bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refining type and timing of measured crop variables for the calibration of a new winter wheat cultivar in the STICS crop model
Authors: Gawinowski Meije , Aubry Maël , Buis Samuel , Garcia Cécile , Deswarte Jean-Charles , Bancal Marie-Odile , Launay Marie 
Published: February 2025

AbstractCrop models need to be regularly upgraded with parametrization for new cultivars but this requires calibration, which is a major challenge. With winter wheat cultivar Rubisko as a case study, we propose to apply a calibration protocol to estimate the parameters of this new cultivar with multi-trials experimental data. We tested the calibration protocol in different conditions including or not LAI and/or biomass experimental data and we found that the resulting LAI and biomass dynamics strongly diverge. Several key findings emerge from this study: (1) RUE parameters should be excluded from the calibration process, as their critical role in biomass dynamics causes the optimization algorithm to treat them as adjustment parameters, resulting in unrealistic values for multiple parameters; (2) either LAI or biomass variables alone are sufficient for calibration, enabling experimental efforts to focus on one variable rather than both; and (3) the use of a synthetic dataset has facilitated the identification of the optimal type and timing of data collection needed to parameterize a new variety in the model. Moreover, the proposed methodology offers extrapolatable solutions applicable to other contexts (e.g., different models or datasets) and provides guidance on acquiring the most effective dataset for optimal calibration. The unbalanced structure of our dataset also highlighted the need to mobilize other calibration criteria (weighted RMSE) and alternative solutions to bridge the gap between quantitative metrics and empirical visual assessments.
RAB23loss-of-function mutation causes context-dependent ciliopathy in Carpenter syndrome
Authors: Leong WY , Tung WL , Chui WH , Wilkie Andrew O M , Hor CHH 
Published: February 2025

AbstractThe primary cilium is a signal transduction organelle whose dysfunction clinically causes ciliopathies in humans. RAB23 is a small GTPase known to regulate the Hedgehog signalling pathway and ciliary trafficking. Mutations ofRAB23in humans lead to Carpenter syndrome (CS), an autosomal recessive disorder clinically characterized by craniosynostosis, polysyndactyly, skeletal defects, obesity, and intellectual disability. Although the clinical features of CS bear some resemblance to those of ciliopathies, the exact relationship between the pathological manifestations of CS and the ciliary function ofRAB23remains ambiguous. Besides, thein vivociliary functions ofRAB23remain poorly characterised.Here, we demonstratein vivoandin vitro Rab23loss-of-function mutants modelling CS, includingRab23conditional knockout (CKO) mouse mutants, CS patient-derived induced pluripotent stem cells (iPSCs), and zebrafish morphants. TheRab23-CKO mutants exhibit multiple developmental and phenotypical traits recapitulating the clinical features of human ciliopathies and CS, indicating a causal link between the loss ofRab23and ciliopathy. In line with the ciliopathy-like phenotypes, all three different vertebrate mutant models consistently show a perturbation of primary cilia formation, intriguingly, in a context-dependent manner.In vivoexamination of primary cilia inRab23-CKO mutants reveals profound cell-type specific ciliary abnormalities in chondrocytes and neocortical neurons, but not in epithelial cells, cerebellar granule cells and hippocampus neurons. A profound reduction in ciliation frequency and/or shortening of primary cilia was observed in the neurons and neural progenitor cells derived from CS patient iPSCs. Furthermore,Rab23-KO neural progenitor cells were desensitized to primary cilium-dependent activation of the Hedgehog signaling pathway. Collectively, these findings indicate that the absence ofRAB23causes dysfunctional primary cilia in a cell-type distinctive manner, which underlies the pathological manifestations of CS. Our findings present the firstin vivoevidence validating the unique context-specific function ofRAB23in the primary cilium. Through the use of patient-derived iPSCs differentiated cells, we present direct evidence of primary cilia anomalies in CS, thereby confirming CS as a ciliopathy disorder.
Dietary manipulation of intestinal microbes prolongs survival in a mouse model of Hirschsprung disease
Authors: Tjaden Naomi E. Butler , Liou Megan J. , Sax Sophie E. , Lassoued Nejia , Lou Meng , Schneider Sabine , Beigel Katherine , Eisenberg Joshua D. , Loeffler Emma , Anderson Sierra E. , Yan Guang , Litichevskiy Lev , Dohnalová Lenka , Zhu Yixuan , Jin Daniela Min Jing Che , Raab Jessica , Furth Emma E. , Thompson Zachary , Rubenstein Ronald C. , Pilon Nicolas , Thaiss Christoph A. , Heuckeroth Robert O. 
Published: February 2025

