterogeneity in cell fate specification
Authors: Lamba Adiyant , Zhu Meng , Meglicki Maciej , Czukiewska Sylwia , Balasubramaniam Lakshmi , Hadas Ron , Weishaupt Nina , Patel Ekta M. , Kavanagh Yu Hua , Wang Ran , Jing Naihe , Zernicka-Goetz Magdalena 
Published: July 2024

AbstractThe first lineage allocation in mouse and human embryos separates the inner cell mass (ICM) from the outer trophectoderm (TE). This symmetry breaking event is executed through polarization of cells at the 8-cell stage and subsequent asymmetric divisions, generating polar (TE) and apolar (ICM) cells. Here, we show that embryo polarization is unexpectedly asynchronous. Cells polarizing at the early and late 8-cell stage have distinct molecular and morphological properties that direct their following lineage specification, with early polarizing cells being biased towards producing the TE lineage. More recent studies have also implicated heterogeneities between cells prior to the 8-cell stage in the first lineage allocation: cells exhibiting reduced methyltransferase CARM1 activity at the 4-cell stage are predisposed towards the TE fate. Here, we demonstrate that reduced CARM1 activity and upregulation of its substrate BAF155 promote early polarization and TE specification. These findings provide a link between asymmetries at the 4-cell stage and polarization at the 8-cell stage, mechanisms of the first lineage allocation that had been considered separate.
DOCK8 regulates a mechanosensitive actin redistribution that maintains immune cell cohesion and protects the nucleus during migration
Authors: Shen Connie , Postat Jérémy , Cerf Aysha , Merino Mauricio , Bhagrath Aanya , Patel Dhanesh , Luo Vincent , Abu-Thuraia Afnan , Schneider Caitlin , Sharma Abhinav , Suh Woong-Kyung , Ehrlicher Allen , Côté Jean-François , Mandl Judith N. 
Published: July 2024

AbstractImmune cells navigate through complex 3-dimensional tissue architectures, utilizing an amoeboid mode of migration, characterized by extensive cellular deformation, low adhesion, and high cell velocities. In the absence of expression ofDedicator of Cytokinesis 8 (Dock8), a gene identified with loss-of-function mutations in immunodeficiency, cells become entangled during migration through dense, confined environments and consequently undergo catastrophic cell rupturing, while migration on 2D surfaces remains entirely intact. Here we investigated the specific cytoskeletal defect ofDock8-deficient activated T cells, showing that even prior to entanglement they display a striking difference in F-actin distribution compared to wild type (WT) cells. We describe a central pool of F-actin in WT murine and human T cells which is absent inDock8KO T cells, and determine that the relocalization of F-actin is a mechanoresponsive circuit, emerging only when cells are very confined. Our works shows that the central actin pool is nucleo-protective, reducing nuclear deformation and DNA damage during confined migration. We identify the Hippo-pathway kinase Mst1 as a co-mediator of this mechanosensitive pathway in conjunction with Dock8, allowing for cell cohesion and survival during migration through complex environments.
Successful retrieval is its own reward
Authors: Smith Devyn E. , Long Nicole M. 
Published: July 2024

AbstractThe ability to successfully remember past events is critical to our daily lives, yet the neural mechanisms underlying the motivation to retrieve is unclear. Although reward-system activity and feedback-related signals have been observed during memory retrieval, whether this signal reflects intrinsic reward or goal-attainment is unknown. Adjudicating between these two alternatives is crucial for understanding how individuals are motivated to engage in retrieval and how retrieval supports later remembering. To test these two accounts, we conducted between-subjects recognition memory tasks on human participants undergoing scalp electroencephalography and varied test-phase goals (recognize old vs. detect new items). We used an independently validated feedback classifier to measure positive feedback evidence. We find positive feedback following successful retrieval regardless of task goals. Together, these results suggest that successful retrieval is intrinsically rewarding. Such a feedback signal may promote future retrieval attempts as well as bolster later memory for the successfully retrieved events.
Epileptiform activity and seizure risk follow long-term non-linear attractor dynamics
Authors: Rosch Richard E , Scheid Brittany , Davis Kathryn A , Litt Brian , Ashourvan Arian 
Published: July 2024

