bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging affects reprogramming of murine pulmonary capillary endothelial cells after lung injury
Authors: Truchi Marin , Gautier-Isola Marine , Savary Grégoire , Cadis Hugo , Scribe Célia , Baeri Alberto , Lingampally Arun , Magnone Virginie , Girard-Riboulleau Cédric , Arguel Marie-Jeanne , de Schutter Clémentine , Fassy Julien , Boukrout Nihad , Larrue Romain , Martin Nathalie , Rezzonico Roger , Pluquet Olivier , Perrais Michael , Hofman Véronique , Marquette Charles-Hugo , Hofman Paul , Günther Andreas , Ricard Nicolas , Barbry Pascal , Leroy Sylvie , Lebrigand Kevin , Bellusci Saverio , Cauffiez Christelle , Vassaux Georges , Pottier Nicolas , Mari Bernard 
Published: July 2023

ABSTRACTAging increases the risk of developing fibrotic diseases by hampering tissue regeneration after injury. Using longitudinal single-cell RNA-seq and spatial transcriptomics, here we compare the transcriptome of bleomycin-induced fibrotic lungs of young and aged mice, at 3 time points corresponding to the peak of fibrosis, regeneration and resolution. We find that lung injury shifts the transcriptomic profiles of three pulmonary capillary endothelial cells (PCEC) subpopulations. The associated signatures are linked to pro-angiogenic signaling with strongLrg1expression and do not progress similarly throughout the resolution process between young and old animals. Moreover, part of this set of resolution-associated markers is also detected in PCEC from samples of patients with idiopathic pulmonary fibrosis. Finally, we find that aging also alters the transcriptome of PCEC which display typical pro-fibrotic and pro-inflammatory features. We propose that age-associated alterations in specific PCEC subpopulations may interfere with the process of lung progenitor differentiation, thus contributing to the persistent fibrotic process typical of human pathology.
Beyond Correlation: Optimal Transport Metrics For Characterizing Representational Stability and Remapping in Neurons Encoding Spatial Memory
Authors: Aoun Andrew , Shetler Oliver , Raghuraman Radha , Rodriguez Gustavo A. , Hussaini S. Abid 
Published: July 2023

ABSTRACTSpatial representations in the entorhinal cortex (EC) and hippocampus (HPC) are fundamental to cognitive functions like navigation and memory. These representations, embodied in spatial field maps, dynamically remap in response to environmental changes. However, current methods, such as Pearson’s correlation coefficient, struggle to capture the complexity of these remapping events, especially when fields do not overlap, or transformations are non-linear. This limitation hinders our understanding and quantification of remapping, a key aspect of spatial memory function. To address this, we propose a family of metrics based on the Earth Mover’s Distance (EMD) as a versatile framework for characterizing remapping. Applied to both normalized and unnormalized distributions, the EMD provides a granular, noise-resistant, and rate-robust description of remapping. This approach enables the identification of specific cell types and the characterization of remapping in various scenarios, including disease models. Furthermore, the EMD’s properties can be manipulated to identify spatially tuned cell types and to explore remapping as it relates to alternate information forms such as spatiotemporal coding. By employing approximations of the EMD, we present a feasible, lightweight approach that complements traditional methods. Our findings underscore the potential of the EMD as a powerful tool for enhancing our understanding of remapping in the brain and its implications for spatial navigation, memory studies and beyond.
The Microspherule protein 1(MCRS1) homolog interacts with the Myb-like transcription factor DRMY1 and is essential for embryogenesis inArabidopsis thaliana
Authors: Huo Huan Howard , Luo Ming , Lee Yuh-Ru Julie , Liu Bo 
Published: July 2023

