bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random Walk with Restart on multilayer networks: from node prioritisation to supervised link prediction and beyond
Authors: Baptista Anthony , Brière Galadriel , Baudot Anaïs 
Published: October 2023

AbstractBackgroundBiological networks have proven invaluable ability for representing biological knowledge. Multilayer networks, which gather different types of nodes and edges in multiplex, heterogeneous and bipartite networks, provide a natural way to integrate diverse and multi-scale data sources into a common framework. Recently, we developed MultiXrank, a Random Walk with Restart algorithm able to explore such multilayer networks. MultiXrank outputs scores reflecting the proximity between an initial set of seed node(s) and all the other nodes in the multilayer network. We illustrate here the versatility of bioinformatics tasks that can be performed using MultiXrank.ResultsWe first show that MultiXrank can be used to prioritise genes and drugs of interest by exploring multilayer networks containing interactions between genes, drugs, and diseases. In a second study, we illustrate how MultiXrank scores can also be used in a supervised strategy to train a binary classifier to predict gene-disease associations. The classifier performance are validated using outdated and novel gene-disease association for training and evaluation, respectively. Finally, we show that MultiXrank scores can be used to compute diffusion profiles and use them as disease signatures. We computed the diffusion profiles of more than 100 immune diseases using a multilayer network that includes cell-type specific genomic information. The clustering of the immune disease diffusion profiles reveals shared shared phenotypic characteristics.ConclusionOverall, we illustrate here diverse applications of MultiXrank to showcase its versatility. We expect that this can lead to further and broader bioinformatics applications.
The IRE1-bZIP60 branch of Unfolded Protein Response is required forArabidopsisimmune response toBotrytis cinerea
Authors: Cécile Blanchard , Sébastien Aimé , Amélie Ducloy , Siham Hichami , Marianne² Azzopardi , Jean-Luc Cacas , Olivier Lamotte 
Published: October 2023

AbstractThe Unfolded Protein Response (UPR) is a retrograde signalling pathway which is activated when endoplasmic reticulum (ER) proteostasis is disturbed. Here, we have investigated by reverse genetics the contribution of such pathway inArabidopsis thalianaresponse to two necrotrophic fungi of agricultural importance,Botrytis cinerea which is responsible for the development of grey mold disease, andAlternaria brassicicolawhich triggers black spot disease. We found that the branch of UPR dependent on the INOSITOL-REQUIRING ENZYME 1 (IRE1) and the transcription factor (TF) bZIP60 is required to restrict foliar necrotic symptoms induced by both fungi. Accordingly, focussing onB. cinerea, we provided evidence for the production of the active bZIP60 form during infection. This activation was accompanied by an increased expression of UPR-responsive genes coding for ER-localized chaperones and co-chaperones that belong to the ER-Quality Control (ER-QC) system. Furthermore, mutants deficient for two ER-QC components were also more susceptible to infection. By contrast, investigating the involvement of CELL DIVISION CYCLE 48 (CDC48) AAA+-ATPAses that assist ER-Associated Degradation (ERAD) pathway for disposal of luminal unfolded proteins, we showed that a series of mutants and transgenics are more resistant to grey mold disease. Seeking for molecular insights into how the ER could shape Arabidopsis immune response toB. cinerea, we quantified the expression of defence gene and cell death markers in singlebzip60and doubleire1mutants. However, none of those genes were mis-regulated in mutant genetic backgrounds, indicating that IRE1-bZIP60 branch of UPR modulates the Arabidopsis response toB. cinereaby a yet-to-be-identified mechanism. Interestingly, we identified the NAC053/NTL4 TF as a potential actor of this unknown mechanism, linking the UPR and proteasome stress regulon.Author summaryNecrotrophic fungi are one of the most economically significant plant pathogens worldwide, inflicting massive pre- and post-harvest losses on a wide range of fruit and vegetable crops. They adopt a necrotrophic lifestyle, deriving their nutrients predominantly from dead plant tissues to complete their life cycle.Botrytis cinereais the causal agent of grey mold and no plant shows complete resistance towards this pathogen. The use of genetic models such as the plantArabidopsis thalianahas partially enabled the understanding of the immunity mechanisms involved in the plant’s response toB. cinerea. Our work provides new insights into the cellular mechanisms of how plants cope with this pathogen. In this context, by means of a reverse genetic approach, we explored the role of the Unfolded Protein Response (UPR), a cell signalling pathway regulating protein homeostasis within the endoplasmic reticulum (ER) and thus protecting cells from a harmful over-accumulation of aberrant or misfolded proteins.
Allopolyploidization from two dioecious ancestors leads to recurrent evolution of sex chromosomes and reversion to autosomes
Authors: He Li , Wang Yuàn , Wang Yi , Zhang Ren-Gang , Wang Yuán , Hörandl Elvira , Mank Judith E. , Ming Ray 
Published: October 2023

