bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flexible hippocampal representation of abstract boundaries supports memory-guided choice
Authors: Esposito Mariachiara , Abdul Lubna , Ghouse Ameer , Rodriguez Aramendía Marta , Kaplan Raphael 
Published: July 2024

AbstractHippocampal cognitive maps encode the relative locations of spatial cues in an environment and adapt their representation when boundaries geometrically change. Hippocampal cognitive maps can represent abstract knowledge, yet it’s unclear whether the hippocampus is sensitive to changes to the extreme coordinates, boundaries, of abstract spaces. We created a memory-guided choice task to test whether the human hippocampus and medial prefrontal cortex(mPFC) flexibly learn abstract boundary representations in distinct two-dimensional(2D) knowledge spaces. Participants built up a 2D map-like representation of abstract boundaries, where the hippocampus and mPFC represented a decision cue’s Euclidean distance to the closest boundary. Notably, mPFC distance representations selectively reflected individual performance improvements during the task. Testing for neural sensitivity to boundary-defined contextual changes, only the hippocampus flexibly represented abstract boundaries, which related to choice behavior. These findings suggest that abstract knowledge retrieval within dynamically changing contexts is facilitated by generalized mPFC and flexible hippocampal boundary representations.
Paralemmin-1 controls the nanoarchitecture of the neuronal submembrane cytoskeleton
Authors: Macarrón-Palacios Victor , Hubrich Jasmine , do Rego Barros Fernandes Lima Maria Augusta , Metzendorf Nicole G. , Kneilmann Simon , Trapp Marleen , Acuna Claudio , Patrizi Annarita , D’Este Elisa , Kilimann Manfred W. 
Published: July 2024

SummaryThe Membrane-associated Periodic Skeleton (MPS) is a specialized submembrane cytoskeleton of neuronal cells, characterized by a highly ordered 190 nm periodic lattice, with emerging functions in mechanical resilience, inter- and intracellular signaling, and action potential transmission. Here, we identify Paralemmin-1 (Palm1) as a new component and regulator of the MPS. Palm1 binds to the N-terminal region of βII-spectrin, a core MPS component, and is periodically organized along the axon in hippocampal neurons. Applying the 3D imaging power of MINFLUX, we locate Palm1 in close proximity (<20 nm) to the actin-capping protein and MPS component adducin. Functionally, Palm1 overexpression enhances the degree of periodicity of several MPS proteins (βII-spectrin, adducin, and ankyrinB) without altering their local concentrations, while the knock-out severely compromises the MPS structure and modifies electrophysiological properties of neurons. Both the MPS-binding and remodelling activities of Palm1 are abolished by mutating a single amino acid (W54A) in the conserved Paralemmin sequence motif. Our findings identify Palm1 as the first protein specifically dedicated to organizing the MPS, and will advance the understanding of the regulation of MPS assembly and remodelling, as well as of the Paralemmin protein family.
Contrasting topologies of synchronous and asynchronous functional brain networks
Authors: McIntyre Clayton C. , Bahrami Mohsen , Shappell Heather M. , Lyday Robert G. , Fish Jeremie , Bollt Erik M. , Laurienti Paul J. 
Published: July 2024

AbstractWe generated asynchronous functional networks (aFNs) using a novel method called optimal causation entropy (oCSE) and compared aFN topology to the correlation-based synchronous functional networks (sFNs) which are commonly used in network neuroscience studies. Functional magnetic resonance imaging (fMRI) time series from 212 participants of the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study were used to generate aFNs and sFNs. As a demonstration of how aFNs and sFNs can be used in tandem, we used multivariate mixed effects models to determine whether age interacted with node efficiency to influence connection probabilities in the two networks.After adjusting for differences in network density, aFNs had higher global efficiency but lower local efficiency than the sFNs. In the aFNs, nodes with the highest outgoing global efficiency tended to be in the brainstem and orbitofrontal cortex. aFN nodes with the highest incoming global efficiency tended to be members of the Default Mode Network (DMN) in sFNs. Age interacted with node global efficiency in aFNs and node local efficiency in sFNs to influence connection probability. We conclude that the sFN and aFN both offer information about functional brain connectivity which the other type of network does not.
PA28γ promotes the malignant progression of tumor by elevating mitochondrial function via C1QBP
Authors: Wang Jiongke , Shi Yujie , Wang Ying , Shen Yingqiang , Liu Huan , Sun Silu , Wang Yimei , Zhou Xikun , Zhou Yu , Zeng Xin , Li Jing , Chen Qianming 
Published: July 2024

