bluuebunny/crossref_metadata_2025_split huggingface dataset:
A compound PCP scheme underlies sequential rosettes-based cell intercalation
Authors: Xu Yichi , Cheng Yunsheng , Chen Allison T. , Bao Zhirong 
Published: November 2022

SUMMARYSequential rosettes are a type of collective cell behavior recently discovered in theC. elegansembryo to mediate directional cell migration through sequential formation and resolution of multicellular rosettes involving the migrating cell and its neighboring cells along the way. Here we show that a Planar Cell Polarity (PCP)-related polarity scheme regulates sequential rosettes, which is distinct from the known mode of how PCP regulates multicellular rosettes in the process of convergent extension. Specifically, non-muscle myosin (NMY) localization and edge contraction are perpendicular to that of Van Gogh as opposed to colocalizing with Van Gogh. Further analyses suggest a two-component polarity scheme: one being the canonical PCP pathway with MIG-1/Frizzled and VANG-1/Van Gogh localized to the vertical edges, the other being MIG-1/Frizzled and NMY-2 localized to the midline/contracting edges. Both MIG-1/Frizzled and VANG-1/Van Gogh are required for NMY-2 localization and contraction of the midline edges, but in redundancy with LAT-1/Latrophilin, an adhesion GPCR which has not been shown to regulate multicellular rosettes. Our results establish a distinct mode of PCP-mediated cell intercalation and shed light on the versatile nature of PCP pathway.
Immune Response following FLASH and Conventional Radiation in Diffuse Midline Glioma (DMG)
Authors: Padilla Oscar , Minns Hanna E. , Wei Hong-Jian , Fan Weijia , Webster-Carrion Andrea , Tazhibi Masih , McQuillan Nicholas M. , Zhang Xu , Gallitto Matthew , Yeh Rebecca , Zhang Zhiguo , Hei Tom K. , Szalontay Luca , Pavisic Jovana , Tan Yuewen , Deoli Naresh , Garty Guy , Garvin James H. , Canoll Peter D. , Vanpouille-Box Claire , Menon Vilas , Olah Marta , Rabadan Raul , Wu Cheng-Chia , Gartrell Robyn D. 
Published: November 2022

ABSTRACTPurposeDiffuse Midline Glioma (DMG) is a fatal tumor traditionally treated with radiotherapy (RT) and previously characterized as having a non-inflammatory tumor immune microenvironment (TIME). FLASH is a novel RT technique using ultra-high dose rate, which is associated with decreased toxicity and effective tumor control. However, the effect of FLASH and conventional (CONV) RT on the DMG TIME have not yet been explored.MethodsHere, we perform single-cell RNA sequencing and flow cytometry on immune cells isolated from an orthotopic syngeneic murine model of brainstem DMG following the use of FLASH (90Gy/sec) or CONV (2Gy/min) dose-rate RT, and compare to unirradiated tumor (SHAM).ResultsAt day 4 post-RT, FLASH exerts similar effects as CONV in the predominant microglial (MG) population, including the presence of two activated subtypes. However, at day 10 post-RT, we observe a significant increase in type 1 interferon alpha receptor (IFNAR+) in MG in CONV and SHAM compared to FLASH. In the non-resident myeloid clusters of macrophages (MACs) and dendritic cells (DCs), we find increased type 1 interferon (IFN1) pathway enrichment for CONV compared to FLASH and SHAM by scRNA-seq. We observe this trend by flow cytometry at day 4 post-RT in IFNAR+ MACs and DCs, which equalizes by day 10 post-RT. DMG control and murine survival are equivalent between RT dose rates.ConclusionOur work is the first to map CONV and FLASH immune alterations of the DMG TIME with single-cell resolution. While DMG tumor control and survival are similar between CONV and FLASH, we find that changes in immune compartments differ over time. Importantly, while both RT modalities increase IFN1, we find that the timing of this response is cell-type and dose-rate dependent. These temporal differences, particularly in the context of tumor control, warrant further study.
Feeding and growth variations affectδ13C andδ15N budgets during ontogeny in a lepidopteran larva
Authors: Charberet Samuel , Maria Annick , Siaussat David , Gounand Isabelle , Mathieu Jérôme 
Published: November 2022

