bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origin and adult renewal of the gut lacteal musculature from villus myofibroblasts
Authors: Sanketi Bhargav D. , Mantri Madhav , Huang Liqing , Tavallaei Mohammad A. , Hu Shing , Wang Michael F. Z. , De Vlaminck Iwijn , Kurpios Natasza A. 
Published: January 2023

AbstractIntestinal smooth muscles are the workhorse of the digestive system. Inside the millions of finger-like intestinal projections called villi, strands of smooth muscle cells contract to propel absorbed dietary fats through the adjacent lymphatic vessel, called the lacteal, sending fats into the blood circulation for energy production. Despite this vital function, how villus smooth muscles form, how they assemble alongside lacteals, and how they repair throughout life remain unknown. Here we combine single-cell RNA sequencing of the mouse intestine with quantitative lineage tracing to reveal the mechanisms of formation and differentiation of villus smooth muscle cells. Within the highly regenerative villus, we uncover a local hierarchy of subepithelial fibroblast progenitors that progress to become mature smooth muscle fibers, via an intermediate contractile myofibroblast-like phenotype. This continuum persists in the adult intestine as the major source of renewal of villus smooth muscle cells during adult life. We further found that the NOTCH3-DLL4 signaling axis governs the assembly of villus smooth muscles alongside their adjacent lacteal, and we show that this is necessary for gut absorptive function. Overall, our data shed light on the genesis of a poorly defined class of intestinal smooth muscle and pave the way for new opportunities to accelerate recovery of digestive function by stimulating muscle repair.
CATD: A reproducible pipeline for selecting cell-type deconvolution methods across tissues
Authors: Pournara Anna Vathrakokoili , Miao Zhichao , Beker Ozgur Yilimaz , Nolte Nadja , Brazma Alvis , Papatheodorou Irene 
Published: January 2023

AbstractCell-type deconvolution methods aim to infer cell composition from bulk transcriptomic data. The proliferation of developed methods, coupled with inconsistent results obtained in many cases, highlights the pressing need for guidance in the selection of appropriate methods. Additionally, the growing accessibility of single-cell RNA sequencing datasets, often accompanied by bulk expression from related samples, enable the benchmark of existing methods. In this study, we conduct a comprehensive assessment of 31 methods, utilising single-cell RNA-sequencing data from diverse human and mouse tissues. Employing various simulation scenarios, we reveal the efficacy of regression-based deconvolution methods, highlighting their sensitivity to reference choices. We investigate the impact of bulk-reference differences, incorporating variables such as sample, study and technology. We provide validation using a gold standard dataset from mononuclear cells and suggest a consensus prediction of proportions when ground truth is not available. We validated the consensus method on data from the stomach and studied its spillover effect. Importantly, we propose the use of the Critical Assessment of Transcriptomic Deconvolution (CATD) pipeline which encompasses functionalities for generating references and pseudo-bulks and running implemented deconvolution methods. CATD streamlines simultaneous deconvolution of numerous bulk samples, providing a practical solution for speeding up the evaluation of newly developed methods.Availability:https://github.com/Papatheodorou-Group/CATD_snakemake
Phage-specific immune responses impair efficacy of phage therapy targeting VRE in a murine model
Authors: Berkson Julia D. , Allen Garrison B. , Schubert Alyxandria M. , Dunbar Kristin E. , Coryell Michael P. , Sava Rosa L. , Gao Yamei , Wate Claire E. , Hastie Jessica L. , Zimmermann Sally K. , Carlson Paul E. 
Published: January 2023