AbstractThe evolutionarily conserved Microspherule protein 1 (MCRS1) has diverse functions from transcriptional regulation to stabilization of microtubule minus ends in acentrosomal spindles in mammals. A previous study suggested that in the model plantArabidopsis thaliana, inactivation of an MCRS1 homolog gene led to aborted embryogenesis. To test whether this lethality was caused by defects associated with transcription or mitosis, we used the heterozygousmcrs1mutant to examine whether the gene was required for mitosis during gametogenesis. Results of reciprocal crosses between themcrs1mutant and the wild-type plant showed that theMCRS1gene was dispensable for mitotic cell divisions associated with the development of both male and female gametophytes. An MCRS1-GFP fusion protein was expressed in themcrs1mutant and suppressed the mutation as reported by restored growth. This functional fusion protein exclusively localized to interphase nuclei and became undetectable during mitosis before returning to the reforming daughter nuclei. Affinity purification of the MCRS1-GFP protein resulted in consistent recovery of the Myb-like transcription factor DRMY1 (Developmentally Regulated Myb-like1) but not microtubule-associated factors. The association was further supported by the evidence of a direct interaction in living cells. Hence, the plant MCRS1 was concluded to play a role in the gene transcription in sporophyte development.
How climate change and population growth will shape attendance and human-wildlife interactions at British Columbia parks
Authors: Weststrate Dayna K , Chhen Aimee , Mezzini Stefano , Safford Kirk , Noonan Michael J 
Published: July 2023

AbstractProtected areas are important for ecological conservation while simultaneously supporting culturally, and economically valuable tourism. However, excessive guest volumes strain operations and risk human-wildlife conflict, threatening the sustainability of nature-based tourism. Thus, park managers need to know what factors underpin attendance and how these might interact to shape future attendance. Using a decade of attendance records from 249 provincial parks, in British Columbia (BC), Canada, as well as 12 years of human-wildlife interactions (HWI) records at five national parks in BC, we modelled the impacts of weather conditions and population growth interact on park attendance and HWIs. We paired these models with climate change and population growth scenarios to generate projections of how attendance and HWIs will change throughout the century. Climate change is projected to result in more precipitation and higher temperatures, and, over this same time span, BC’s population is expected to grow substantially. Based on the observed relationship between attendance and weather, parks should anticipate a marked rise in visitors and HWIs especially during their respective peak seasons. These projections provide park managers with the information required for proactive management, ultimately contributing to the sustainability of recreation and tourism in protected areas.
Propagation path of a flowering cherry (Cerasus×yedoensis) cultivar ‘Somei-Yoshino’ traced by somatic mutations
Authors: Shirasawa Kenta , Esumi Tomoya , Itai Akihiro , Hatakeyama Katsunori , Takashina Tadashi , Yakuwa Takuji , Sumitomo Katsuhiko , Kurokura Takeshi , Fukai Eigo , Sato Keiichi , Shimada Takehiko , Shiratake Katsuhiro , Hosokawa Munetaka , Monden Yuki , Kusaba Makoto , Ikegami Hidetoshi , Isobe Sachiko 
Published: July 2023

AbstractFlowering cherry cultivar ‘Somei-Yoshino’ (Cerasus×yedoensis) has been clonally propagated and spread all around the world including Japan. ‘Somei-Yoshino’ is thought to be an interspecific hybrid derived fromC. spachianaandC. speciosa; however, its origin is unclear. Since somatic mutations are randomly induced in genomes and stably transmitted through generations, we aimed to identify somatic mutations in the genome of ‘Somei-Yoshino’ to trace its propagation path. A total of 46 ‘Somei-Yoshino’ clones were collected from all over Japan and subjected to whole-genome sequencing. The results revealed 684 single nucleotide variants, of which 71 were found in more than two clones. Clustering analysis of the 46 clones using these 71 variants revealed six groups, four of which contained 40 of the 46 clones. In addition, because each of the four clones closely planted in Ueno Park, Tokyo, Japan, clustered into the four different groups, we considered that these four clones could be the ancestors of the ‘Somei-Yoshino’ clones found in Japan. Furthermore, based on the comparison of mutant alleles with the genomes ofCerasusspecies, one of the four trees was concluded as the closest to the origin. Here, we propose that the origin of ‘Somei-Yoshino’ is a chimera derived from at least four somatic mutants.
Integration of variant annotations using deep set networks boosts rare variant association genetics
Authors: Clarke Brian , Holtkamp Eva , Öztürk Hakime , Mück Marcel , Wahlberg Magnus , Meyer Kayla , Munzlinger Felix , Brechtmann Felix , Hölzlwimmer Florian R. , Gagneur Julien , Stegle Oliver 
Published: July 2023