AbstractIsotopes are widely used in ecology to study food webs and physiology. The fractionation observed between trophic levels in nitrogen and carbon isotopes, explained by isotopic biochemical selectivity, is subject to important within-trophic level variations, leading to imprecision in trophic level estimation. Understanding the drivers of these variations is thus important to improve the study of food webs. In this study, we characterized this variation by submittingSpodoptera littoralislarvae to a gradient of starvation levels, a factor that we hypothesized would change the trophic fractionation between individuals. The various growth rates that were induced from these starvation levels resulted in a ~ 1-1.5‰ within-trophic level variation of the trophic fractionation in both carbon and nitrogen, which is substantial compared to the 3-4‰classically associated with between-trophic levels variations. Hence starved animals sampledin naturamay be ranked at a higher trophic level than they really are. We were able to gain an understanding of the effect of growth rate on isotopes fluxes between three easy-to-measure biological materials, food, organism and its wastes (frass), giving insight into physiological processes at play but also conveying helpful information to the sampling framework of field studies.
FUS modulates the level of ribosomal RNA modifications by regulating a subset of snoRNA expression
Authors: Gawade Kishor , Plewka Patrycja , Häfner Sophia J , Lund Anders H , Marchand Virginie , Motorin Yuri , Szczesniak Michal W , Raczynska Katarzyna D 
Published: November 2022

ABSTRACTFUS is a multifunctional protein involved in many aspects of RNA metabolism, including transcription, splicing, translation, miRNA processing, and replication-dependent histone gene expression. In this paper, we show that FUS depletion results in differential expression of numerous small nucleolar RNAs (snoRNAs) that guide 2’-O methylation (2’-O-Me) and pseudouridylation of specific positions in ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). Using RiboMeth-seq and HydraPsiSeq for the profiling of 2’-O-Me and pseudouridylation status of rRNA species, we demonstrated considerable hypermodification at several sites in HEK293T and SH-SY5Y cells with FUS knockout (FUS KO) compared to wild-type cells. We observed a similar direction of changes in rRNA modification in differentiated SH-SY5Y cells with the FUS mutation (R495X) related to the severe disease phenotype of amyotrophic lateral sclerosis (ALS). Furthermore, the pattern of modification of some rRNA positions was correlated with the abundance of corresponding guide snoRNAs in FUS KO and FUS R495X cells. Our findings reveal a new role for FUS in modulating the modification pattern of rRNA molecules, that in turn might generate ribosome heterogeneity and constitute a fine-tuning mechanism for translation efficiency/fidelity. Therefore, we suggest that increased levels of 2’-O-Me and pseudouridylation at particular positions in rRNAs from cells with the ALS-linked FUS mutation may represent a possible new translation-related mechanism that underlies disease development and/or progression.
A live cell protein complementation assay for ORFeome-wide probing of human HOX interactomes
Authors: Jia Yunlong , Reboulet Jonathan , Gillet Benjamin , Hughes Sandrine , Forcet Christelle , Tribollet Violaine , Sleiman Nawal Hadj , Kundlacz Cindy , Vanacker Jean-Marc , Bleicher Françoise , Merabet Samir 
Published: November 2022

AbstractBiological pathways rely on the formation of intricate protein interaction networks called interactomes. Getting a comprehensive map of interactomes implies developing tools that allow capturing transient and low affinity protein-protein interactions (PPIs) in live conditions. Here we present an experimental strategy, Cell-PCA (Cell Protein Complementation Assay), which is based on BiFC (Bimolecular Fluorescence Complementation) and high throughput sequencing for ORFeome-wide analyses of different interactomes in the same live cell context. The specificity and sensitivity of Cell-PCA was established by using a wild type and a single amino-acid mutated HOXA9 protein, and the approach was subsequently applied for seven additional human HOX proteins. These proof-of-concept experiments revealed novel molecular properties of HOX interactomes and led to the identification of a novel cofactor of HOXB13 for promoting its proliferative activity in a cancer cell context. Taken together, our work demonstrates that Cell-PCA is pertinent for revealing and, importantly, comparing interactomes between different or highly related bait proteins in the same cell context.
Effects of microRNA-mediated negative feedback on gene expression noise
Authors: Adhikary Raunak , Roy Arnab , Jolly Mohit Kumar , Das Dipjyoti 
Published: November 2022

