bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome wide inherited modifications of the tomato epigenome by trans-activated bacterial CG methyltransferase
Authors: Pavan Kumar Bapatla Kesava , Beaubiat Sébastien , Yadav Chandra Bhan , Eshed Ravit , Arazi Tzahi , Sherman Amir , Bouché Nicolas 
Published: April 2024

ABSTRACTEpigenetic variation is mediated by epigenetic marks such as DNA methylation occurring in all cytosine contexts in plants. CG methylation plays a critical role in silencing transposable elements and regulating gene expression. The establishment of CG methylation occurs via the RNA-directed DNA methylation pathway and CG methylation maintenance relies on METHYLTRANSFERASE1, the homologue of the mammalian DNMT1. Here, we examined the capacity to stably alter the tomato genome methylome by a bacterial CG-specificM.SssImethyltransferase expressed through the LhG4/pOP transactivation system. Methylome analysis ofM.SssIexpressing plants revealed that their euchromatic genome regions are specifically hypermethylated in the CG context, and so are most of their genes. However, changes in gene expression were observed only with a set of genes exhibiting a greater susceptibility to CG hypermethylation near their transcription start site. Unlike gene rich genomic regions, our analysis revealed that heterochromatic regions are slightly hypomethylated at CGs only. Notably, someM.SssI-induced hypermethylation persisted even without the methylase or transgenes, indicating inheritable epigenetic modification. Collectively our findings suggest that heterologous expression ofM.SssIcan create new inherited epigenetic variations and changes in the methylation profiles on a genome wide scale. This open avenues for the conception of epigenetic recombinant inbred line populations with the potential to unveil agriculturally valuable tomato epialleles.
FGF2 binds to the allosteric site (site 2) and activates αvβ3 integrin and FGF1 binds to site 2 but suppresses integrin activation by FGF2: a potential mechanism of anti-inflammatory action of FGF1
Authors: Takada Yoko K , Wu Xueson , Wei David , Hwang Samuel , Takada Yoshikazu 
Published: April 2024

AbstractFGF1 is known as an anti-inflammatory and has suppresses insulin resistance. Its homologue FGF2 is pro-inflammatory. Mechanism of FGF1’s anti-inflammatory action and FGF2’s pro-inflammatory action are unknown. Several inflammatory cytokines (e.g., CX3CL1, CCL5, and CXCL12, and CD40L) bind to the classical ligand (RGD)-binding site (site 1) of integrin αvβ3. In addition, they bind to the allosteric site (site 2) of αvβ3, which is distinct from site 1, and allosterically activate αvβ3. Site 2 is involved in inflammatory signals since inflammatory lipid mediator 5-hydroxycholesterol binds to site 2 and induces integrin activation and inflammatory signals (e.g., TNF and IL-6 secretion). We thus hypothesized that FGF1 and FGF2 bind to site 2 and affect activation status of integrins. Here we describe that FGF2 bound to site 2 and allosterically activated αvβ3 integrin. Point mutations in the site 2-binding interface of FGF2 suppressed this activation, indicating that FGF2 binding to site 2 is required for inducing integrin activation. In contrast, FGF1 bound to site 2 but did not activate αvβ3, and instead suppressed integrin activation induced by FGF2, indicating that FGF1 acts as an antagonist of site 2. These findings suggest that FGF1’s anti-inflammatory action is mediated by blocking site 2. FGF1 has potential as an anti-inflammatory agent, but is not appropriate for long-term use since it is potent mitogen. A non-mitogenic FGF1 mutant (R50E), which is defective in binding to site 1 of αvβ3, suppressed αvβ3 activation by FGF2 as effectively as WT FGF1. We propose that FGF1 R50E has therapeutic potential for inflammatory diseases.
Molecular basis of proton-sensing by G protein-coupled receptors
Authors: Howard Matthew K. , Hoppe Nicholas , Huang Xi-Ping , Macdonald Christian B. , Mehrota Eshan , Rockefeller Grimes Patrick , Zahm Adam , Trinidad Donovan D. , English Justin , Coyote-Maestas Willow , Manglik Aashish 
Published: April 2024