AbstractProteasome activator 28γ (PA28γ) plays a critical role in malignant progression of various tumors, however, its role and regulation are not well understood. Here, using oral squamous cell carcinoma (OSCC) as main research model, we discovered that PA28γ interacted with complement 1q binding protein (C1QBP), which is dependent on the N-terminus of C1QBP rather than the known functional domain (amino acids 168-213). Notably, we found that PA28γ enhances C1QBP protein stability in OSCC. Functionally, PA28γ contributes to the malignant progression of OSCC by affecting mitochondrial morphology and oxidative phosphorylation (OXPHOS) through C1QBP in vitro and vivo. Mechanically, PA28γ upregulates the expression of optic atrophy 1 (OPA1), mitofusin 1 (MFN1), mitofusin 2 (MFN2), and the mitochondrial respiratory complex via C1QBP. Moreover, in a clinical cohort of OSCC patients, PA28γ was positively correlated with C1QBP expression and negatively correlated with prognosis. Therefore, C1QBP represents a potential therapeutic target for cancer treatment and prognosis.
FISH, a new tool for in situ preservation of RNA in tissues of deep-sea mobile fauna
Authors: Cueff-Gauchard V. , Aube J. , Lagadec J-R. , Bignon L. , Lafontaine J-P. , Hernandez-Avila I. , Marsaud N. , Shillito B. , Amand L. , Roussel E. G. , Cambon M-A. 
Published: July 2024

ABSTRACTAccessing the metabolic functioning of deep-sea animals in situ remains a technological challenge as the recovery time of samples is incompatible with the short lifespan of such molecules as mRNAs. Tools able to preserve RNA in situ exist but they are incompatible with the study of mobile fauna. Here we describe a new sampling tool, named FISH (Fixer In situ of Homogenized Substrates), implemented on a submersible and equipped with a number of new specific features to collect and preserve in situ tissue of mobile fauna. Connected to the suction pump of a submersible, FISH incorporates a sampling bowl to which two bottles of a preservative reagent are attached, a suction hose, and a support containing a motor connected to the sampling bowl by a magnetic coupling system. We used the deep-sea hydrothermal shrimpRimicaris exoculatafrom the Mid-Atlantic Ridge as a model to test the suitability of our new tool. FISH was compared to two other sampling methods, which use a metatranscriptomic approach targeting microbial communities associated with cephalothorax symbionts. RNA quality, gene assignment and taxonomic and gene function diversity showed differences between in situ and on-board preservation of tissues. Of the alternative sampling methods tested, the suction sampler was clearly not suitable for RNA-based studies, while pressurized recovery showed results closer to the sample quality obtained with FISH sampling. The FISH sampler has therefore demonstrated to be a cost-effective and reliable tool to efficiently preserve RNA recovered from deep-sea environments.
ThePlasmodiophora brassicaeeffector PbEGF1 manipulates plant immunity and regulate primary infection
Authors: Yang Hui , Xu Yushu , Zhao Yushan , Shu Yinping , Sun Xin , Du Junbo 
Published: July 2024

AbstractPlasmodiophora brassicaecauses a significant global threat to cruciferous vegetables and crops. However, the current comprehensions of its pathogenic ways is still unclear. This study identified aP. brassicaeeffector, called PbEGF1, which strongly induces cell death inN. benthamiana.Notably,PbEGF1was significantly up-regulated in seedlings inoculated with highly virulentP. brassicae, indicating a pivotal role for PbEGF1 in pathogenicity. Furthermore, overexpression of PbEGF1 in hosts enhanced susceptibility toP. brassicae,and promoted elongation of root hairs, thus creating favorable conditions for root hair infection. Silencing ofPbEGF1reduced the pathogenicity ofP. brassicae. This finding confirms the significance of primary infection in host recognition and interaction withP. brassicae. To further elucidate the virulence function of PbEGF1, we identified BnNHL13 (nonrace-specific disease resistance 1/harpin-induced 1-like 13) as its target protein. SilencingBnNHL13enhanced host susceptibility toP. brassicae,and promoted root hairs elongation, indicating that down-regulation ofBnNHL13was more conducive to establishingP. brassicaeinfection. Subsequent investigation revealed that PbEGF1 has the ability to induce degradation of the BnNHL13 protein, thereby disrupting the host defense response and facilitatingP. brassicaeinfection. Our findings provide novel insights into genetic strategies for enhancing plant resistance against clubroot disease.
Protein Kinases MpkA and SepH Transduce Crosstalk Between CWI and SIN Pathways to Activate Protective Hyphal Septation Under Echinocandin Cell Wall Stress
Authors: Doan Alexander G. , Schafer Jessica E. , Douglas Casey M. , Quintanilla Matthew S. , Morse Meredith E. , Edwards Harley , Huso Walker D. , Gray Kelsey J. , Lee JungHun , Dayie Joshua K. , Harris Steven D. , Marten Mark R. 
Published: July 2024

