bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGF9, a potent mitogen, is a new ligand for integrin αvβ3, and the FGF9 mutant defective in integrin binding acts as an antagonist
Authors: Chang Chih-Chieh , Takada Yoko K , Cheng Chao-Wen , Maekawa Yukina , Mori Seiji , Takada Yoshikazu 
Published: December 2023

AbstractFGF9 is a potent mitogen and survival factor, but FGF9 protein level is generally low and restricted to a few adult organs. Aberrant expression of FGF9 usually results in cancer. However, the mechanism of FGF9 action has not been fully established. Previous studies showed that FGF1 and FGF2 directly bind to integrin αvβ3 and this interaction is critical for signaling functions (FGF-integrin crosstalk). FGF1 and FGF2 mutants defective in integrin binding were defective in signaling, whereas the mutants still bound to FGFR, and suppressed angiogenesis and tumor growth, indicating that they act as antagonists. We hypothesize that FGF9 requires direct integrin binding for signaling. Here we show that docking simulation of interaction between FGF9 and αvβ3 predicted that FGF9 binds to the classical ligand-binding site of αvβ3. We showed that FGF9 actually bound to integrin αvβ3, and generated an FGF9 mutants in the predicted integrin-binding interface. An FGF9 mutant (R108E) was defective in integrin binding, activating FRS2α and ERK1/2, inducing DNA synthesis, cancer cell migration, and invasion in vitro. R108E suppressed DNA synthesis induced by WT FGF9 and suppressed DNA synthesis and activation of FRS2α and ERK1/2 induced by WT FGF9 (dominant-negative effect). These findings indicate that FGF9 requires direct integrin binding for signaling and that R108E has potential as an antagonist to FGF9 signaling.
Role of Immature Choroid Plexus in the Pathology of Autism Spectrum Disorder
Authors: Tanabe Motoi , Saito Yuga , Takasaki Ayaka , Nakano Keita , Suzuki Chikako , Kawamura Nao , Hattori Aki , Nagashima Shun , Oikawa Mami , Yanagi Shigeru , Yamaguchi Tomoyuki , Fukuda Toshifumi 
Published: December 2023

SUMMARYDuring gestation, the choroid plexus (ChP) produces protein-rich cerebrospinal fluid and matures prior to brain development. It is assumed that ChP dysfunction has a profound effect on developmental neuropsychiatric disorders, such as Autism Spectrum Disorder (ASD). However, the mechanisms linking immature ChP to the onset of ASD remain unclear. In this study, we found that ChP-specific CAMDI-knockout mice developed an immature ChP, alongside decreased multiciliogenesis and expression of differentiation marker genes following disruption of the cerebrospinal fluid barrier. These mice exhibited ASD-like behaviors, including impaired socialization with delayed critical period. Additionally, administration of Metformin, an FDA-approved drug, before the critical period achieved ChP maturation and restored social behaviors. Furthermore, ASD model mice and ASD patient-derived organoids developed immature ChP. These results indicate towards involvement of immature ChP in the pathogenesis of ASD and suggest the targeting of functional maturation of ChP as a therapeutic strategy for ASD.
Identification of parthenogenesis-inducing effector proteins inWolbachia
Authors: Fricke Laura C , Lindsey Amelia RI 
Published: December 2023

ABSTRACTBacteria in the genusWolbachiahave evolved numerous strategies to manipulate arthropod sex, including the conversion of would-be male offspring to asexually reproducing females. This so-called “parthenogenesis-induction” phenotype can be found in a number ofWolbachiastrains that infect arthropods with haplodiploid sex determination systems, including parasitoid wasps. Despite the discovery of microbe-mediated parthenogenesis more than 30 years ago, the underlying genetic mechanisms have remained elusive. We used a suite of genomic, computational, and molecular tools to identify and characterize two proteins that are uniquely found in parthenogenesis-inducingWolbachiaand have strong signatures of host-associated bacterial effector proteins. These putative parthenogenesis-inducing proteins have structural homology to eukaryotic protein domains including nucleoporins, the key insect sex-determining factor Transformer, and a eukaryotic-like serine-threonine kinase with leucine rich repeats. Furthermore, these proteins significantly impact eukaryotic cell biology in the model,Saccharomyces cerevisiae. We suggest these proteins are parthenogenesis-inducing factors and our results indicate this would be made possible by a novel mechanism of bacterial-host interaction.
The Lateral/Caudal Ganglionic Eminence Makes a Limited Contribution to Cortical Oligodendrocytes
Authors: Li Jialin , Yang Feihong , Tian Yu , Wang Ziwu , Qi Dashi , Yang Zhengang , Song Jiangang , Ding Jing , Wang Xin , Zhang Zhuangzhi 
Published: December 2023