AbstractMicro-RNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally in eukaryotes by binding with target mRNAs and preventing translation. miRNA-mediated feedback motifs are ubiquitous in various genetic networks which control cellular decision-making. A key question is how such a feedback mechanism may affect gene expression noise. To answer this, we have developed a mathematical model to study the effects of a miRNA-dependent negative feedback loop on mean expression and noise in target mRNAs. Combining analytics and simulations, we show the existence of an expression threshold demarcating repressed and expressed regimes in agreement with earlier studies. The steady-state mRNA distributions are bimodal near the threshold, where copy numbers of mRNAs and miRNAs exhibit enhanced anticorrelated fluctuations. Moreover, variation of negative-feedback strength shifts the threshold locations and modulates the noise profiles. Notably, the miRNA-mRNA binding affinity and feedback strength collectively shape the bimodality. We also compare our model with a direct auto-repression motif, where a gene produces its own repressor. Auto-repression fails to produce bimodal mRNA distributions as found in miRNA-based indirect repression, suggesting the crucial role of miRNAs in creating phenotypic diversity. Together, we demonstrate how miRNA-dependent negative feedback modifies the expression threshold and leads to a broader parameter regime of bimodality compared to the no-feedback case.
Peyer’s Patch B cells undergo cell death via neutrophil-released toxic DNA following sterile tissue injury
Authors: Tuz Ali A , Beer Alexander , Gallert Markus , Ttoouli Dimitris , Ghosh Susmita , Sata Sai P , Kraus Andreas , Zwirnlein Franziska , Kaygusuz Viola , Lakovic Vivian , Qefalia Altea , Antler Medina , Korste Sebastian , Kaltwasser Britta , Abdelrahman Hossam , Mohamud-Yusuf Ayan , Wang Chen , Haeusler Lars , Lueong Smiths , Stenzel Martin , Frank Benedikt , Köhrmann Martin , Siveke Jens , Totzeck Matthias , Hoffmann Daniel , Grüneboom Anika , Hagemann Nina , Hasenberg Anja , Sickmann Albert , Chen Jianxu , Hermann Dirk M , Gunzer Matthias , Singh Vikramjeet 
Published: November 2022

SummaryLymphocyte contraction (LC) in central immune organs is a concomitant of sterile tissue injury, for example after stroke. Intestinal Peyer’s patches (PP) harbor large numbers of B cells, but how sterile tissue injury leads to LC in PP has not been explored. We observed rapid and macroscopically evident shrinkage of PP after stroke and myocardial infarction. Light-sheet fluorescence microscopy and flow cytometry revealed a strong reduction in the number of PP-resident B cells. Mechanistically, tissue injury triggered the activation of neutrophils that released B cell-toxic neutrophil extracellular traps (NETs) decorated with citrullinated histone-H3. Antibody-mediated or genetically induced neutrophil-loss, NETs-degradation or blockade of their generation completely reversed B cell loss and preserved the tissue architecture of PP. We also found NET-like elements in human post-stroke plasma. Hence, we propose that targeting NET-generation or -function counteracts post-injury B cell contraction in PP and thereby maintains immune homeostasis at mucosal barriers.In briefHigh numbers of B cells reside in the intestinal Peyer’s patches. Tuz et al. revealed that in response to sterile tissue injury, activated neutrophils release histone-decorated DNA into the circulation which induces B cell death. The loss of B cells results in the shrinkage of Peyer’s patches and reduced amounts of secretory IgA.HighlightsStroke and myocardial infarction induce the melting of Peyer’s patchLight-sheet microscopy and cytometry revealed B cell loss in Peyer’s patchPost-injury activated neutrophils release NETs and trigger B cell deathInhibition of NETs rescues B cell loss and degeneration of Peyer’s patch
Stomatal density affects rice mesophyll cell size and shape and modulates a conserved pattern of cells through the leaf
Authors: Jen Sloan , Saranrat Im-Chai , Ngai Qi Yang , Yi Xiao , Jodie Armand , Wilson Matthew J. , Xin-Guang Zhu , Fleming Andrew J. 
Published: November 2022