AbstractPolyploidization presents an unusual challenge for species with sex chromosomes, as it can lead to complex combinations of sex chromosomes that disrupt reproductive development. This is particularly true for allopolyploidization between species with different sex chromosome systems. Here we assemble haplotype-resolved chromosome-level genomes of a female allotetraploid weeping willow (Salix babylonica) and a male diploidSalix dunniiusing Hi-C and PacBio HiFi reads. We use phylogenomics of nuclear and plastid genomes to show that weeping willow arose from crosses between female ancestor from theSalixclade, having XY sex chromosomes on chromosome 7, with a male ancestor from theVetrixclade, having ancestral XY sex chromosomes on chromosome 15. Our analysis reveals that weeping willow has one pair sex chromosomes, ZW on chromosome 15, that derive from the ancestral XY sex chromosomes in theVetrix-clade male ancestor, and the X chromosomes on chromosome 7 from theSalix-clade female ancestor has reverted to an autosome. Taken together, our results point to rapid evolution and reversion of sex chromosomes following allopolyploidization in weeping willow.Significance StatementWe assembled haplotype-resolved genomes and obtained gap-free sex chromosomes of a female allotetraploid weeping willow (Salix babylonica) and a male diploidSalix dunnii. The weeping willow arose from two dioecious ancestors, that have XY sex chromosomes on chromosome 7 and 15, respectively. The one pair sex chromosomes 15W and 15Z in weeping willow derived from ancestral 15X and 15Y, respectively. Inversions contributed to the evolutions of sex-linked regions (SLRs) of diploid and polyploid willows.
Pathophysiological Significance of Impaired KAT7-Dependent Histone H3K14 Acetylation During Zinc Deficiency
Authors: Fujisawa Takao , Takenaka Satoshi , Maekawa Lila , Kowada Toshiyuki , Matsui Toshitaka , Mizukami Shin , Kato Yugo , Suzuki Michio , Noma Hisashi , Naguro Isao , Ichijo Hidenori 
Published: October 2023

SummaryZinc is an indispensable micronutrient for optimal physiological functions, and zinc deficiency has been implicated in the pathogenesis of various human diseases. One potential mechanism underlying such pathogenic effects is the alteration of gene expression caused by zinc deficiency; however, the details of this process remain largely unexplored. Here, we show that during zinc deficiency, the histone acetyltransferase KAT7 loses its enzymatic activity, leading to the attenuated acetylation of histone H3 at Lys14 (H3K14ac) at enhancer regions. Physiologically, the decrease in H3K14ac leads to the upregulation of the expression of ZIP10, a plasma membrane-localized zinc transporter, thereby facilitating the import of extracellular zinc to maintain cellular zinc homeostasis. Moreover, prolonged zinc deficiency in mice induced by a zinc-deficient diet or high-fat diet, accompanied by decreased H3K14ac levels in the liver, upregulated the expression of genes associated with intracellular lipid droplet formation, leading to the accumulation of lipids within liver tissue. Our findings demonstrate that cells respond to zinc deficiency by converting it into an epigenetic signal that drives physiological or pathophysiological biological processes.
A specific innate immune response silences the virulence ofPseudomonas aeruginosain a latent infection model in theDrosophila melanogasterhost
Authors: Chen Jing , Lin Guiying , Ma Kaiyu , Li Zi , Liégeois Samuel , Ferrandon Dominique 
Published: October 2023