AbstractRare genetic variants can strongly predispose to disease, yet accounting for rare variants in genetic analyses is statistically challenging. While rich variant annotations hold the promise to enable well-powered rare variant association tests, methods integrating variant annotations in a data-driven manner are lacking. Here, we propose DeepRVAT, a model based on set neural networks that learns burden scores from rare variants, annotations, and phenotypes. In contrast to existing methods, DeepRVAT yields a single, trait-agnostic, nonlinear gene impairment score, enabling both risk prediction and gene discovery in a unified framework. On 34 quantitative and 26 binary traits, using whole-exome-sequencing data from UK Biobank, we find that DeepRVAT offers substantial increases in gene discoveries and improved replication rates in held-out data. Moreover, we demonstrate that the integrative DeepRVAT gene impairment score greatly improves detection of individuals at high genetic risk. Finally, we show that pre-trained DeepRVAT scores generalize across traits, opening up the possibility to conduct highly computationally efficient rare variant tests.
The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2
Authors: Pekar Jonathan E. , Lytras Spyros , Ghafari Mahan , Magee Andrew F. , Parker Edyth , Havens Jennifer L. , Katzourakis Aris , Vasylyeva Tetyana I. , Suchard Marc A. , Hughes Alice C. , Hughes Joseph , Robertson David L. , Dellicour Simon , Worobey Michael , Wertheim Joel O. , Lemey Philippe 
Published: July 2023

AbstractThe emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 has led to increased sampling of related sarbecoviruses circulating primarily in horseshoe bats. These viruses undergo frequent recombination and exhibit spatial structuring across Asia. Employing recombination-aware phylogenetic inference on bat sarbecoviruses, we find that the closest-inferred bat virus ancestors of SARS-CoV and SARS-CoV-2 existed just ∼1–3 years prior to their emergence in humans. Phylogeographic analyses examining the movement of related sarbecoviruses demonstrate that they traveled at similar rates to their horseshoe bat hosts and have been circulating for thousands of years in Asia. The closest-inferred bat virus ancestor of SARS-CoV likely circulated in western China, and that of SARS-CoV-2 likely circulated in a region comprising southwest China and northern Laos, both a substantial distance from where they emerged. This distance and recency indicate that the direct ancestors of SARS-CoV and SARS-CoV-2 could not have reached their respective sites of emergence via the bat reservoir alone. Our recombination-aware dating and phylogeographic analyses reveal a more accurate inference of evolutionary history than performing only whole-genome or single gene analyses. These results can guide future sampling efforts and demonstrate that viral genomic fragments extremely closely related to SARS-CoV and SARS-CoV-2 were circulating in horseshoe bats, confirming their importance as the reservoir species for SARS viruses.
Biodiversity monitoring in Europe: user and policy needs
Authors: Moersberger Hannah , Valdez Jose , Martin Juliette G. C. , Junker Jessica , Georgieva Ivelina , Bauer Silke , Beja Pedro , Breeze Tom D. , Fernandez Miguel , Fernández Néstor , Brotons Lluís , Jandt Ute , Bruelheide Helge , Kissling W. Daniel , Langer Christian , Liquete Camino , Lumbierres Maria , Solheim Anne Lyche , Maes Joachim , Morán-Ordóñez Alejandra , Moreira Francisco , Pe’er Guy , Santana Joana , Shamoun-Baranes Judy , Smets Bruno , Capinha César , McCallum Ian , Pereira Henrique M. , Bonn Aletta 
Published: July 2023

AbstractTo implement the goals of the 2030 Global Biodiversity Framework, the European Biodiversity Strategy and the EU Green Deal, biodiversity monitoring is a pivotal instrument to achieve accountability and progress in conservation. Monitoring efforts in Europe, however, suffer from gaps and biases in taxonomy, spatial coverage, and temporal resolution, resulting in fragmented and disconnected data which does not provide sufficient evidence for policy making. To assess user and policy needs in biodiversity monitoring, we employed with EuropaBON a four-step user-centred stakeholder engagement process, including an international public stakeholder workshop, a standardised online survey, semi-structured interviews, and an expert meeting with representatives of EU member states, the European Commission and the European Environment Agency. The resulting insights into national and European biodiversity monitoring schemes identify policy needs, current challenges and potential solutions. Based on this in-depth policy and science stakeholder assessment, we recommend the establishment of a European Biodiversity Observation Network through a permanent Biodiversity Monitoring and Coordinating Centre to optimise existing observation efforts, harmonise data, and enhance our ability to predict and respond to key challenges related to biodiversity loss in a changing climate in Europe.
A mean-field theory for predicting single polymer collapse induced by neutral crowders
Authors: Chaboche Quentin , Campos-Villalobos Gerardo , Giunta Giuliana , Dijkstra Marjolein , Cosentino-Lagomarsino Marco , Scolari Vittore F. 
Published: July 2023