AbstractThe emergence of myelinating oligodendrocytes represents a pivotal developmental milestone in vertebrates, given their capacity to ensheath axons and facilitate the swift conduction of action potentials. It is widely accepted that cortical oligodendrocyte progenitor cells (OPCs) arise from medial ganglionic eminence (MGE), lateral/caudal ganglionic eminence (LGE/CGE) and cortical radial glial cells (RGCs). Here, we used two different fate mapping strategies to challenge the established notion that the LGE generates cortical OPCs. Furthermore, we used a Cre/loxP-dependent exclusion strategy to reveal that the LGE/CGE-derived OPCs are minimal. Additionally, we showed that specifically eliminating MGE-derived OPCs leads to a significant reduction of cortical OPCs. Together, our findings indicate that the contribution of OPCs from LGE/CGE is minimal, contrary to previous beliefs. These findings provide a new view of the developmental origins of cortical OPCs and a valuable foundation for future research on both normal development and oligodendrocyte-related disease.
Quantitative Analysis of Autophagy in Single Cells: Differential Response to Amino Acid and Glucose Starvation
Authors: Martin Katie R. , Celano Stephanie L. , Sheldon Ryan D. , Jones Russell G. , MacKeigan Jeffrey P. 
Published: December 2023

ABSTRACTAutophagy is a highly conserved, intracellular recycling process by which cytoplasmic contents are degraded in the lysosome. This process occurs at a low level constitutively; however, it is induced robustly in response to stressors, in particular, starvation of critical nutrients such as amino acids and glucose. That said, the relative contribution of these inputs is ambiguous and many starvation medias are poorly defined or devoid of multiple nutrients. Here, we sought to generate a quantitative catalog of autophagy across multiple stages and in single, living cells under normal growth conditions as well as in media starved specifically of amino acids or glucose. We found that autophagy is induced by starvation of amino acids, but not glucose, in U2OS cells, and that MTORC1-mediated ULK1 regulation and autophagy are tightly linked to amino acid levels. While autophagy is engaged immediately during amino acid starvation, a heightened response occurs during a period marked by transcriptional upregulation of autophagy genes during sustained starvation. Finally, we demonstrated that cells immediately return to their initial, low-autophagy state when nutrients are restored, highlighting the dynamic relationship between autophagy and environmental conditions. In addition to sharing our findings here, we provide our data as a high-quality resource for others interested in mathematical modeling or otherwise exploring autophagy in individual cells across a population.
CpG Island Definition and Methylation Mapping of the T2T-YAO Genome
Authors: Xiao Ming , Wei Rui , Yu Jun , Gao Chujie , Yang Fengyi , Zhang Le 
Published: December 2023

AbstractPrecisely defining and mapping all cytosine positions and their clusters, known as CpG islands (CGIs), as well as their methylation status are pivotal for genome-wide epigenetic studies, especially when population-centric reference genomes are ready for timely application. Here we first align the two high-quality reference genomes, T2T-YAO and T2T-CHM13, from different ethnic backgrounds in a base-by-base fashion and compute their genome-wide density-defined and position-defined CGIs. Second, mapping some representative genome-wide methylation data from selected organs onto the two genomes, we find that there are about 4.7–5.8% sequence divergency of variable categories depending on quality cutoffs. Genes among the divergent sequences are mostly associated with neurological functions. Moreover, CGIs associated with the divergent sequences are significantly different with respect to CpG density and observed CpG/expected CpG (O/E) ratio between the two genomes. Finally, we find that the T2T-YAO genome not only has a greater CpG site coverage than that of the T2T-CHM13 genome when whole-genome bisulfite sequencing (WGBS) data from the European and American populations are mapped to each reference, but also show more hyper-methylated CpG sites as compared to the T2T-CHM13 genome. Our study suggests that future genome-wide epigenetic studies of the Chinese populations rely on both acquisition of high-quality methylation data and subsequent precision CGI mapping based on the Chinese T2T reference.
Genomic plasticity is a blueprint of diversity inSalmonellalineages
Authors: Kushwaha Simran Krishnakant , Anand Abhirath , Wu Yi , Ávila Hugo Leonardo , Sicheritz-Pontén Thomas , Millard Andrew , Marathe Sandhya Amol , Nobrega Franklin L. 
Published: December 2023