SummaryEnterocolitis is a common and potentially deadly manifestation of Hirschsprung disease (HSCR) but disease mechanisms remain poorly defined. Unexpectedly, we discovered that diet can dramatically affect the lifespan of a HSCR mouse model (Piebald lethal,sl/sl) where affected animals die from HAEC complications. In thesl/slmodel, diet alters gut microbes and metabolites, leading to changes in colon epithelial gene expression and epithelial oxygen levels known to influence colitis severity. Our findings demonstrate unrecognized similarity between HAEC and other types of colitis and suggest dietary manipulation could be a valuable therapeutic strategy for people with HSCR.AbstractHirschsprung disease (HSCR) is a birth defect where enteric nervous system (ENS) is absent from distal bowel. Bowel lacking ENS fails to relax, causing partial obstruction. Affected children often have “Hirschsprung disease associated enterocolitis” (HAEC), which predisposes to sepsis. We discovered survival ofPiebald lethal(sl/sl) mice, a well-established HSCR model with HAEC, is markedly altered by two distinct standard chow diets. A “Protective” diet increased fecal butyrate/isobutyrate and enhanced production of gut epithelial antimicrobial peptides in proximal colon. In contrast, “Detrimental” diet-fedsl/slhad abnormal appearing distal colon epithelium mitochondria, reduced epithelial mRNA involved in oxidative phosphorylation, and elevated epithelial oxygen that fostered growth of inflammation-associatedEnterobacteriaceae. Accordingly, selective depletion ofEnterobacteriaceaewith sodium tungstate prolongedsl/slsurvival. Our results provide the first strong evidence that diet modifies survival in a HSCR mouse model, without altering length of distal colon lacking ENS.HighlightsTwo different standard mouse diets alter survival in thePiebald lethal(sl/sl) mouse model of Hirschsprung disease, without impacting extent of distal colon aganglionosis (the region lacking ENS).Piebald lethalmice fed the “Detrimental” diet had many changes in colon epithelial transcriptome including decreased mRNA for antimicrobial peptides and genes involved in oxidative phosphorylation. Detrimental diet fedsl/slalso had aberrant-appearing mitochondria in distal colon epithelium, with elevated epithelial oxygen that drives lethalEnterobacteriaceaeovergrowth via aerobic respiration.Elimination ofEnterobacteriaceaewith antibiotics or sodium tungstate improves survival ofPiebald lethalfed the “Detrimental diet”.Graphical abstract
Non-target effects on the soil microbiome of a plant root exudate biocontrol for Fusarium wilt
Authors: Torres-Bedoya Eliana , Studholme David J. , Warmington Rachel , Bebber Daniel P. 
Published: February 2025

AbstractCrop rotation and intercropping withAlliumspp. (e.g. garlic, onion) are recognized as biological controls of Fusarium wilt in several crops. However, the non-target effects of this strategy on the soil microbiome are largely unknown. We evaluated the effect of cultivatingMusa basjoo,Allium tuberosum(Chinese leek), and their co-cultivation on the rhizosphere and bulk soil microbiome under glasshouse conditions. We do not report the impact of Chinese leek on Foc abundances, as this has been previously reported. The bacterial and fungal communities in the rhizosphere and bulk soil varied depending on the plant type. The microbiomes of allium and bananas were consistently dissimilar, and the co-cultivation treatment contained constituent taxa from both. However, the effect of allium on soil community composition was outweighed by that of bananas in the co-cultivation scenario. Discriminative taxa for allium included members of the generaSphingomonas, Microbacterium, Flavihumibacter, Brevundimonas, Pseudolabrys, Ramlibacter, Trichoderma, MortierellaandFusarium. In the case of bananas, predominant biomarkers encompassed members ofRhizobacter, Noviherbaspirillum, Pseudarthrobacter, Aquabacterium, Pseudomonas, TausoniaandHumicolaBiomarkers and predictions of functional gene abundances suggest that shifts in the soil microbiome induced by allium are correlated with increases in microorganisms exhibiting potential disease suppression and antibiotic or antifungal traits, whereas those in bananas are associated with plant-growth-promoting microorganisms. The biocontrol efficacy of allium co-cultivation may there involve shifts in the soil microbiome as well as direct impacts of root exudate chemistry onFusariumplant pathogens.
Persistent Disruptions in Prefrontal Connectivity Despite Behavioral Rescue by Environmental Enrichment in a Mouse Model of Rett Syndrome
Authors: Ährlund-Richter Sofie , Harpe Jonathan , Fernandes Giselle , Lam Ruby , Sur Mriganka 
Published: February 2025