AbstractMicrobial pathogenicity often depends on the route of infection. For instance,P. aeruginosaorS. marcescenscause acute systemic infections when low numbers of bacteria are injected intoD. melanogasterflies whereas flies succumb much slower to the continuous ingestion of these pathogens, even though both manage to escape from the gut compartment and reach the hemocoel. Here, we have developed a latentP. aeruginosainfection model by feeding flies on the bacteria for a short period. The bacteria stably colonize internal tissues yet hardly cause any damage since latently-infected flies live almost as long as noninfected control flies. The apparently dormant bacteria display particular characteristics in terms of bacterial colony morphology, composition of the outer cell wall, and motility. The virulence of these bacteria can however be reactivated upon wounding the host. We show that melanization but not the cellular or the systemic humoral response is the predominant host defense that establishes latency and may coerce the bacteria to a dormant state. In addition, the lasting activation of the melanization responses in latently-infected flies provides a degree of protection to the host against a secondary fungal infection. Latent infections by an ingested pathogen protects against a variety of homologous or heterologous systemic secondary infectious challenges, a situation previously described for the endosymbiotic Wolbachia bacteria, a guard against viral infections.
Mathematical Preconditions for Existence of the Stock-Recruitment Function
Authors: Schaarschmidt Ute , Frank Anna S. J. , Subbey Sam 
Published: October 2023

AbstractFor marine species, several life stages link parents to their progeny (recruits), through a process referred to as recruitment. Current stock recruitment (SR) functions encapsulate this multi-stage relationship in a closed-form mathematical expression, which explicitly relates the biomass of parents, to the number of recruits. This functional relationship (between parents and recruits) is required for management purposes. No study, however, has investigated the conditions that validate the existence of the SR functions when all life history stages are incorporated into a model.In this study, we represent the processes leading to recruitment by a stage-and age-structured discrete-time population dynamic model. We show that in general, a SR function does not correctly represent the parent-progeny relationship. A valid relationship must incorporate information across the complete life cycle over several time periods. For populations with simple life cycle history, a functional relationship may result, which is not necessarily consistent with current SR functions.We present a brief discussion of the relevance of our results to effective management of fisheries.
Low-invasive sampling method for taxonomic for the identification of archaeological and paleontological bones by proteomics of their collagens
Authors: Fabrizi Isabelle , Flament Stéphanie , Delhon Claire , Gourichon Lionel , Vuillien Manon , Oueslati Tarek , Auguste Patrick , Rolando Christian , Bray Fabrice 
Published: October 2023

ABSTRACTCollagen from paleontological bones is an important organic material for isotopic measurement, radiocarbon and paleoproteomic analyzes, to provide information on diet, dating and taxonomy. Current paleoproteomics methods are destructive and require from a few milligrams to several tenths of milligrams of bone for analysis. In many cultures, bones are raw materials for artefact which are conserved in museum which hampers to damage these precious objects during sampling. Here, we describe a low-invasive sampling method that identifies collagen, taxonomy and post-translational modifications from Holocene and Upper Pleistocene bones dated to 130,000 and 150 BC using dermatological skin tape-discs for sampling. The sampled bone micro-powders were digested following our highly optimized eFASP protocol, then analyzed by MALDI FTICR MS and LC-MS/MS for identifying the genus taxa of the bones. We show that this low-invasive sampling does not deteriorate the bones and achieves results similar to those obtained by more destructive sampling. Moreover, this sampling method can be performed at archaeological sites or in museums.
Detecting the genetic variants associated with key culinary traits inDioscorea alata
Authors: Dossa Komivi , Houngbo Mahugnon Ezékiel , Lechaudel Mathieu , Malédon Erick , Zoclanclounon Yedomon Ange Bovys , Irep Jean-Luc , Nasir Mian Faisal , Chair Hâna , Cornet Denis 
Published: October 2023