AbstractThree proton-sensing G protein-coupled receptors (GPCRs), GPR4, GPR65, and GPR68, respond to changes in extracellular pH to regulate diverse physiology and are implicated in a wide range of diseases. A central challenge in determining how protons activate these receptors is identifying the set of residues that bind protons. Here, we determine structures of each receptor to understand the spatial arrangement of putative proton sensing residues in the active state. With a newly developed deep mutational scanning approach, we determined the functional importance of every residue in proton activation for GPR68 by generating ∼9,500 mutants and measuring effects on signaling and surface expression. This unbiased screen revealed that, unlike other proton-sensitive cell surface channels and receptors, no single site is critical for proton recognition in GPR68. Instead, a network of titratable residues extend from the extracellular surface to the transmembrane region and converge on canonical class A GPCR activation motifs to activate proton-sensing GPCRs. More broadly, our approach integrating structure and unbiased functional interrogation defines a new framework for understanding the rich complexity of GPCR signaling.One-sentence summaryThe protonation networks governing activation of human pH-sensing GPCRs are uncovered by integrative cryo-EM and deep mutational scanning.
Effect of different odors on the rat urine proteome
Authors: Liu Yuqing , Wang Haitong , Gao Youhe 
Published: April 2024

AbstractDo rats have corresponding changes in their urinary proteome when smelling different odors? In this study, urine samples were collected from six rats after smelling sesame oil and essential balm for three days. And samples were collected before and on the third and fourth days. Comparing the urinary protein groups of Day0 and Day4 of the sesame oil group, 143 differential proteins were identified, and the average number of randomly generated differential proteins was 7.3, which means that about 95% of the differential proteins could not be randomly generated. in the sesame oil group, differential proteins such as low-density lipoprotein receptor-related protein 2 and fetuin B, a biomarker of COPD, which are associated with olfaction, were identified. While uteroglobulin, trichothecene factor 3, and visfatin 2 were identified in the essential balm group, which had significant changes and were related to the production of olfactory sensation. It is noteworthy that we identified odor-binding protein 2A in the essential balm group, which was present in the e-cigarette model. This study demonstrates that odor can affect rat urinary proteome, with different odors affecting it differently. This provides a new approach to explore the biological process of olfaction.
Bactogram: Spatial Analysis of Bacterial Colonization in Epidermal Wounds
Authors: Wallblom Karl , Forsberg Fredrik , Lundgren Sigrid , Fisher Jane , Cardoso José , Petruk Ganna , Strömdahl Ann-Charlotte , Saleh Karim , Puthia Manoj , Schmidtchen Artur 
Published: April 2024

AbstractSkin barrier damage and subsequent development of harmful microbiota contribute to conditions such as wound infections, atopic dermatitis, and chronic wounds, which impact millions of people globally and pose a significant economic burden on healthcare systems. Established microbial sampling methods, such as swabs and tissue biopsies, provide limited information on the spatial distribution of bacteria. We here describe a new method that produces a visual map of the distribution of cultivable bacteria, denoted “Bactogram”, across the whole wound and surrounding skin, suitable for image-based quantification. As part of an exploratory endpoint in a clinical trial (NCT05378997) we applied the Bactogram method to 48 suction blister wounds in 24 healthy volunteers. Bacteria developed in all wounds, predominantly on the skin under the dressing and near wound edges. Two quantification methods, based on visual scoring and image analysis, demonstrated high inter-, and intra-rater agreement and were used to characterize bacterial re-colonization during epidermal wound healing. We also demonstrated proof of concept that the method can be used with chromogenic agar to enable spatial identification of pathogenic bacterial species, such asStaphylococcus aureus. In conclusion, this study introduces a simple method for sampling bacteria over large areas and generating a bacterial map that can identify spatial variations in bacterial composition and abundance in skin and wound conditions.
BOADICEA model: updates to theBRCA2breast cancer risks for ages 60 years and older
Authors: Ficorella Lorenzo , Yang Xin , Easton Douglas F , Antoniou Antonis C 
Published: April 2024