AbstractThe flexible genome, organised in regions of genomic plasticity (RGP), serves as a potent facilitator of the dynamic evolution of bacterial genomes through gene acquisition and loss. Here we explored the genomic plasticity acrossSalmonellalineages, revealing a purposeful, non-random integration pattern of pathogenicity-related gene clusters into specific RGP. Noteworthy examples include the correlation between the type I-E CRISPR-Cas system, gold tolerance, and specific RGP. The scattered prevalence of RGP acrossSalmonellalineages profoundly shapes the pathogenicity makeup ofSalmonellastrains. The preferences of RGP seem guided by conserved flanking genes that likely share regulatory and functional coordination. For example, metal resistance genes are predominant in RGP positioned near stress resistance genes, indicating a regulatory network to efficiently counter stressors. Additionally, we observed that different plasmid incompatibility types and prophage genera carry distinct pathogenicity genes. Similar to RGP, their distribution acrossSalmonellalineages plays a critical role in defining pathogenicity. By uncovering these intricate connections among gene clusters, RGP, mobile genetic elements, and pathogenic attributes, our study offers novel insights into the evolutionary trajectory ofSalmonellaand holds promise for predicting future adaptations and developing targeted interventions against infections.
Paracrine effects of the senescence-associated secretory phenotype decrease cancer cell adhesion
Authors: Cole Aidan R. , Buj Raquel , Elhaw Amal Taher , Uboveja Apoorva , Tangudu Naveen , Oesterreich Steffi , Stallaert Wayne , Hempel Nadine , Aird Katherine M. 
Published: December 2023

ABSTRACTHigh grade serous ovarian cancer (HGSOC) is the most lethal gynecological cancer. Platinumbased therapies such as cisplatin are standard-of-care for HGSOC patients; however, the majority of HGSOCs initially treated with cisplatin will recur with widespread disseminated disease. Cisplatin induces cellular senescence, a stable cell cycle arrest. Although they are non-proliferative, senescent cells secrete a complex mix of cytokines and small molecules, named the senescence associated secretory phenotype (SASP), that have been shown to have pro-tumorigenic effects. To investigate how the SASP contributes to HGSOC progression, we used conditioned media from cisplatin therapy-induced senescent cells to culture naïve HGSOC spheroids. We report that while the SASP does not affect spheroid formation, the adhesion of cells within spheroids is altered, leading to cell detachment from spheroids. Interestingly, our data indicate that this occurs in an MMP-independent manner. Analysis of RNA-Seq samples indicates many adhesion-related genes and adhesion factors are transcriptionally downregulated by the SASP, particularly fibronectin and integrins, which was validated by immunofluorescence in spheroids. These data reveal that senescent cells contribute to a transcriptional program in nearby cancer cells in a paracrine fashion that decreases their adhesion, which may contribute to tumor dissemination.
A red light-induced genetic system for control of extracellular electron transfer
Authors: Zhao Fengjie , Niman Christina M. , Ostovar Ghazaleh , Chavez Marko S. , Atkinson Joshua T. , Bonis Benjamin M. , Gralnick Jeffrey A. , El-Naggar Mohamed Y. , Boedicker James Q. 
Published: December 2023

AbstractOptogenetics is a powerful tool for spatiotemporal control of gene expression. Several light-inducible gene regulators have been developed to function in bacteria, and these regulatory circuits have been ported into new host strains. Here, we developed and adapted a red light-inducible transcription factor forShewanella oneidensis. This regulatory circuit is based on the iLight optogenetic system, which controls gene expression using red light. Promoter engineering and a thermodynamic model were used to adapt this system to achieve differential gene expression in light and dark conditions within aS. oneidensishost strain. We further improved the iLight optogenetic system by adding a repressor to invert the genetic circuit and activate gene expression under red light illumination. The inverted iLight genetic circuit was used to control extracellular electron transfer (EET) withinS. oneidensis. The ability to use both red and blue light-induced optogenetic circuits simultaneously was demonstrated. Our work expands the synthetic biology toolbox ofShewanella, which could facilitate future advances in applications with electrogenic bacteria.
Multi-omics framework to reveal the molecular determinants of fermentation performance in wine yeast populations
Authors: de Celis Miguel , Ruiz Javier , Benitez-Dominguez Belen , Vicente Javier , Tomasi Sandra , Izquierdo-Gea Sergio , Rozés Nicolás , Ruiz-de-Vila Candela , Gombau Jordi , Zamora Fernando , Barroso Alicia , Terron-Camero Laura C. , Andres-Leon Eduardo , Santos Antonio , Belda Ignacio 
Published: December 2023