AbstractMany biological systems display circadian and slow multi-day rhythms, such as hormonal and cardiac cycles. In patients with epilepsy, these cycles also manifest as slow cyclical fluctuations in seizure propensity. However, such fluctuations in symptoms are consequences of the complex interactions between the underlying physiological, pathophysiological, and external causes. Therefore, identifying an accurate model of the underlying system that governs the multi-day rhythms allows for a more reliable seizure risk forecast and targeted interventions. To achieve this goal, we adopt the Hankel alternative view of Koopman (HAVOK) analysis to approximate a linear representation of nonlinear seizure propensity dynamics. The HAVOK framework leverages Koopman theory and delay-embedding to decompose chaotic dynamics into a linear system of leading delay-embedded coordinates driven by the low-energy coordinate (i.e., forcing). Our findings reveal the topology of attractors underlying multi-day seizure cycles, showing that seizures tend to occur in regions of the manifold with strongly nonlinear dynamics. Moreover, we demonstrate that the identified system driven by forcings with short periods up to a few days accurately predicts patients’ slower multi-day rhythms, which improves seizure risk forecasting.
Phylogenomics resolves the relationship and the evolutionary history of planthoppers (Insecta: Hemiptera: Fulgoromorpha)
Authors: Deng Junchen , Stroiński Adam , Szwedo Jacek , Ghanavi Hamid Reza , Yapar Etka , Franco Diego Castillo , Prus-Frankowska Monika , Michalik Anna , Wahlberg Niklas , Łukasik Piotr 
Published: July 2024

AbstractPlanthoppers (Hemiptera: Fulgoromorpha) are a species-rich and globally distributed insect clade with high economic, ecological, and evolutionary importance. However, the relationships among planthopper lineages and families remain unclear. Previous efforts based on inconsistent morphological traits, a few genes, or limited sampling often resulted in conflicting tree topologies. Here, we used genome-level data to assemble 1164 nuclear single-copy genes and 13 mitochondrial protein-coding genes for 149 planthopper species representing 19 out of 21 extant families. Additional markers were added from published mitogenomes, expanding our sampling to 285 species. These markers were used for Maximum Likelihood-based tree inference and dating analyses. The newly inferred phylogenies validated well-accepted relationships and recovered novel placements. Taxonomic conclusions include the establishment of a new family Borysthenidaestat. rev.within Delphacoidea and a new superfamily Meenoploideasuperfam. nov.including redefined Kinnaridaestat. rev.and Meenoplidaestat. rev., the confirmation of the monophyletic family Achilixiidae outside the Achilidae-Derbidae clade, and the transfer of tribes Lyncidini and Amyclini to Dictyopharidae and the genusMadagascaritiato Fulgoridae. The time analyses based on 57 nuclear markers and 30 fossils dated the origin of crown Fulgoromorpha back to Guadalupian, Permian (∼263 Ma), close to the maximum constraint at 267.3 Ma, while applying an older root constraint resulted in an origin in Mississippian, Carboniferous (∼332 Ma). While future sampling of unstudied fauna in unexplored regions or habitats may change the topology, the current phylogenomic analysis will serve as a solid foundation for research into planthopper ecology, evolution, and significance.
Quantifying synthetic bacterial community composition with flow cytometry: efficacy in mock communities and challenges in co-cultures
Authors: Mermans Fabian , Chatzigiannidou Ioanna , Teughels Wim , Boon Nico 
Published: July 2024