ABSTRACTRett Syndrome, a neurodevelopmental disorder caused by loss-of-function mutations in theMECP2gene, is characterized by severe motor, cognitive and emotional impairments. Some of the deficits may result from changes in cortical connections, especially downstream projections of the prefrontal cortex, which may also be targets of restoration following rearing conditions such as environmental enrichment that alleviate specific symptoms. Here, using a heterozygousMecp2+/−female mouse model closely analogous to human Rett Syndrome, we investigated the impact of early environmental enrichment on behavioral deficits and prefrontal cortex connectivity. Behavioral analyses revealed that enriched housing rescued fine motor deficits and reduced anxiety, with enrichment-housedMecp2+/−mice performing comparably to wild-type (WT) controls in rotarod and open field assays. Anatomical mapping of top-down anterior cingulate cortex (ACA) projections demonstrated altered prefrontal cortex connectivity inMecp2+/−mice, with increased axonal density in the somatosensory cortex and decreased density in the motor cortex compared to WT controls. ACA axons revealed shifts in hemispheric distribution, particularly in the medial network regions, withMecp2+/−mice exhibiting reduced ipsilateral dominance. These changes were unaffected by enriched housing, suggesting that structural abnormalities in prefrontal cortex connectivity persist despite behavioral improvements. Enriched housing rescued brain-derived neurotrophic factor (BDNF) levels in the hippocampus but failed to restore BDNF levels in the prefrontal cortex, consistent with the persistent deficits observed in prefrontal axonal projections. These findings highlight the focal nature of changes induced by reduction of MeCP2 and by exposure to environmental enrichment, and suggest that environmental enrichment starting in adolescence can alleviate behavioral deficits without reversing abnormalities in large-scale cortical connectivity.
Neurons in the inferior colliculus use multiplexing to encode features of frequency-modulated sweeps
Authors: Drotos Audrey C. , Wajdi Sarah Z. , Malina Michael , Silveira Marina A. , Williamson Ross S. , Roberts Michael T. 
Published: February 2025

AbstractWithin the central auditory pathway, the inferior colliculus (IC) is a critical integration center for ascending sound information. Previous studies have shown that many IC neurons exhibit receptive fields for individual features of auditory stimuli, such as sound frequency, intensity, and location, but growing evidence suggests that some IC neurons may multiplex features of sound. Here, we used in vivo juxtacellular recordings in awake, head-fixed mice to examine how IC neurons responded to frequency-modulated sweeps that varied in speed, direction, intensity, and frequency range. We then applied machine learning methods to determine how individual IC neurons encode features of FM sweeps. We found that individual IC neurons multiplex FM sweep features using various strategies including spike timing, distribution of inter-spike intervals, and first spike latency. In addition, we found that decoding accuracy for sweep direction can vary with sweep speed and frequency range, suggesting the presence of mixed selectivity in single neurons. Accordingly, using static receptive fields for direction alone yielded poor predictions of neuron responses to vocalizations that contain simple frequency changes. Lastly, we showed that encoding strategies varied across individual neurons, resulting in a highly informative population response for FM sweep features. Together, our results suggest that multiplexing sound features is a common mechanism used by IC neurons to represent complex sounds.
Molecularly-guided spatial proteomics captures single-cell identity and heterogeneity of the nervous system
Authors: Dutta Sayan , Pang Marion , Coughlin Gerard M. , Gudavalli Sirisha , Roukes Michael L. , Chou Tsui-Fen , Gradinaru Viviana 
Published: February 2025