AbstractAntimicrobial resistant bacteria are an emerging and prevalent global threat with an urgent need for alternative therapies. Bacteriophage (phage) therapy is a promising approach to address these infections that has gained renewed interest in recent years. Despite this, questions remain regarding the therapeutic use of phages, including the impact that the immune response may have on phage therapy, particularly when this treatment is administered long-term or when reusing a specific phage treatment in a single individual. To investigate this, we developed a mouse model to assess phage treatment using a cocktail of five phages from theMyoviridaeandSiphoviridaefamilies that target vancomycin-resistant enterococcus (VRE) gut colonization. Phage cocktail treatment significantly reduced the intestinal bacterial burden of VRE in mice. We characterized innate and adaptive immune responses elicited against the phage cocktail after one and multiple exposures, respectively. While minimal innate responses were observed after phage administration, two courses of phage therapy induced phage-specific neutralizing antibodies and appeared to accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induced a more robust neutralizing antibody response than the siphophages. Proteins targeted by phage-specific antibodies were also identified from each phage family of the cocktail. Importantly, we show that this anti-phage immunity reduced the effectiveness of the phage cocktail in our murine model, leading to significantly higher fecal bacterial burden following repeat treatment. Collectively, this study shows the immune system has the potential to impede effectiveness of phage therapy and that the phage-specific immune responses can differ significantly between phages. These findings can help inform decisions about inclusion of specific phages in cocktails for future studies.
Decomposing drivers in avian insectivory: large-scale effects of climate, habitat and bird diversity
Authors: Schillé Laura , Valdés-Correcher Elena , Archaux Frédéric , Bălăcenoiu Flavius , Bjørn Mona Chor , Bogdziewicz Michal , Boivin Thomas , Branco Manuela , Damestoy Thomas , de Groot Maarten , Dobrosavljević Jovan , Duduman Mihai-Leonard , Dulaurent Anne-Maïmiti , Green Samantha , Grünwald Jan , Eötvös Csaba Béla , Faticov Maria , Fernandez-Conradi Pilar , Flury Elisabeth , Funosas David , Galmán Andrea , Gossner Martin M. , Gripenberg Sofia , Grosu Lucian , Hagge Jonas , Hampe Arndt , Harvey Deborah , Houston Rick , Isenmann Rita , Kavčič Andreja , Kozlov Mikhail V. , Lanta Vojtech , Le Tilly Bénédicte , Vaamonde Carlos Lopez , Mallick Soumen , Mäntylä Elina , Mårell Anders , Milanović Slobodan , Molnár Márton , Moreira Xoaquín , Moser Valentin , Mrazova Anna , Musolin Dmitrii L. , Perot Thomas , Piotti Andrea , Popova Anna V. , Prinzing Andreas , Pukinskaya Ludmila , Sallé Aurélien , Sam Katerina , Sedikhin Nickolay V. , Shabarova Tanja , Tack Ayco J. M. , Thomas Rebecca , Thrikkadeeri Karthik , Toma Dragoș , Vaicaityte Grete , van Halder Inge , Varela Zulema , Barbaro Luc , Castagneyrol Bastien 
Published: January 2023

AbstractAimClimate is a major driver of large scale variability in biodiversity, as a likely result of more intense biotic interactions under warmer conditions. This idea fuelled decades of research on plant-herbivore interactions, but much less is known about higher-level trophic interactions. We addressed this research gap by characterizing both bird diversity and avian predation along a climatic gradient at the European scale.LocationEurope.TaxonInsectivorous birds and pedunculate oaks.MethodsWe deployed plasticine caterpillars in 138 oak trees in 47 sites along a 19° latitudinal gradient in Europe to quantify bird insectivory through predation attempts. In addition, we used passive acoustic monitoring to (i) characterize the acoustic diversity of surrounding soundscapes; (ii) approximate bird abundance and activity through passive acoustic recordings and (iii) infer both taxonomic and functional diversity of insectivorous birds from recordings.ResultsThe functional diversity of insectivorous birds increased with warmer climates. Bird predation increased with forest cover and bird acoustic activity but decreased with mean annual temperature and functional richness of insectivorous birds. Contrary to our predictions, climatic clines in bird predation attempts were not directly mediated by changes in insectivorous bird diversity or acoustic activity, but climate and habitat still had independent effects on predation attempts.Main conclusionsOur study supports the hypothesis of an increase in the diversity of insectivorous birds towards warmer climates, but refutes the idea that an increase in diversity would lead to more predation and advocates for better accounting for activity and abundance of insectivorous birds when studying the large-scale variation in insect-tree interactions.
A decade of hidden phytoplasmas unveiled through citizen science
Authors: Brochu Anne-Sophie , Dionne Antoine , Fall Mamadou Lamine , Pérez-López Edel 
Published: January 2023