AbstractDetermination of bacterial community composition in synthetic communities is critical for understanding microbial systems. The community composition is typically determined through bacterial plating or through PCR-based methods which can be labor-intensive, expensive or prone to bias. Simultaneously, flow cytometry has been suggested as a cheap and fast alternative. However, since the technique captures the phenotypic state of bacterial cells, accurate determination of community composition could be affected when bacteria are co-cultured. We investigated the performance of flow cytometry for quantifying oral synthetic communities and compared it to the performance of strain specific qPCR and 16S rRNA gene amplicon sequencing. Therefore, axenic cultures, mock communities and co-cultures of oral bacteria were prepared. Random forest classifiers trained on flow cytometry data of axenic cultures were used to determine the composition of the synthetic communities, as well as strain specific qPCR and 16S rRNA gene amplicon sequencing. Flow cytometry was shown to have a lower average root mean squared error and outperformed the PCR-based methods in even mock communities (flow cytometry: 0.11 ± 0.04; qPCR: 0.26 ± 0.09; amplicon sequencing: 0.15 ± 0.01). When bacteria were co-cultured, neither flow cytometry, strain specific qPCR and 16S rRNA gene amplicon sequencing resulted in similar community composition. Performance of flow cytometry was decreased compared to mock communities due to changing phenotypes. Finally, discrepancies between flow cytometry and strain specific qPCR were found. These findings highlight the challenges ahead for quantifying community composition in co-cultures by flow cytometry.ImportanceQuantification of bacterial composition in synthetic communities is crucial for understanding and steering microbial interactions. Traditional approaches like plating, strain specific qPCR and amplicon sequencing are often labor-intensive and expensive and limit high-throughput experiments. Recently, flow cytometry has been suggested as a swift and cheap alternative for quantifying communities and has been successfully demonstrated on simple bacterial mock communities. However, since flow cytometry measures the phenotypic state of cells, measurements can be affected by differing phenotypes. Especially changing phenotypes resulting from co-culturing bacteria can have a profound effect on the applicability of the technique in this context. This research illustrates the feasibility and challenges of flow cytometry for the determination of community structure in synthetic mock communities and co-cultures.
Multiple variants of IncF plasmid alleles discovered within single bacterial cells challenge previous assumptions
Authors: Ruzickova Michaela , Palkovicova Jana , Papousek Ivo , Cummins Max L , Djordjevic Steven P , Dolejska Monika 
Published: July 2024

AbstractIncF plasmids are diverse mobile genetic elements found in bacteria from the Enterobacteriaceae family and often carry critical antibiotic and virulence gene cargo. The classification of IncF plasmids using the plasmid Multi-Locus Sequence Typing (pMLST) tool compares the sequences of IncF alleles against a database to create a plasmid sequence type (ST). Accurate identification of plasmid STs is epidemiologically useful because it enables an assessment of the crucial IncF plasmid lineages associated with pandemic and emerging enterobacterial sequence types, inferring important information about specific bacterial lineages. Our initial observations showed discrepancies in IncF allele variants reported by pMLST in a collection of 898Escherichia coliST131 genomes. To evaluate the limitations of the pMLST tool, we interrogated an in-house and publicly available repository of 70324E. coligenomes of various STs and other Enterobacterales genomes (n=1247). All short-read genomes and representatives selected for long-read sequencing were used to assess allele variants and to compare the output with the real biological situation. When multiple allele variants occurred in a single bacterial genome, the python and web versions of the tool randomly selected one allele to report, leading to limited and inaccurate ST identification. Discrepancies were detected in 5804 of 72469 genomes (8.01%). Long read sequencing of 27 carefully selected genomes confirmed multiple IncF allele variants present on one plasmid, or two separate IncF plasmids present in a single bacterial cell. The pMLST tool was unable to accurately distinguish allele variants and their location on replicons using short-read nor long-read genome sequences.ImportancePlasmid sequence type is crucial for describing IncF plasmids due to their capacity to carry important antibiotic and virulence gene cargo and consequently due to their association with disease-causing enterobacterial lineages exhibiting resistance to clinically relevant antibiotics in humans and food animals. As a result, precise reporting of IncF allele variants in IncF plasmids is necessary. Comparison of the FAB formulae generated by the plasmid Multi-Locus Sequence Typing (pMLST) tool with annotated long-read genome sequences identified inconsistencies, including examples where multiple IncF allele variants were present on the same plasmid but missing in the FAB formula, or in cases where two IncF plasmids were detected in one bacterial cell and the pMLST output provided information only about one plasmid. Such inconsistencies may cloud interpretation of IncF plasmid replicon type in specific bacterial lineages or inaccurate assumptions of host strain clonality.
Coupling proximity biotinylation with genomic targeting to characterize locus-specific changes in chromatin environments
Authors: Tchara Pata-Eting Kougnassoukou , Loehr Jérémy , Lambert Jean-Philippe 
Published: July 2024