ABSTRACTThis study investigates a previously unreported stress signal transduced as crosstalk between the Cell Wall Integrity (CWI) pathway and the Septation Initiation Network (SIN). Echinocandins, which target cell wall synthesis, are widely used to treat mycoses. Their efficacy, however, is species specific; our findings suggest this is due largely to CWI-SIN crosstalk and the ability of filamentous species to fortify with septa in response to echinocandin stress. To better understand this crosstalk, we used a microscopy-based assay to measure septum density, aiming to understand the septation response to cell wall stress. The echinocandin micafungin, an inhibitor of β-(1,3)-glucan synthase, was employed to induce this stress. We observed a strong positive correlation between micafungin treatment and septum density inwild-typestrains. This finding suggests that CWI activates SIN under cell wall stress, increasing septum density to protect against cell wall failure. More detailed investigations, with targeted knockouts of CWI and SIN signaling proteins, enabled us to identify crosstalk occurring between the CWI kinase, MpkA, and the SIN kinase, SepH. This discovery, of previously unknown crosstalk between the CWI and SIN pathways, not only reshapes our understanding of fungal stress responses, but also unveils a promising new target pathway for the development of novel antifungal strategies.IMPORTANCEEchinocandin resistant species pose a major challenge in clinical mycology by rendering one of only four lines of treatment, notably one of the two that are well-tolerated, ineffective in treating systemic mycoses of these species. Previous studies have demonstrated that echinocandins fail against highly polarized fungi because they target only apical septal compartments. It is known that many filamentous species respond to cell wall stress with hyperseptation. In this work we show that echinocandin resistance hinges on this dynamic response, rather than on innate septation alone. We also unveil, for the first time, the signaling pathway used to deploy the hyperseptation response. By disabling this pathway, we were able to render mycelia susceptible to echinocandin stress. Hence, this work enhances our microbiological understanding of filamentous fungi and introduces a potential target to overcome echinocandin resistant species.
Chemical Induction of Longevity-Promoting Colanic Acid in the Host’s Microbiota
Authors: Hu Guo , Cooke Matthew Brandon , Wen Alice X , Yu Xin , Wang Jin , Herman Christophe , Wang Meng C. 
Published: July 2024

AbstractMicrobiota-derived metabolites have emerged as key regulators of longevity. The metabolic activity of the gut microbiota, influenced by dietary components and ingested chemical compounds, profoundly impacts host fitness. While the benefits of dietary prebiotics are well-known, chemically targeting the gut microbiota to enhance host fitness remains largely unexplored. Here, we report a novel chemical approach to induce a pro-longevity bacterial metabolite in the host gut. We discovered that specificEscherichia colistrains overproduce colanic acids (CAs) when exposed to a low dose of cephaloridine, leading to an increased lifespan in hostCaenorhabditis elegans. In the mouse gut, oral administration of low-dose cephaloridine induces the transcription of the capsular biosynthesis operon responsible for CA biosynthesis in commensalE. coli, which overcomes the inhibition of CA biosynthesis above 30°C and enables its induction directly from the microbiota. Importantly, low-dose cephaloridine induces CA independently of its antibiotic properties through a previously unknown mechanism mediated by the membrane-bound histidine kinase ZraS. Our work lays the foundation for microbiota-based therapeutics through the chemical modulation of bacterial metabolism and reveals the promising potential of bacteria-targeting drugs in promoting host longevity.
The single-cell make-up of adult diffuse glioma based on the 2021 WHO classification
Authors: Alnahhas Iyad , Kayne Allison , Khan Mehak , Shi Wenyin 
Published: July 2024