ABSTRACTClimate change is impacting agriculture in many ways, and a contribution from all is required to reduce the imminent loses related to it. Recently, it has been showed that citizen science could be a way to trace the impact of climate change. However, how can citizen science be applied in plant pathology? Here, using as an example a decade of phytoplasma-related diseases reported by growers, agronomists, citizens in general, and confirmed by a government laboratory, we explore a new way of valuing plant pathogens monitoring data deriving from land-users or stakeholders. Through this collaboration we found that in the last decade thirty-four hosts have been affected by phytoplasmas, nine, thirteen and five of these plants were, for the first time, reported phytoplasma hosts in Eastern Canada, in Canada and worldwide, respectively. Another finding of great impact is the first report of a ‘Ca. P. phoenicium’-related strain in Canada, while ‘Ca. P. pruni’ and ‘Ca. P. pyri’ was reported for the first time in Eastern Canada. These findings will have a great impact in the management of phytoplasmas and their insect vectors. Using these insect-vectored bacterial pathogens, we show the needs of new strategies that allow a fast and accurate communication between concerned citizens and those institutions confirming their observations.Abstract Figure
DESP: Demixing Cell State Profiles from Dynamic Bulk Molecular Measurements
Authors: Youssef Ahmed , Paul Indranil , Crovella Mark , Emili Andrew 
Published: January 2023

AbstractThere is wide interest to determine the dynamic expression of proteins and other molecules that drive phenotypic remodeling in development and pathobiology, but due to technical limitations these systems remain largely unexplored at the foundational resolution of the underlying cell states. Here, we presentDESP, a novel algorithm that leverages independent estimates of cell state proportions, such as from single-cell RNA-sequencing or cell sorting, to resolve the relative contributions of cell states to bulk molecular measurements, most notably quantitative proteomics, recorded in parallel. We appliedDESPto an in-vitro model of the epithelial-to-mesenchymal transition and demonstrated its ability to accurately reconstruct cell state signatures from bulk-level measurements of both the proteome and transcriptome providing insights into transient regulatory mechanisms.DESPprovides a generalizable computational framework for modeling the relationship between bulk and single-cell molecular measurements, enabling the study of proteomes and other molecular profiles at the cell state-level using established bulk-level workflows.
Linking genetic and environmental factors through marker effect networks to understand trait plasticity
Authors: Coletta Rafael Della , Liese Sharon E. , Fernandes Samuel B. , Mikel Mark A. , Bohn Martin O. , Lipka Alexander E. , Hirsch Candice N. 
Published: January 2023

AbstractUnderstanding how plants adapt to specific environmental changes and identifying genetic markers associated with phenotypic plasticity can help breeders develop plant varieties adapted to a rapidly changing climate. Here, we propose the use of marker effect networks as a novel method to identify markers associated with environmental adaptability. These marker effect networks are built by adapting commonly used software for building gene co-expression networks with marker effects across growth environments as the input data into the networks. To demonstrate the utility of these networks, we built networks from the marker effects of ∼10,000 non-redundant markers from 400 maize hybrids across nine environments. We demonstrate that networks can be generated using this approach, and that the markers that are co-varying are rarely in linkage disequilibrium, thus representing higher biological relevance. Multiple covarying marker modules associated with different weather factors throughout the growing season were identified within the marker effect networks. Finally, a factorial test of analysis parameters demonstrated marker effect networks are relatively robust to these options, with high overlap in modules associated with the same weather factors across analysis parameters. This novel application of network analysis provides unique insights into phenotypic plasticity, and specific environmental factors that modulate the genome.
Distinct neuroinflammatory signatures exist across genetic and sporadic ALS cohorts
Authors: Rifai Olivia M. , O’Shaughnessy Judi , Dando Owen R. , Munro Alison F. , Sewell Michael D.E. , Abrahams Sharon , Waldron Fergal M. , Sibley Christopher R. , Gregory Jenna M. 
Published: January 2023