AbstractRegulating gene expression involves significant and frequent changes in the chromatin environment at the locus level, especially at regulatory sequences. However, their modulation in response to pharmacological treatments or pathological conditions remain mostly undetermined. Here, we report versatile locus-specific proteomics tools to address this knowledge gap, which combine the targeting ability of the CRISPR/Cas9 system and the protein-labelling capability of the highly reactive biotin ligases TurboID (in CasTurbo) and UltraID (in CasUltra). CasTurbo and CasUltra enabled rapid chromatin protein labelling under mild conditions at repetitive sequences like centromeres and telomeres, as well as non-amplified genes. We applied CasUltra to A375 melanoma cell lines to decipher the protein environment of theMYCpromoter and characterize the molecular effects of the bromodomain inhibitor JQ1, which targets bromodomain and extra-terminal (BET) proteins that regulateMYCexpression. We quantified the consequences of BET protein displacement from theMYCpromoter and found that it was associated with a considerable reorganisation of the chromatin composition. In addition, BET protein retention at theMYCpromoter was consistent with a model of increased JQ1 resistance. Thus, through the combination of proximity biotinylation and CRISPR-Cas9-dependent genomic targeting, CasTurbo and CasUltra have successfully demonstrated their utility in profiling the proteome associated with a genomic locus in living cells.In BriefKougnassoukou Tcharaet al. report the development and application of CasTurbo and CasUltra, two locus-specific proteomics tools that fuse catalytically dead Cas9 to the engineered biotin ligases TurboID and UltraID. These tools enabled the quantitative mapping of locus-specific chromatin remodelling due to pharmacological inhibition.HighlightsCasTurbo and CasUltra were developed for locus-specific label-free proteomicsCasTurbo mapped the proteins localized to the centromeres and telomeresProteins bound to theMYCpromoter were quantified in melanoma cells with CasUltraCasUltra is compatible with investigating pharmacological treatment effectsGraphical abstract
An aging-sensitive compensatory secretory phospholipase that confers neuroprotection and cognitive resilience
Authors: Vicidomini Cinzia , Goode Travis D. , McAvoy Kathleen M. , Yu Ruilin , Beveridge Conor H. , Iyer Sanjay N. , Victor Matheus B. , Leary Noelle , Evans Liam , Steinbaugh Michael J. , Lai Zon Weng , Lyon Marina C. , Silvestre Manuel Rico F.S , Bonilla Gracia , Sadreyev Ruslan I. , Walther Tobias C. , Sui Shannan Ho , Saido Takaomi , Yamamoto Kei , Murakami Makoto , Tsai Li-Huei , Chopra Gaurav , Sahay Amar 
Published: July 2024

AbstractBreakdown of lipid homeostasis is thought to contribute to pathological aging, the largest risk factor for neurodegenerative disorders such as Alzheimer’s Disease (AD). Cognitive reserve theory posits a role for compensatory mechanisms in the aging brain in preserving neuronal circuit functions, staving off cognitive decline, and mitigating risk for AD. However, the identities of such mechanisms have remained elusive. A screen for hippocampal dentate granule cell (DGC) synapse loss-induced factors identified a secreted phospholipase,Pla2g2f, whose expression increases in DGCs during aging.Pla2g2fdeletion in DGCs exacerbates aging-associated pathophysiological changes including synapse loss, inflammatory microglia, reactive astrogliosis, impaired neurogenesis, lipid dysregulation and hippocampal-dependent memory loss. Conversely, boostingPla2g2fin DGCs during aging is sufficient to preserve synapses, reduce inflammatory microglia and reactive gliosis, prevent hippocampal-dependent memory impairment and modify trajectory of cognitive decline. Ex vivo, neuronal-PLA2G2F mediates intercellular signaling to decrease lipid droplet burden in microglia. BoostingPla2g2fexpression in DGCs of an aging-sensitive AD model reduces amyloid load and improves memory. Our findings implicate PLA2G2F as a compensatory neuroprotective factor that maintains lipid homeostasis to counteract aging-associated cognitive decline.