AbstractBreast cancer risks in olderBRCA2pathogenic variant carriers are understudied. Recent studies show a marked decline in the relative risk at older ages. We used data from two large studies to update the breast cancer risks in the BOADICEA model forBRCA2carriers 60 years and older.
Cognitive training reshapes functional lateralization of fronto-parietal network in patients with vascular cognitive impairment no dementia
Authors: Jin Xinhu , Xing Yi , Lyu Baihan , Wang Xiuyi , Tang Yi , Du Yi 
Published: April 2024

AbstractBackground and ObjectivesVascular cognitive impairment no dementia represents cognitive deficits due to vascular causes but falls short of a dementia diagnosis. Cognitive training has emerged as a safe and effective intervention for vascular cognitive impairment no dementia, though its underlying mechanisms remain obscure. This study investigates how subcortical vascular cognitive impairment no dementia and computerized cognitive training affect a brain fundamental organization feature named functional lateralization.MethodsIn a randomized, active-controlled trial, patients with subcortical vascular cognitive impairment no dementia were divided into training and control groups, and underwent neuropsychological assessments and resting-state functional magnetic resonance imaging at baseline, end of 7-week intervention, and 6-month follow-up. Additionally, a healthy older group provided baseline data. Two types of functional lateralization indices (LIs) were defined based on resting-state functional connectivity: LI of intrahemispheric functional connectivity (LI_intra) which represents the left-right difference of functional connectivity strength within the same hemisphere, and LI of interhemispheric heterotopic functional connectivity (LI_he) which represents the left-right difference of functional connectivity strength across bilateral hemispheres.ResultsInitially, patients (28 in training group and 28 in control group) showed a fronto-parietal network lateralization pattern akin to healthy older adults (N = 26). However, enhanced right-lateralized LI_he was associated with better memory solely in healthy adults. After the intervention, only the training group exhibited a reduction in LI_he in the fronto-parietal network, indicating a lateralization shift towards bilateral network connectivity. This shift, especially towards leftward lateralization, was linked with improved executive and memory functions in the training group. Notably, these changes disappeared at the 6-month follow-up.DiscussionThese findings suggest that subcortical vascular cognitive impairment no dementia modifies the relationship between fronto-parietal network lateralization and cognitive function, rather than altering the lateralization pattern itself. Through hemispherical reorganizing and balancing of the fronto-parietal network, short-term computerized cognitive training facilitates executive and memory functions by leveraging functional compensation by reorganization. This study illuminates the neural plasticity induced by cognitive training in vascular cognitive impairment no dementia, highlighting its potential to transform cognitive outcomes by tapping into the brain’s capacity for reorganization and adaptation.Trial registrationThe trial was registered underClinicalTrials.gov(NCT02640716) and conducted under both CONSORT statement and CONSORT statement for nonpharmacological interventions.
Mapping Global Research Trends in Digital Occupational Health: A Bibliometric Analysis Utilizing the Scopus Database
Authors: Er-Rays Youssef , M’dioud Meriem , Lemqeddem Hamid Ait 
Published: April 2024

AbstractThe 2019 health crisis has underscored the imperative role of information and communications technology (ICT) in bolstering employees’ health, well-being, and ameliorating health risks associated with artificial intelligence (AI) errors. Digital health technology facilitates remote healthcare delivery, employee health monitoring, and enhanced communication channels between workers and healthcare professionals. This paper conducts a comprehensive analysis of global trends in digital occupational health research over the past decade, with a specific focus on prolific authors, countries, academic institutions, and publications. Leveraging the PRISMA framework and VOSviewer software, relevant documents are extracted from the Scopus database. The findings underscore the significance of digital technology in the realm of occupational health and highlight the pressing need for further investigation, particularly encompassing emerging economies and employing robust methodologies to ensure the reliability of results. This study offers a valuable assessment of advancements in digital occupational health, serving as a foundation for future research endeavors aimed at optimizing workplace health and well-being on a global scale.
Re-defining how mRNA degradation is coordinated with transcription and translation in bacteria
Authors: Kim Seunghyeon , Wang Yu-Huan , Hassan Albur , Kim Sangjin 
Published: April 2024