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive loss of upper and lower motor neurons. ALS is on a pathogenetic disease spectrum with frontotemporal dementia (FTD), with patients sometimes experiencing elements of both conditions (ALS-FTSD). For mutations associated with ALS-FTSD, such as theC9orf72hexanucleotide repeat expansion (HRE), the factors influencing where an individual may lie on this spectrum require further characterisation. Here, using NanoString molecular barcoding with a panel of 770 neuroinflammatory genes, we interrogate inflammatory dysregulation at the level of gene expression. We identified 20 dysregulated neuroinflammatory genes in the motor cortex of deeply clinically phenotyped C9-ALSpost-mortemcases, with enrichment of microglial and inflammatory response gene sets. Our analyses also revealed two distinct ALS-related neuroinflammatory panel signatures (NPS), NPS1 and NPS2, delineated by the direction of expression of proinflammatory, axonal transport and synaptic signalling pathways. Two genes with significant correlations to available clinical metrics were selected for validation:FKBP5andBDNF. FKBP5 and its signalling partner, NF-κB, appeared to have a cell-type-specific staining distribution, with activated (i.e., nuclear) NF-κB immunoreactivity in C9-ALS. Expression ofBDNF, a correlate of disease duration, was confirmed to be higher in individuals with long compared to short disease duration using BaseScope™in situhybridisation. Finally, we compared NPS between C9-ALS cases and those from deeply clinically phenotyped sporadic ALS (sALS) and SOD1-ALS cohorts, with NPS1 and NPS2 appearing across all cohorts. A subset of these signatures was also detected in publicly available RNA-sequencing data from independent C9-ALS and sALS cohorts, underscoring the relevance of these pathways across cohorts. Our findings highlight the importance of tailoring therapeutic approaches based on distinct molecular signatures that exist between and within genetic and sporadic cohorts.
Development and characterization of new patient-derived xenograft (PDX) models of osteosarcoma with distinct metastatic capacities
Authors: Schott Courtney R. , Koehne Amanda L. , Sayles Leanne C. , Young Elizabeth P. , Luck Cuyler , Yu Katharine , Lee Alex G. , Breese Marcus R. , Leung Stanley G. , Xu Hang , Shah Avanthi Tayi , Liu Heng-Yi , Spillinger Aviv , Behroozfard Inge H. , Marini Kieren D. , Dinh Phuong T. , Pons Ventura María V. , Vanderboon Emma N. , Hazard Florette K. , Cho Soo-Jin , Avedian Raffi S. , Mohler David G. , Zimel Melissa , Wustrack Rosanna , Curtis Christina , Sirota Marina , Sweet-Cordero E. Alejandro 
Published: January 2023

AbstractModels to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology, especially for highly aggressive cancers with a propensity for metastatic spread. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, a large panel of models is needed to fully elucidate key aspects of disease biology and to recapitulate clinically-relevant phenotypes. We describe the development and characterization of osteosarcoma patient-derived xenografts (PDXs) and a panel of PDX-derived cell lines. Matched patient samples, PDXs, and PDX-derived cell lines were comprehensively evaluated using whole genome sequencing and RNA sequencing. PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication (WGD) in a subset of cell lines. These cell line models were heterogeneous in their metastatic capacity and their tissue tropism as observed in both intravenous and orthotopic models. As proof-of-concept study, we used one of these models to test the preclinical effectiveness of a CDK inhibitor on the growth of metastatic tumors in an orthotopic amputation model. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden in this model.Graphical Abstract
Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody
Authors: Kumar Sanjeev , Singh Swarandeep , Chatterjee Arnab , Bajpai Prashant , Sharma Shaifali , Katpara Sanket , Lodha Rakesh , Dutta Somnath , Luthra Kalpana 
Published: January 2023

SUMMARYThe structural and characteristic features of HIV-1 broadly neutralizing antibodies (bnAbs) from chronically infected pediatric donors are currently unknown. Herein, we characterized a heavy chain matured HIV-1 bnAb 44m, identified from a pediatric elite-neutralizer. Interestingly, in comparison to its wild-type AIIMS-P01 bnAb, 44m exhibited moderately higher level of somatic hypermutations of 15.2%. The 44m neutralized 79% of HIV-1 heterologous viruses (n=58) tested, with a geometric mean IC50titer of 0.36 µg/ml. The cryo-EM structure of 44m Fab in complex with fully-cleaved glycosylated native-like BG505.SOSIP.664.T332N gp140 envelope trimer at 4.4Å resolution revealed that 44m targets the V3-glycan N332-supersite and GDIR motif to neutralize HIV-1 with improved potency and breadth, plausibly attributed by a matured heavy chain as compared to that of wild-type AIIMS-P01. This study further improves our understanding on pediatric HIV-1 bnAbs and structural basis of broad HIV-1 neutralization by 44m may be useful blueprint for vaccine design in future.
Human skeletal muscle methylome after low carbohydrate energy balanced exercise
Authors: Gorski Piotr P. , Turner Daniel C. , Iraki Juma , Morton James P. , Sharples Adam P. , Areta José L. 
Published: January 2023