AbstractMacromolecular crowding can induce the collapse of a single long polymer into a globular form due to depletion forces of entropic nature. This phenomenon has been shown to play a significant role in compacting the genome within the bacteriumEscherichia coliinto a well-defined region of the cell known as the nucleoid. Motivated by the biological significance of this process, numerous theoretical and computational studies have searched for the primary determinants of the behavior of polymer-crowder phases. However, our understanding of this process remains incomplete and there is debate on a quantitatively unified description. In particular, different simulation studies with explicit crowders have proposed different order parameters as potential predictors for the collapse transition. In this work, we present a comprehensive analysis of published simulation data obtained from different sources. Based on the common behavior we find in this data, we develop a unified phenomenological model that we show to be predictive. Finally, to further validate the accuracy of the model, we conduct new simulations on polymers of various sizes, and investigate the role of jamming of the crowders.
In Vivo Monitoring of Cellular Senescence by Photoacoustic and Fluorescence Imaging Utilizing a Nanostructured Organic Probe
Authors: Baker Andrew G. , Ou Hui-Ling , Hartono Muhamad , Popov Andrea Bistrović , Brown Emma L. , Joseph James , Golinska Monika , Sanghera Chandan , González-Gualda Estela , Macias David , Else Thomas R. , Greer Heather F. , Vernet Aude , Bohndiek Sarah E. , Fruk Ljiljana , Muñoz-Espín Daniel 
Published: July 2023

ABSTRACTSenescent cells accumulate in multiple age-related disorders, including cancer, exacerbating the pathological manifestations, and the eradication of these cells has emerged as a promising therapeutic strategy. Despite the impact of senescence in diseases, the development of tools to monitor the senescent burdenin vivoremains a challenge due to their suboptimal specificity, translatability, and tissue penetrance. Here, we have designed a nanostructured organic probe (NanoJaggs) based on biocompatible indocyanine green dye (ICG) building blocks forming J-aggregates, which possess distinct spectral properties allowing both fluorescence and photoacoustic tomography (PAT) detection. We show that NanoJaggs are taken up by an active process of endocytosis and exhibit selective accumulation at the lysosomal compartment in severalin vitromodels for senescence. Finally, NanoJagg probe is validated in twoin vivostudies including live PAT imaging and shows remarkable specificity to tumours with chemotherapy-induced senescence compared to untreated proliferative tumors.In vitro, ex vivoandin vivoall indicate that NanoJaggs are a clinically translatable tool for detection of senescence and their robust PAT signal makes them suitable for longitudinal monitoring of the senescent burden in solid tumors after chemo or radiotherapy.
Prediction of protein-RNA interactions from single-cell transcriptomic data
Authors: Fiorentino Jonathan , Armaos Alexandros , Colantoni Alessio , Tartaglia Gian Gaetano 
Published: July 2023

AbstractRNA-binding proteins play a crucial role in regulating RNA processing, yet our understanding of their interactions with coding and non-coding RNAs remains limited. Experimental studies are typically restricted to a small number of cell lines and a limited set of RNA-binding proteins (RBPs). Although computational methods based on sequence and structure can predict protein-RNA interactions accurately, they often lack the ability to consider cell-type-specific gene expression and the broader context of gene regulatory networks (GRNs).In the present study, we assess the performance of several GRN inference algorithms in predicting protein-RNA interactions from single-cell transcriptomic data, and we propose a pipeline, called scRAPID (single-cell transcriptomic-based RnA Protein Interaction Detection), that integrates these methods with thecatRAPID algorithm, which can identify direct physical interactions between RBPs and RNA molecules.Our approach demonstrates that RBP-RNA interactions can be inferred from single-cell transcriptomic data, with performances comparable or superior to those achieved for the well-established task of inferring transcription factor-target interactions. Notably, the incorporation ofcatRAPID significantly enhances the accuracy of identifying interactions, particularly with long non-coding RNAs, and enables the identification of hub RBPs and hub RNAs. Additionally, we show that interactions between RBPs can be detected based on their inferred RNA targets.We have made the software freely available athttps://github.com/tartaglialabIIT/scRAPID.
Crk/Crklregulates early angiogenesis in mouse embryos by accelerating endothelial cell maturation
Authors: Shi Lijie , Song Hansoo , Zhou Bin , Morrow Bernice E. 
Published: July 2023