ABSTRACTThe structure of the mesophyll influences how light, CO2and water travels inside a leaf, affecting the rates of both photosynthesis and transpiration. Recent studies in wheat and Arabidopsis have shown that the structure of the mesophyll is influenced by the density and activity of stomata, consistent with the hypothesis that gas flow via stomata can modulate internal cell growth and separation to co-ordinate leaf structure and function. To investigate whether this also occurs in rice, a staple food crop for a large fraction of the world’s population, we examined mesophyll structure in rice mutants with altered stomatal density. Our data show that stomatal function modulates mesophyll structure in rice. Variation in the degree of mesophyll lobing made a major contribution to altered mesophyll structure, suggesting that modified leaf gas flux through stomata influences an aspect of cell shape directly linked to gas exchange capacity in rice. In addition, our analysis revealed a previously unreported underlying pattern in cell size, shape and axiality across layers of the rice mesophyll, which further investigation revealed is present in a range of rice species and cultivars. The potential origin and significance of this mesophyll patterning are discussed.HIGHLIGHTWe describe a previously unreported cellular pattern in rice leaves and show that it is modulated by stomata. These results shed new light on leaf structure and function.
Complete mitochondrial genome and draft chloroplastic genome of Northern AtlanticHaslea ostrearia(Gaillon/Bory) Simonsen, 1974 (Naviculaceae, Bacillariophyceae)
Authors: Peticca Aurelie , Fodil Mostefa , Gateau Helene , Mouget Jean-Luc , Sabot Francois , Chenais Benoit , Casse Nathalie 
Published: November 2022

ABSTRACTThe first completed, circular mitochondrial genome and the first draft chloroplastic genome of Northern Atlantic blue diatomHaslea ostrearia(Naviculaceae, Bacillariophyceae) are described. The mitochondrial genome is composed of 38,696 bases and contains 64 genes, including 31 protein-coding genes (CDS), 2 ribosomal RNA (rRNA) genes and 23 transfer RNA (tRNA) genes. For the chloroplast, the genome is composed of 130,200 bases with 169 genes (131 CDS, 6 rRNA genes, 31 tRNA genes, and 1 transfermessenger RNA (tmRNA) gene). Phylogenetic trees suggest the proximity of allH. ostreariastrains yet available and the possibility to use these genomes as future references.
Neurobehavioral precursors of compulsive cocaine-seeking in dual fronto-striatal circuits
Authors: Jones Jolyon A. , Belin-Rauscent Aude , Jupp Bianca , Fouyssac Maxime , Sawiak Stephen J. , Zuhlsdorff Katharina , Zhukovsky Peter , Hebdon Lara , Sanchez Clara Velazquez , Robbins Trevor W. , Everitt Barry J. , Belin David , Dalley Jeffrey W. 
Published: November 2022

AbstractOnly some individuals using drugs recreationally eventually become addicted, and persist in drug seeking and taking despite adverse consequences. The neurobehavioral determinants of this individual vulnerability have not been fully elucidated. We report that in drug naïve rats the future tendency to develop compulsive cocaine seeking is characterised by behavioral stickiness-related functional hypoconnectivity between the prefrontal cortex and posterior dorsomedial striatum in combination with impulsivity-related structural alterations in the infralimbic cortex, anterior insula and nucleus accumbens. These findings show that the vulnerability to develop compulsive cocaine seeking behavior stems from pre-existing structural or functional changes in two distinct cortico-striatal systems that underlie deficits in impulse control and goal-directed behavior.
Computational design of BclxL inhibitors that target transmembrane domain interactions
Authors: Duart Gerard , Elazar Assaf , Weinstein Jonathan J. , Gadea-Salom Laura , Ortiz-Mateu Juan , Fleishman Sarel J. , Mingarro Ismael , Martinez-Gil Luis 
Published: November 2022

AbstractSeveral methods have been developed to explore interactions among water-soluble proteins or regions of proteins. However, techniques to target transmembrane domains have not been examined thoroughly. Here we developed a novel computational approach to design transmembrane sequences that specifically modulate protein-protein interactions in the membrane. To illustrate this method we demonstrated that BclxL can interact with other members of the Bcl2 family through the transmembrane domain and that these interactions are necessary for BclxL control of cell death. Next, we designed sequences that specifically recognize and sequester the transmembrane domain of BclxL. Hence, we were able to prevent BclxL intra-membrane interactions and cancel its anti-apoptotic effect. These results advance our understanding of protein-protein interactions in membranes and provide new means to modulate them. Moreover, the success of our approach may trigger the development of a new generation of inhibitors targeting interactions between transmembrane domains.
Ibex: Variational autoencoder for single-cell BCR sequencing
Authors: Borcherding Nicholas , Sun Bo , DeNardo David , Brestoff Jonathan R. 
Published: November 2022