AbstractIn eukaryotic cells, transcription, translation, and mRNA degradation occur in distinct subcellular regions. How these mRNA processes are organized in bacteria, without employing membrane-bound compartments, remains unclear. Here, we present generalizable principles underlying coordination between these processes in bacteria. InEscherichia coli, we found that co-transcriptional degradation is rare for mRNAs except for those encoding inner membrane proteins, due to membrane localization of the main ribonuclease, RNase E. We further found, by varying ribosome binding sequences, that translation affects mRNA stability not because ribosomes protect mRNA from degradation, but because low translation leads to premature transcription termination in the absence of transcription-translation coupling. Extending our analyses toBacillus subtilisandCaulobacter crescentus, we established subcellular localization of RNase E (or its homolog) and premature transcription termination in the absence of transcription-translation coupling as key determinants that explain differences in transcriptional and translational coupling to mRNA degradation across genes and species.
Decoupled genetic and epigenetic variation in the montane endemicErodium cazorlanum(Geraniaceae) and a widespread congener
Authors: Martín-Blázquez Rubén , Medrano Mónica , Bazaga Pilar , Balao Francisco , Paun Ovidiu , Alonso Conchita 
Published: April 2024

AbstractEpigenetic states offer an additional layer of variation besides genetic polymorphism that contribute to phenotypic variation and may arise either randomly or in response to environmental factors. We hypothesize that closely related species with different life-histories and habitat requirements could show distinct patterns of intraspecific epigenetic variation. We used Restriction-site Associated DNA sequencing (RADseq) and its bisulfite-converted variant (bsRADseq) to investigate in Sierra de Cazorla (SE Spain) the genetic and epigenetic population structure of two congeneric species, the endemic woody perennialErodium cazorlanumand the widely distributed annual herbE. cicutarium. Population genomics analyses revealed no structure in eitherE. cazorlanumandE. cicutarium,suggesting substantial gene flow between the study populations. In contrast, we found that the mean proportion of global DNA methylation was different between populations and species, withE. cazorlanumDNA showing higher methylation average and across-individuals variation. For each species, we searched for the loci with the strongest epigenetic differentiation between populations (differentially methylated cytosines, DMCs), and summarized them across regions (differentially methylated regions, DMRs). Multivariate analysis and hierarchical clustering of single cytosines’ methylation percentages did not group individuals by population, pointing to high epigenetic variation within populations. DMRs were enriched inCopiatransposable elements, putatively associated with stress response in plants. Our results suggest that variation at both genetic and epigenetic levels in our study area occur mainly within natural populations ofE. cazorlanumandE. cicutarium,with stronger population structure inE. cicutarium,and highlight the relevance of analyzing short distance spatial patterns.
Early-life scarcity adversity biases behavioral development toward a bipolar-like phenotype in mice heterozygous for CNTNAP2
Authors: Chelini Gabriele , Fortunato-Asquini Tommaso , Cerilli Enrica , Monsorno Katia , Catena Benedetta , Dall’O’ Ginevra Matilde , Paolicelli Rosa Chiara , Bozzi Yuri 
Published: April 2024