AbstractWe aimed to investigate the human skeletal muscle (SkM) DNA methylome after exercise in low carbohydrate (CHO) energy balance (with high fat) compared with exercise in low-CHO energy deficit (with low fat) conditions. The objective to identify novel epigenetically regulated genes and pathways associated with ‘train-low sleep-low’ paradigms. The sleep-low conditions included 9 males that cycled to deplete muscle glycogen while reaching a set energy expenditure. Post-exercise, low-CHO meals (protein-matched) completely replaced (using high-fat) or only partially replaced (low-fat) the energy expended. The following morning resting baseline biopsies were taken and the participants then undertook 75 minutes of cycling exercise, with skeletal muscle biopsies collected 30 minutes and 3.5 hours post exercise. Discovery of genome-wide DNA methylation was undertaken using Illumina EPIC arrays and targeted gene expression analysis was conducted by RT-qPCR. At baseline participants under energy balance (high fat) demonstrated a predominantly hypermethylated (60%) profile across the genome compared to energy deficit-low fat conditions. However, post exercise performed in energy balance (with high fat) elicited a more prominent hypomethylation signature 30 minutes post-exercise in gene regulatory regions important for transcription (CpG islands within promoter regions) compared with exercise in energy deficit (with low fat) conditions. Such hypomethylation was enriched within pathways related to: IL6-JAK-STAT signalling, metabolic processes, p53 / cell cycle and oxidative / fatty acid metabolism. Hypomethylation within the promoter regions of genes: HDAC2, MECR, IGF2 and c13orf16 were associated with significant increases in gene expression in the post-exercise period in energy balance compared with energy deficit. Furthermore, histone deacetylase, HDAC11 was oppositely regulated at the gene expression level compared with HDAC2, where HDAC11 was hypomethylated yet increased in energy deficit compared with energy balance conditions. Overall, we identify some novel epigenetically regulated genes associated with train-low sleep-low paradigms.
Propionate reinforces epithelial identity and reduces aggressiveness of non-small cell lung carcinoma via chromatin remodelling
Authors: Ramesh Vignesh , Gollavilli Paradesi Naidu , Pinna Luisa , Siddiqui Mohammad Aarif , Jakobsen Simon Toftholm , Boiteux Elisa Le , Olsen Karen Ege , Jensen Ole Nørregaard , Siersbæk Rasmus , Somyajit Kumar , Ceppi Paolo 
Published: January 2023

AbstractEpithelial to mesenchymal transition (EMT) is a developmental cellular program driving metastasis and chemo-resistance in cancer, but its pharmacological treatment has been so far challenging. Targeting deregulated metabolic processes in cancer is emerging as a realistic therapeutic strategy. Here, we used an EMT-focussed integrative functional genomic approach and identified negative association of the short-chain fatty acids propionate and butanoate with EMT in non-small cell lung cancer (NSCLC) patients. Strikingly, in vitro treatment of lung cancer cell lines with propionate reinforced the epithelial transcriptional program promoting cell adhesion and reverting the aggressive and chemoresistant EMT phenotype. Propionate treatment reduced cells metastatic ability in nude mice and limited lymph nodal spread in a genetic NSCLC mouse model. Further analyses indicated chromatin remodeling via H3K27 acetylation (p300-mediated) as the mechanism shifting the EMT balance towards epithelial state upon propionate. Propionate administration could be tested in the clinic for reducing NSCLC aggressiveness.HighlightsAn EMT-centric investigation of metabolic processes in a comprehensive lung cancer transcriptome profiles identified negative associations between EMT and SCFAs (propionate and butyrate)Propionate enhances the epithelial features both at the molecular and cellular levelsPre-treatment of cells with propionate inhibits EMT associated processes including migration and sensitizes the cells to chemotherapeutic drug cisplatinOral administration of propionate inhibits EMT-mediated lung colonization ability of NSCLC cells, and lymph node metastasis in a genetic mouse NSCLC modelMolecular mechanistic investigation of propionate revealed chromatin remodelling through p300-mediated histone acetylation in E-cadherin gene regulation along with epithelial features reinforcement