AbstractSingle-cell proteomics is an emerging field with significant potential to characterize heterogeneity within biological tissues. It offers complementary insights to single-cell transcriptomics by revealing unbiased proteomic changes downstream of the transcriptome. Recent advancements have focused on enhancing proteome coverage and depth, mostly in cultured cell lines, and a few recent studies have explored the potential of analyzing tissue micro-samples but were limited to homogenous peripheral tissues. In this current work, we utilize the power of spatial single cell-proteomics through immunostaining-guided laser capture microdissection (LCM) coupled with LC-MS to investigate the heterogenous central nervous system. We used this method to compare neuronal populations from cortex and substantia nigra, two brain regions associated with motor and cognitive function and various neurological disorders. Moreover, we used the technique to understand the neuroimmune changes associated with stab wound injury. Finally, we focus our application on the peripheral nervous system, where we compare the proteome of the myenteric plexus cell ganglion to the nerve bundle. This study demonstrates the utility of spatial single-cell proteomics in neuroscience research toward understanding fundamental biology and the molecular drivers of neurological conditions.
A cluster of RNA Polymerase II molecules is stably associated with an active gene
Authors: Mukherjee Apratim , Kapoor Manya , Shankta Kareena , Fallacaro Samantha , Carter Raymond D. , Ratchasanmuang Puttachai , Haloush Yara I. , Mir Mustafa 
Published: February 2025

AbstractIn eukaryotic nuclei, transcription is associated with discrete foci of RNA Polymerase II (RNAPII) molecules. How these clusters interact with genes and their impact on transcriptional activity remain heavily debated. Here we take advantage of the naturally occurring increase in transcriptional activity during Zygotic Genome Activation (ZGA) inDrosophila melanogasterembryos to characterize the functional roles of RNAPII clusters in a developmental context. Using single-molecule tracking and lattice light-sheet microscopy, we find that RNAPII cluster formation depends on transcription initiation and that cluster lifetimes are reduced upon transcription elongation. We show that single clusters are stably associated with active gene loci during transcription and that cluster intensities are strongly correlated with transcriptional output. Our data suggest that prior to ZGA, RNAPII clusters prime genes for activation, whereas after ZGA, clusters are composed mostly of elongating molecules at individual genes.
Duplications in the Chlorophyllaoxygenase (CAO) gene across the Viridiplantae
Authors: Poirier Mackenzie C. , Wright Roberta , Cvetkovska Marina 
Published: February 2025

AbstractViridiplantae, a diverse group of green plants and alga that have evolved from a common ancestor, are unified in their ability to produce and use two types of chlorophyll (chlorophyllaand chlorophyllb) to capture light energy. In addition to its role in light harvesting, appropriate levels of chlorophyllbare required for accumulation, assembly, and stability of light harvesting complexes within the photosynthetic apparatus. Chlorophyllbis synthesized from chlorophyllaby the enzyme chlorophyllideaoxygenase (CAO), a Rieske-type mononuclear non-heme iron oxygenase. A regulatory degron sequence, described in detail only in land plants, has been demonstrated to regulate the stability of CAO proteins based on the availability of chlorophyllb. Recent identification of CAO gene duplication in bryophyte and green algal species, combined with expanded availability of sequenced genomes within the Viridiplantae, prompted further investigation into the role of gene duplication in the evolution of chlorophyllbbiosynthesis. Examination of genomes from 246 plant and algae species revealed independently occurring CAO duplications throughout the Viridiplantae, with a higher prevalence of duplication in land plants compared to their algal relatives. Additionally, we demonstrate that the degron sequence is absent in in chlorophytes, but first appears as a conserved sequence in charophytes, and is very highly conserved among the embryophytes. The evolutionary history of CAO throughout the Viridiplantae lineage is discussed based on these key observations, adding to our understanding of chlorophyllbbiosynthesis and the role of CAO in photosynthetic species.
TRPV4 Dominates High Shear-Induced Initial Traction Response and Long-Term Relaxation Over Piezo1
Authors: Chandurkar Mohanish K. , Yang Manli , Rostami Majid , Han Sangyoon J. 
Published: February 2025