AbstractRationaleUbiquitously expressed cytoplasmic adaptors CRK and CRKL mediate multiple signaling pathways in mammalian embryogenesis. They are also associated with cardiovascular defects occurring in Miller-Dieker syndrome and 22q11.2 deletion syndrome, respectively. The embryonic mesoderm contributes to the formation of the cardiovascular system, yet the roles thatCrkandCrklplay there are not understood on a single cell level.ObjectivesTo determine functions ofCrkandCrklin the embryonic mesoderm during early mouse vascular development. Secondly, we will examine the molecular mechanisms responsible for early embryonic endothelial cell (EC) defects by performing single cell RNA-sequencing (scRNA-seq) andin vivovalidation experiments.Methods and ResultsInactivation of bothCrkandCrkltogether usingMesp1Creresulted embryonic lethality with severe vascular defects. Although vasculogenesis appeared normal, angiogenesis was disrupted both in the yolk sac and embryo proper, leading to disorganized vascular networks. We performed scRNA-seq of theMesp1Cremesodermal lineage and found that there was upregulation of a great number of angiogenesis and cell migration related genes in ECs in the mutants, including NOTCH signaling genes such asDll4andHey1. Further bioinformatic analysis of EC subpopulations identified a relative increase in the number of more differentiated angiogenic ECs and decrease in EC progenitors. Consistent with this, we identified an expansion ofDll4expressing cells within abnormal arteries,in vivo. Also, our bioinformatic data indicates that there is dysregulated expression of lineage genes that promote EC differentiation causing accelerated cell fate progression during EC differentiation.ConclusionsOur results show thatCrkandCrklare crucial for regulating early embryonic angiogenesis. Combined inactivation ofCrk/Crklcaused precocious EC maturation with an increase of atypical differentiated angiogenic ECs and failed vascular remodeling. This is in part due to increased NOTCH signaling and altered expression of cell migration genes.
A Conserved Electrostatic Membrane-Binding Surface in Synaptotagmin-Like Proteins Revealed Using Molecular Phylogenetic Analysis and Homology Modeling
Authors: Chon Nara L. , Tran Sherleen , Miller Christopher S. , Lin Hai , Knight Jefferson D. 
Published: July 2023

AbstractProtein structure prediction has emerged as a core technology for understanding biomolecules and their interactions. Here, we combine homology-based structure prediction with molecular phylogenetic analysis to study the evolution of electrostatic membrane binding among vertebrate synaptotagmin-like proteins (Slps). Slp family proteins play key roles in the membrane trafficking of large dense-core secretory vesicles. Our previous experimental and computational study found that the C2A domain of Slp-4 (also called granuphilin) binds with high affinity to anionic phospholipids in the cytoplasmic leaflet of the plasma membrane through a large positively charged protein surface centered on a cluster of phosphoinositide-binding lysine residues. Because this surface contributes greatly to Slp-4 C2A domain membrane binding, we hypothesized that the net charge on the surface might be evolutionarily conserved. To test this hypothesis, the known C2A sequences of Slp-4 among vertebrates were organized by class (from mammalia to pisces) using molecular phylogenetic analysis. Consensus sequences for each class were then identified and used to generate homology structures, from which Poisson–Boltzmann electrostatic potentials were calculated. For comparison, homology structures and electrostatic potentials were also calculated for the five human Slp protein family members. The results demonstrate that the charge on the membrane-binding surface is highly conserved throughout the evolution of Slp-4, and more highly conserved than many individual residues among the human Slp family paralogs. Such molecular phylogenetic-driven computational analysis can help to describe the evolution of electrostatic interactions between proteins and membranes which are crucial for their function.Impact statementThe interior surface of eukaryotic plasma membranes is negatively charged, and many proteins that bind to it have correspondingly evolved a positively charged face. Here, we use techniques from evolutionary biology and computational biophysics to study the conservation of this positively charged surface in an important protein family. We find that the overall surface charge is highly conserved, more so than individual amino acids, consistent with its important role in electrostatic interaction with the membrane.