AbstractSummaryB cells are critical for adaptive immunity and are governed by the recognition of an antigen by the B cell receptor (BCR), a process that drives a coordinated series of signaling events and modulation of various transcriptional programs. Single-cell RNA sequencing with paired BCR profiling could offer insights into numerous physiological and pathological processes. However, unlike the plethora of single-cell RNA analysis pipelines, computational tools that utilize single-cell BCR sequences for further analyses are not yet well developed. Here we report Ibex, which vectorizes the amino acid sequence of the complementarity-determining region 3 (cdr3) of the immunoglobulin heavy and light chains, allowing for unbiased dimensional reduction of B cells using their BCR repertoire. Ibex is implemented as an R package with integration into both the Seurat and Single-Cell Experiment framework, enabling the incorporation of this new analytic tool into many single-cell sequencing analytic workflows and multimodal experiments.Availability and ImplementationIbex is available as an R package athttps://github.com/ncborcherding/Ibex. Reproducible code and data for the figure appearing in the manuscript are available athttps://github.com/ncborcherding/Ibex.manuscript. A companion TCR-based approach is available athttps://github.com/ncborcherding/Trex.
Neural signatures of reading-related orthographic processing in braille
Authors: Liu Yun-Fei , Rapp Brenda , Bedny Marina 
Published: November 2022

AbstractBlind readers use a tactile reading systems consisting of raised dot arrays: braille/⠃⠗⠇. How does the human brain implement reading by touch? The current study looked for signatures of reading-specific orthographic processes in braille, separate from low-level somatosensory responses and semantic retrieval. Of specific interest were responses in posterior parietal cortices (PPC), because of their role in high-level tactile perception. Congenitally blind, proficient braille readers read real words and pseudowords by touch while undergoing fMRI. We leveraged the system of contractions in English braille, where one or more braille cells can represent combinations of English print letters (e.g., “ing” ⠬, “one” ⠐⠕), making it possible to separate physical and uncontracted letter-length. All words in the study consisted of 4 braille cells, but their corresponding Roman spellings varied from 4 to 7 letters (e.g., “con-c-er-t” ⠒⠉⠻⠞. contracted: 4 cells; uncontracted: 7 letters). We found that the bilateral supramarginal gyrus (SMG) in the PPC increased its activity as the uncontracted word length increased. By contrast, in the hand region of primary somatosensory cortex (S1), activity increased as a function of a low-level somatosensory feature: dot-number per word. The PPC also showed greater response to pseudowords than real words and distinguished between real and pseudowords in multi-voxel-pattern analysis. Parieto-occipital, early visual and ventral occipito-temporal, as well as prefrontal cortices also showed sensitivity to the real-vs-pseudoword distinction. We conclude that PPC is involved in sublexical orthographic processing for braille, possibly due to braille’s tactile modality.Significance statementBlind readers use tactile reading systems of raised dot arrays: braille. To identify signatures of orthographic processing for reading by touch, and dissociate it from tactile and linguistic process, we leveraged the system of contractions in English braille, where one or more braille characters represents combinations of English print letters. Blind proficient braille readers read real words and pseudowords during fMRI scans. While all words consisted of 4 braille characters, the uncontracted spelling ranged from 4-7 letters. Activity in bilateral-posterior-parietal cortices, just posterior to primary-somatosensory cortex, increased with uncontracted word length, independent of tactile complexity (number of raised dots per word). By contrast, primary-somatosensory activity increased with tactile complexity. The posterior-parietal cortices contribute to tactile reading.
An untargeted metabolomics approach to characterize dissolved organic matter in groundwater of the Samail Ophiolite
Authors: Seyler Lauren M. , Kraus Emily A. , McLean Craig , Spear John R. , Templeton Alexis S. , Schrenk Matthew O. 
Published: November 2022

AbstractThe process of serpentinization supports life on Earth and gives rise to the habitability of other worlds in our Solar System. While numerous studies have provided clues to the survival strategies of microbial communities in serpentinizing environments on the modern Earth, characterizing microbial activity in such environments remains challenging due to low biomass and extreme conditions. Here, we use an untargeted metabolomics approach to characterize dissolved organic matter in groundwater in the Samail Ophiolite, the largest and best characterized example of actively serpentinizing uplifted ocean crust and mantle. We found that dissolved organic matter composition is strongly correlated with both fluid type and microbial community composition, and that the fluids that were most influenced by serpentinization contained the greatest number of unique compounds, none of which could be identified using the current metabolite databases. Using metabolomics in conjunction with metagenomic data, we detected numerous products and intermediates of microbial metabolic processes and identified potential biosignatures of microbial activity, including pigments, porphyrins, quinones, fatty acids, and metabolites involved in methanogenesis. Metabolomics techniques like the ones used in this study may be used to further our understanding of life in serpentinizing environments, and aid in the identification of biosignatures that can be used to search for life in serpentinizing systems on other worlds.