AbstractBackgroundConnecting the composition and function of industrial microbiomes is a major aspiration in microbial biotechnology. Here, we address this question in wine fermentation, a model system where the diversity and functioning of fermenting yeast species is determinant of the flavor and quality of the resulting wines.ResultsFirst, we surveyed yeast communities associated with grape musts collected across wine appellations, revealing the importance of environmental (i.e., biogeography) and anthropic factors (i.e., farming system) in shaping community composition and structure. Then, we assayed the fermenting yeast communities in synthetic grape must under common winemaking conditions. The dominating yeast species defines the fermentation performance and metabolite profile of the resulting wines, and it is determined by the initial fungal community composition rather than the imposed fermentation conditions. Yeast dominance also had a more pronounced impact on wine meta-transcriptome than fermentation conditions. We unveiled yeast-specific transcriptomic profiles, leveraging different molecular functioning strategies in wine fermentation environments. We further studied the orthologs responsible for metabolite production, revealing modules associated with the dominance of specific yeast species. This emphasizes the unique contributions of yeast species to wine flavor, here summarized in an array of orthologs that defines the individual contribution of yeast species to wine ecosystem functioning.ConclusionsOur study bridges the gap between yeast community composition and wine metabolite production, providing insights to harness diverse yeast functionalities with the final aim to producing tailored high-quality wines.
Histone marks enable formation of immiscible phase-separated chromatin compartments
Authors: Sun Wenjing , Wang Jiacheng , Liu Wenqian , Tang Baixue , Qu Hongyuan , Wang Jianwei , Li Haitao , Xie Wei , Li Pilong 
Published: December 2023

AbstractEukaryotic chromatin is organized into compartments for gene expression regulation, but the underlying mechanisms remain unclear. Here, we demonstrate that multivalent H3K27me3 and its reader, CBX7-PRC1 complex, regulate facultative heterochromatin via a phase separation mechanism, similar to constitutive heterochromatin1. Facultative and constitutive heterochromatin represent distinct, coexisting condensates in nuclei.In vitro,H3K27me3- and H3K9me3-marked nucleosomal arrays and their reader complexes can phase separate into immiscible condensates that are analogous to the relationship between facultative and constitutive heterochromatinin vivo. Moreover, overexpression of CBX7-PRC1 causes aberrant chromatin compartmentalizationin vivoas demonstrated by H3K9me3 CUT&Tag and up-regulation of genes related to cancer such as acute myeloblastic leukemia (AML). CBX7 inhibitor effectively inhibits cancer cell proliferation possibly through phase separation-mediated compartment reorganization. Our data demonstrated how the specificity of compartmentalization is achieved based on the formation of immiscible phase-separated condensates, and offer novel epigenetic mechanistic insights into tumor development.
CLUH maintains functional mitochondria and translation in motoneuronal axons and prevents peripheral neuropathy
Authors: Zaninello Marta , Schlegel Tim , Nolte Hendrik , Pirzada Mujeeb , Savino Elisa , Barth Esther , Wüstenberg Hauke , Uddin Tesmin , Wolff Lisa , Wirth Brunhilde , Lehmann Helmar C. , Cioni Jean-Michel , Langer Thomas , Rugarli Elena I. 
Published: December 2023