AbstractQuality attributes play a pivotal role in determining consumers’ acceptability and market value of food crops.Dioscorea alatais a major yam species for food security in tropical areas, but our understanding of the genetic factors underlying tuber culinary traits is limited. This study aimed at elucidating the genetic basis of key culinary attributes, including dry matter content, cooking time, boiled yam hardness, and moldability, through genome-wide association studies (GWAS). Phenotypic assessments revealed notable variations among theD. alatagenotypes across two locations as well as significant correlations among the quality traits. The GWAS identified 25 significant associations distributed across 14 chromosomes. Allele segregation analysis of the identified loci highlighted favorable alleles associated with desired traits, such as reduced cooking time, increased dry matter content, enhanced hardness, and good moldability. Within the set of 42 putative candidate genes, we identified specific genes differentially expressed in tubers of distinct genotypes with contrasting quality attributes. Furthermore, we conducted a comparative analysis with previously reported quantitative trait loci for dry matter content and showed that multiple genomic regions govern this trait inD. alata. Our study offers valuable insights into the links between these key culinary traits and the underlying genetic basis inD. alata. These findings have practical implications for breeding programs aimed at enhancing the quality attributes of greater yam.
T-cell commitment inheritance – an agent-based multi-scale model
Authors: Andersson Emil , Rothenberg Ellen V. , Peterson Carsten , Olariu Victor 
Published: October 2023

ABSTRACTT-cell development provides an excellent model system for studying lineage commitment from a multipotent progenitor. The intrathymic development process has been thoroughly studied. The molecular circuitry controlling it has been dissected and the necessary steps like programmed shut off of progenitor genes and T-cell genes upregulation have been revealed. However, the exact timing between decision-making and commitment stage remains unexplored. To this end, we implemented an agent-based multi-scale model to investigate inheritance in early T-cell development. Treating each cell as an agent provides a powerful tool as it tracks each individual cell of a simulated T-cell colony, enabling the construction of lineage trees. Based on the lineage trees, we introduce the concept of the last common ancestors (LCA) of committed cells and analyse their relations, both at single-cell level and population level. In addition to simulating wild-type development, we also conduct knockdown analysis. Our simulations showed that the commitment is a three-step process over several cell generations where a cell is first prepared by a transcriptional switch. This is followed by the loss of the Bcl11b-opposing function two to three generations later which is when the decision to commit is taken. Finally, after another one to two generations, the cell becomes committed by transitioning to the DN2b state. Our results showed that there is inheritance in the commitment mechanism.
Deciphering circulating tumor cells binding in a microfluidic system thanks to a parameterized mathematical model
Authors: Ciavolella Giorgia , Granet Julien , Goetz Jacky G. , Osmani Naël , Etchegaray Christèle , Collin Annabelle 
Published: October 2023

AbstractThe spread of metastases is a crucial process in which some questions remain unanswered. In this work, we focus on tumor cells circulating in the bloodstream, the so-called Circulating Tumor Cells (CTCs). Our aim is to characterize their trajectories under the influence of hemodynamic and adhesion forces. We focus on already availablein vitromeasurements performed with a microfluidic device corresponding to the trajectories of CTCs – without or with different protein depletions – interacting with an endothelial layer. A key difficulty is the weak knowledge of the fluid velocity that has to be reconstructed. Our strategy combines a differential equation model – a Poiseuille model for the fluid velocity and an ODE system for the cell adhesion model – and a robust and well-designed calibration procedure. The parameterized model quantifies the strong influence of fluid velocity on adhesion and confirms the expected role of several proteins in the deceleration of CTCs. Finally, it enables the generation of synthetic cells, even for unobserved experimental conditions, opening the way to a digital twin for flowing cells with adhesion.
Genetic deficiency of ribosomal rescue factor HBS1L causes retinal dystrophy associated with Pelota and EDF1 depletion
Authors: Luo Shiyu , Alwattar Bilal , Li Qifei , Bora Kiran , Blomfield Alexandra K. , Lin Jasmine , Fulton Anne , Chen Jing , Agrawal Pankaj B. 
Published: October 2023