AbstractModulation of endothelial traction is critical for the responses of endothelial cells to fluid shear stress (FSS), which has profound implications for vascular health and atherosclerosis. Previously, we demonstrated that under high FSS, endothelial cells rapidly increase traction forces, followed by relaxation, with traction aligning in the flow direction. In contrast, low shear preconditioning induces a modest short-term increase in traction (<30 min), followed by a secondary long-term (>14 hr) rise, with traction/cells aligning perpendicular to the flow. The upstream mechanosensors driving these responses, however, remain unknown. Here, we sought the roles of Piezo1 and TRPV4 ion channels in shear-induced traction modulation. We report that HUVECs with Piezo1 silencing reduced the initial traction rise in half under high FSS compared to those by WT cells, while not affecting the traction modulation in response to low FSS or traction/cell alignment to the flow direction. Conversely, cells with siTRPV4 fully abrogated the initial traction rise, as well as alignment of traction and cells, in response to both high and low FSS conditions. Dual inhibition of Piezo1 and TRPV4 further impaired both initial and long-term traction under high FSS. Interestingly, dual-inhibited cells displayed larger initial traction responses to low FSS compared to control cells, suggesting the involvement of alternative calcium-independent pathways that become dominant when both ion channels are nonfunctional. Additionally, either ion channel inhibition led to secondary long-term traction increase even under high FSS condition. These findings suggest that while both Piezo1 and TRPV4 channels contribute to shear mechanotransduction, TRPV4 plays more dominant role than Piezo1 in mediating the initial traction rise and sustaining long-term relaxation under high or low shear stress, highlighting their critical and distinct contributions to endothelial mechanotransduction and remodeling.
Seeing what you hear: sound intensity alters rat visual perception in a temporal frequency classification task
Authors: Zanzi Mattia , Rinaldi Francesco Guido , Fornasaro Silene , Piasini Eugenio , Zoccolan Davide 
Published: February 2025

AbstractWhile integration of multimodal sensory stimuli in cortical hierarchies is well studied, the functional impact of hetero-modal inputs on visual perception is less explored. Here we use a visual classification task in rats to investigate how task-irrelevant sounds modify visual processing. Sound intensity, but not temporal congruency with visual stimuli, effectively compresses the task’s visual perceptual space, suggesting inhibition as a mediator of auditory-visual interactions in neural representations.
Platsafeguards maternally aged oocytes against programmed cell death through activating the Erk1/2 pathway
Authors: He Xingsi , Zhang Hanwen , Wang Ya , Yan Huanyu , Chen Qiuzhen , Su Min , Shi Qiaozhen , Zeng Xiao , Sheng Wei , Wang Yangmin , Wang Chikun , Hou Shuyue , Hu Zhibin , He Yuanlin , Wang Xi 
Published: February 2025

ABSTRACTThe decline in oocytes quality and developmental potential with female reproductive aging is well recognized, yet the underlying mechanisms remain insufficiently investigated. In this study, through an integrative analysis of transcriptomes and morphologies of individual oocytes from young and aged mice, morphologically defective aged oocytes are identified with distinct transcriptomic features. Further analysis demonstrates that both apoptotic and ferroptotic pathways are activated in the defective aged oocytes, and simultaneously blocking both pathways reverses the defective morphology to the largest extent. ThePlatgene, which encodes tissue-type plasminogen activator (tPA), is downregulated with oocyte aging, andPlatknockdown increases oocytes susceptibility to both apoptosis and ferroptosis. Mechanistically, tPA functions as an upstream signaling molecule for Erk1/2 activation by interacting with particular phosphorylation kinases such as Alk. Consequently,Platloss downregulates Erk1/2 pathway activity in oocytes, leading to degeneration through programmed cell death. Supplementing exogenous tPA inin vitrooocyte maturation cultures reduces defect rate of aged oocytes, thereby improving oocyte quality and developmental potential. Collectively,Platplays a pivotal role in protecting aged mouse oocytes from programmed cell death, and tPA supplementation may serve as a potential clinical strategy to enhance oocyte quality in females of advanced maternal age.
Non-Gaussian statistics of nanohertz stochastic gravitational waves
Authors: Xue Xiao , Pan Zhen , Dai Liang 
Published: February 2025

Multiple pulsar timing arrays (PTAs) have recently reported evidence for nHz stochastic gravitational wave background (SGWB), stimulating intensive discussions about its physical origin. In principle, the sources may be either supermassive black hole binaries (SMBHBs) or processes in the early Universe. One key difference between the two lies in the statistics of the SGWB frequency power spectrum. In particular, the often assumed Gaussian random SGWB does not accurately describe the distribution of the collective SMBHB emission. This work presents a semianalytical framework for calculating the non-Gaussian statistics of SGWB power expected from SMBHBs. We find that (a) wave interference between individual SMBHBs with indistinguishable observed frequencies and (b) the Poisson fluctuation of the source numbers, together shape the non-Gaussian statistics. Implementing the non-Gaussian statistics developed in this work, we investigate the sensitivity of current and future PTA datasets in distinguishing the origin of the SGWB through non-Gaussian information. Additionally, we find an interesting approximation of the non-Gaussian statistics, which has implications for accurately and practically treating non-Gaussianity in PTA Bayesian analyses.

Published by the American Physical Society
2025