AbstractThe etiological complexity of psychiatric disorders arises from the dynamic interplay between genetic and environmental vulnerabilities. Among the environmental components, early-life adversities (ELA) are a major risk-factors for developing a psychiatric disorder. Yet, the mechanistic interaction between ELA and genetic vulnerability contributing to psychopathology is poorly understood. To fill this gap, we took advantage of the ideally controlled conditions of a pre-clinical approach. In this study we raised a mouse model with genetic predisposition to multiple psychiatric disorders (autism spectrum, schizophrenia, bipolar disorder), theCntnap2+/-mouse, with limited bedding and nesting (LBN), a well-established paradigm to induce early-life stress in rodents. These mice were compared to LBN-raisedCntnap2+/+littermates, as well as parallel groups ofCntnap2+/+andCntnap2+/-raised in standard conditions. Using a battery for behavioral phenotyping we show that ELA shapes non-overlapping phenotypic landscapes based on genetic predisposition. Specifically, we found that LBN-raisedCntnap2+/-mice develop a perseverative risk-taking behavior in the elevated plus maze and that this behavior is highly predictive of their success in the social interaction, assessed with the 3-chamber test. This finding suggests that the intrusion of anxiety into the social behavioral domain contributes to extreme gain- or loss-of function in social interaction, resembling a bipolar-like phenotype. Finally, we show that LBN promotes synaptic hypertrophy in the basolateral nucleus of the amygdala, but only inCntnap2+/-raised in LBN this condition was found in combination with microglia abnormalities. We conclude that the interplay between ELA andCntnap2haploinsufficiency exacerbates bipolar-like behaviors in mice, and that this may be consequence of deficient synaptic homeostasis in the basolateral amygdala.
Excitation Spillover from PSII to PSI Measured in Leaves at 77K
Authors: Terashima Ichiro , Oguchi Riichi , Atsuzawa Kimie , Kaneko Yasuko , Kono Masaru 
Published: April 2024

ABSTRACTHeterogeneous distribution of PSI and PSII in thick grana in shade chloroplasts is argued to hinder spillover of chlorophyll excitations from PSII to PSI. To examine this dogma, we measured fluorescence induction at 77K at 690 nm (PSII) and 760 nm (mainly PSI) in the leaf discs ofSpinacia oleracea,Cucumis sativusand shade tolerantAlocasia odora, grown at high and low light, and quantified their spillover capacities. PSI fluorescence (FI) consists of the intrinsic PSI fluorescence (FIα) and fluorescence caused by excitations spilt over from PSII (FIβ). WhenFIand FII parameters between State 1 and State 2, induced by weak far-red and blue light, were compared, PSII maximum fluorescence (FIIm) andFIβwere greater, andFIαwas smaller in State 1 and thereby the spillover ratio,FIβ/(FIα+FIβ) orFIβ/FIm, was greater in State 1. Since the leftoverFIImwas found to be about 10% of totalFmat 760 nm, all the data were corrected. Even after the correction, the spillover ratio inFImin State 1 ranged from 21 to 32%, and the spillover ratios were comparable irrespective of growth light conditions. Although extensive grana in low light grown plants would suggest that PSII and PSI are too separated for spillover, inA. odorachloroplasts, the ratio of non-appressed thylakoid membranes/total thylakoid membranes was little affected by growth light and more than 40%. Abundant non-appressed thylakoids would contribute to efficient spillover.
Rules of engagement for condensins and cohesins guide mitotic chromosome formation
Authors: Samejima Kumiko , Gibcus Johan H. , Abraham Sameer , Cisneros-Soberanis Fernanda , Samejima Itaru , Beckett Alison J. , Pučeková Nina , Abad Maria Alba , Medina-Pritchard Bethan , Paulson James R. , Xie Linfeng , Jeyaprakash A. Arockia , Prior Ian A. , Mirny Leonid A. , Dekker Job , Goloborodko Anton , Earnshaw William C. 
Published: April 2024

AbstractDuring mitosis, interphase chromatin is rapidly converted into rod-shaped mitotic chromosomes. Using Hi-C, imaging, proteomics and polymer modeling, we determine how the activity and interplay between loop-extruding SMC motors accomplishes this dramatic transition. Our work reveals rules of engagement for SMC complexes that are critical for allowing cells to refold interphase chromatin into mitotic chromosomes. We find that condensin disassembles interphase chromatin loop organization by evicting or displacing extrusive cohesin. In contrast, condensin bypasses cohesive cohesins, thereby maintaining sister chromatid cohesion while separating the sisters. Studies of mitotic chromosomes formed by cohesin, condensin II and condensin I alone or in combination allow us to develop new models of mitotic chromosome conformation. In these models, loops are consecutive and not overlapping, implying that condensins do not freely pass one another but stall upon encountering each other. The dynamics of Hi-C interactions and chromosome morphology reveal that during prophase loops are extruded in vivo at ∼1-3 kb/sec by condensins as they form a disordered discontinuous helical scaffold within individual chromatids.