AbstractInherited retinal diseases (IRDs) encompass a genetically diverse group of conditions in which mutations in genes critical to retinal function lead to progressive loss of photoreceptor cells and subsequent visual impairment. A handful of ribosome-associated genes have been implicated in retinal disorders alongside neurological phenotypes. This study focuses on theHBS1Lgene, encoding HBS1 Like Translational GTPase which has been recognized as a critical ribosomal rescue factor. Previously, we have reported a female child carrying biallelicHBS1Lmutations, manifesting growth restriction, developmental delay, and hypotonia. In this study, we describe her ophthalmologic findings, compare them with theHbs1ltm1a/tm1ahypomorph mouse model, and evaluate the underlying microscopic and molecular perturbations. The patient was noted to have impaired visual function observed by electroretinogram (ERG), with dampened amplitudes of a- and b-waves in both rod- and cone-mediated responses.Hbs1ltm1a/tm1amice exhibited profound retinal thinning of the entire retina, specifically of the outer retinal photoreceptor layer, detected using in vivo imaging of optical coherence tomography (OCT) and retinal cross sections. TUNEL assay revealed retinal degeneration due to extensive photoreceptor cell apoptosis. Loss of HBS1L resulted in comprehensive proteomic alterations in mass spectrometry analysis, with169 proteins increased and 480 proteins decreased including many critical IRD-related proteins. GO biological process and GSEA analyses reveal that these downregulated proteins are primarily involved in photoreceptor cell development, cilium assembly, phototransduction, and aerobic respiration. Furthermore, apart from the diminished level of PELO, a known partner protein, HBS1L depletion was accompanied by reduction in translation machinery associated 7 homolog (Tma7), and Endothelial differentiation-related factor 1(Edf1) proteins, the latter of which coordinates cellular responses to ribosome collisions. This novel connection between HBS1L and ribosome collision sensor (EDF1) further highlights the intricate mechanisms underpinning ribosomal rescue and quality control that are essential to maintain homeostasis of key proteins of retinal health, such as rhodopsin.
Nutritional sex-specificity on bacterial metabolites during mosquito development leads to adult sex-ratio distortion
Authors: Romoli Ottavia , Serrato-Salas Javier , Gapp Chloé , Epelboin Yanouk , Figueras Ivern Pol , Barras Frédéric , Gendrin Mathilde 
Published: October 2023

AbstractMosquitoes rely on their microbiota for B vitamin synthesis. We previously found thatAedes aegyptithird-instar larvae cleared of their microbiota were impaired in their development, notably due to a lack of folic acid (vitamin B9). In this study, we found that diet supplementation using a cocktail of seven B vitamins did not improve mosquito developmental success, but rather had a significant impact on the sex-ratio of the resulting adults, with an enrichment of female mosquitoes emerging from B vitamin-treated larvae. A transcriptomic analysis of male and female larvae identified some sex-specific regulated genes upon vitamin treatment. When treating germ-free larvae with individual B vitamins, we detected a specific toxic effect related to biotin (vitamin B7) exposure at high concentrations. We then provided germ-free larvae with varying biotin doses and showed that males are sensitive to biotin toxicity at a lower concentration than females. Gnotobiotic larvae exposed to controlled low bacterial counts or with bacteria characterized by slower growth, show a male-enriched adult population, suggesting that males require less bacteria-derived nutrients than females. These findings shed new light on sex-specific nutritional requirements and toxicity thresholds during the development of insect larvae, which impact the sex ratio of adults.
Tumor-infiltrating nerves functionally alter brain circuits and modulate behavior in a mouse model of head-and-neck cancer
Authors: Barr Jeffrey , Walz Austin , Restaino Anthony C. , Amit Moran , Barclay Sarah M. , Vichaya Elisabeth G. , Spanos William C. , Dantzer Robert , Talbot Sebastien , Vermeer Paola D. 
Published: October 2023

AbstractCancer patients often experience changes in mental health, prompting an exploration into whether nerves infiltrating tumors contribute to these alterations by impacting brain functions. Using a mouse model for head and neck cancer and neuronal tracing we show that tumor-infiltrating nerves connect to distinct brain areas. The activation of this neuronal circuitry altered behaviors (decreased nest-building, increased latency to eat a cookie, and reduced wheel running). Tumor-infiltrating nociceptor neurons exhibited heightened calcium activity and brain regions receiving these neural projections showed elevated Fos as well as increased calcium responses compared to non-tumor-bearing counterparts.The genetic elimination of nociceptor neurons decreased brain Fos expression and mitigated the behavioral alterations induced by the presence of the tumor. While analgesic treatment restored nesting and cookie test behaviors, it did not fully restore voluntary wheel running indicating that pain is not the exclusive driver of such behavioral shifts. Unraveling the interaction between the tumor, infiltrating nerves, and the brain is pivotal to developing targeted interventions to alleviate the mental health burdens associated with cancer.Significance StatementHead and neck cancers are infiltrated by sensory nerves which connect to a pre-existing circuit that includes areas in the brain. Neurons within this circuit are altered and mediate modifications in behavior.