AbstractTransport and local translation of mRNAs in distal axonal compartments are essential for neuronal viability. Local synthesis of nuclear-encoded mitochondrial proteins protects mitochondria from damage during their long journey along the axon, however the regulatory factors involved are largely unknown. Here, we show that CLUH, a cytosolic protein that binds mRNAs encoding mitochondrial proteins, is essential for preventing axonal degeneration of spinal motoneurons and maintaining motor behavior in the mouse. We demonstrate that CLUH is enriched in the growth cone of developing spinal motoneurons and is required for their growth. The absence of CLUH affects the abundance of target mRNAs and the corresponding mitochondrial proteins more prominently in axons, leading to ATP deficits specifically in the growth cone. CLUH binds ribosomal subunits, translation initiation and ribosome recycling components, and preserves axonal translation. Overexpression of the ribosome recycling factor ABCE1 rescues the growth cone and translation defects in CLUH-deficient motoneurons. In conclusion, we demonstrate a role for CLUH in mitochondrial quality control and translational regulation in axons, which are essential for their development and long-term integrity and function.
Small-molecule activators of a bacterial signaling pathway inhibit virulence
Authors: Mansour Kathryn E. , Qi Yunchuan , Yan Mingdi , Ramström Olof , Priebe Gregory P. , Schaefers Matthew M. 
Published: December 2023

AbstractTheBurkholderiagenus encompasses multiple human pathogens, including potential bioterrorism agents, that are often extensively antibiotic resistant. The FixLJ pathway inBurkholderiais a two-component system that regulates virulence. Previous work showed thatfixLJmutations arising during chronic infection confer increased virulence while decreasing the activity of the FixLJ pathway. We hypothesized that small-molecule activators of the FixLJ pathway could serve as anti-virulence therapies. Here, we developed a high-throughput assay that screened over 28,000 compounds and identified 11 that could specifically active the FixLJ pathway. Eight of these compounds, denotedBurkholderiaFixActivator (BFA) 1-8, inhibited the intracellular survival ofBurkholderiain THP-1-dervived macrophages in afixLJ-dependent manner without significant toxicity. One of the compounds, BFA1, inhibited the intracellular survival in macrophages of multipleBurkholderiaspecies. Predictive modeling of the interaction of BFA1 withBurkholderiaFixL suggests that BFA1 binds to the putative ATP/ADP binding pocket in the kinase domain, indicating a potential mechanism for pathway activation. These results indicate that small-molecule FixLJ pathway activators are promising anti-virulence agents forBurkholderiaand define a new paradigm for antibacterial therapeutic discovery.
Selective Vulnerability of Parvocellular Oxytocin Neurons in Social Dysfunction
Authors: Tsurutani Masafumi , Goto Teppei , Hagihara Mitsue , Irie Satsuki , Miyamichi Kazunari 
Published: December 2023

AbstractSelective vulnerability offers a conceptual framework for understanding neurodegenerative disorders, such as Parkinson’s disease, where specific neuronal types are selectively affected while adjacent ones are spared. The applicability of this framework to neurodevelopmental disorders remains uncertain, particularly those characterized by atypical social behaviors such as autism spectrum disorder. Here, employing a single-cell transcriptome analysis in mice, we show that an embryonic disturbance known to induce social dysfunction preferentially impairs gene expressions crucial for neural functions in parvocellular oxytocin (OT) neurons—a subtype linked to social rewards—while neighboring cell types experience a lesser impact. Chemogenetic stimulation of OT neurons at the neonatal stage ameliorated social deficits in early adulthood, concurrent with a cell-type-specific sustained recovery of the pivotal gene expressions within parvocellular OT neurons. Collectively, our data shed light on the transcriptomic selective vulnerability within the hypothalamic social behavioral center and provide a potential therapeutic target through specific neonatal neurostimulation.
Do peers really influence doctors' knowledge contribution behavior? Evidence from online health communities
Authors: Lei Licai , Hu Shiyi 
Published: December 2023

PurposeThe online health community's success depends on doctors' active participation, so it is essential to understand the factors that affect doctors' knowledge contribution behavior in the online health communities. From the perspective of peer effect, this paper discusses the influence of focal doctors' peers on focal doctors' knowledge contribution behavior and the mechanism behind it. This paper aims to solve these problems.Design/methodology/approachEmpirical data of 1,938 doctors were collected from a Chinese online health community, and propensity score matching and ordinary least squares were employed to verify the proposed theoretical model.FindingsThe results show that the presence of focal doctors' peers in online health communities has a positive effect on the knowledge contribution behavior of focal doctors, and the economic returns and social returns of focal doctors' peers have a significant mediating effect.Originality/valueThis paper discusses focal doctors' knowledge contribution behavior from the perspective of peer effect. It enhances the understanding of focal doctors' behavior in the online health communities by exploring the mediating role of their peers' economic and social returns. The results of this paper extend the research in the field of peer effect and online health and provide management implications and suggestions for online health platforms and doctors.