AbstractIntroductionSingle-cell RNA sequencing (scRNA-seq) has helped to elucidate the cellular composition of cancer and its microenvironment. Recent scRNA-seq studies have highlighted the heterogeneity of glioblastoma (GBM). Moreover, single-cell GBM analyses have proposed resemblance of GBM cells to radial glia and outer radial glia supporting the hypothesis that remnants of developmental tissue get reactivated in cancer. A recent study isolated neural progenitor cells (NPCs) from developing fetal human brain (gestational week 17–19) and classified NPCs based on their expression of THY1, CD24 and EGFR. Ventricular radial glia are THY1-CD24-EGFR+ whereas outer radial glia are THY1-CD24-EGFR-. Early neuron precursors are CD24+THY1-EGFR+ and glial progenitor cells (GPCs) are THY1+EGFR+. GPCs give rise to THY1+EGFR+PDGFRA+ pre-oligodendrocyte progenitor cells. The importance of EGFR in NPCs again highlights the resemblance to glioma.MethodsWe aimed to apply the classification above in IDH mutant astrocytoma and oligodendroglioma as well as IDHwt glioblastoma samples. We used three publicly available datasets: Wang (paired 74 IDHwt primary and recurrent samples), Tirosh (6 primary oligodendroglioma samples) and Venteicher (10 primary IDH mutant astrocytoma).ResultsIn IDH mutant astrocytoma, 82.63% of cells express THY1+ (mostly EGFR+PDGFRA+) and 10.76% of cells are THY1-CD24-EGFR+. In oligodendroglioma, 75% of cells are THY1+ (mostly EGFR+PDGFRA+) and 12.07% are THY1-CD24-EGFR+. In IDHwt EGFR amplified primary GBM samples, 87.5% of cells are THY1-CD24-EGFR+. This percentage drops to 70.4% in the recurrent setting. THY1-CD24-EGFR-cells increase from 9.7% to 23.1% at recurrence. In IDHwt EGFRwt primary GBM samples, 48.6% of cells are THY1-CD24-EGFR+ and 44.15% are THY1-CD24-EGFR-. In the recurrent setting, 43.26% of cells are THY1-CD24-EGFR+ and 49.58% are THY1-CD24-EGFR-.ConclusionIDH mutant gliomas and IDHwt glioblastoma express different progenitor cell markers. THY1 is highly expressed in IDH mutant gliomas.
Eco-evolutionary dynamics of pathogen immune-escape: deriving a population-level phylodynamic curve
Authors: Nielsen Bjarke Frost , Saad-Roy Chadi M. , Metcalf C. Jessica E. , Viboud Cécile , Grenfell Bryan T. 
Published: July 2024

AbstractThe phylodynamic curve [1] conceptualizes how immunity shapes the rate of viral adaptation in a non-monotonic fashion, through its opposing effects on viral abundance and the strength of selection. However, concrete and quantitative model realizations of this influential concept are rare. Here, we present an analytic, stochastic framework in which a population-scale phylodynamic curve emerges dynamically, allowing us to address questions regarding the risk and timing of emergence of viral immune escape variants. We explore how pathogen- and population-specific parameters such as strength of immunity, transmissibility and antigenic constraints affect the phylodynamic curve, leading to distinct phylodynamic curves for different pathogens. Motivated by the COVID-19 pandemic, we probe the likely effects of non-pharmaceutical interventions (NPIs), and the lifting thereof, on the risk of viral escape variant emergence. Looking ahead, the framework has the potential to become a useful tool for probing how natural immunity, as well as choices in vaccine design and distribution and the implementation of NPIs affect the evolution of common viral pathogens.
Activating FcγRs on monocytes are necessary for optimal Mayaro virus clearance
Authors: Dunagan Megan M. , Dábilla Nathânia , McNinch Colton , Brenchley Jason M. , Dolan Patrick T. , Fox Julie M. 
Published: July 2024

AbstractMayaro virus (MAYV) is an emerging arbovirus. Previous studies have shown antibody Fc effector functions are critical for optimal monoclonal antibody-mediated protection against alphaviruses; however, the requirement of Fc gamma receptors (FcγRs) for protection during natural infection has not been evaluated. Here, we showed mice lacking activating FcγRs (FcRγ-/-) developed prolonged clinical disease with more virus in joint-associated tissues. Viral clearance was associated with anti-MAYV cell surface binding rather than neutralizing antibodies. Lack of Fc-FcγR engagement increased the number of monocytes through chronic timepoints. Single cell RNA sequencing showed elevated levels of pro-inflammatory monocytes in joint-associated tissue with increased MAYV RNA present in FcRγ-/-monocytes and macrophages. Transfer of FcRγ-/-monocytes into wild type animals was sufficient to increase virus in joint-associated tissue. Overall, this study suggests that engagement of antibody Fc with activating FcγRs promotes protective responses during MAYV infection and prevents monocytes from being potential targets of infection.
Distinct subcircuits within the mesolimbic dopamine system encode the salience and valence of social stimuli
Authors: Cross E. A. , Borland J.M. , Shaughnessy E.K. , Lee S.D. , Vu V. , Sambor E.A. , Huhman K. L. , Albers H. E. 
Published: July 2024

AbstractThe mesolimbic dopamine (DA) system (MDS) is the canonical “reward” pathway that has been studied extensively in the context of the rewarding properties of sex, food, and drugs of abuse. In contrast, very little is known about the role of the MDS in the processing of the rewarding and aversive properties of social stimuli. Social interactions can be characterized by their salience (i.e., importance) and their rewarding or aversive properties (i.e., valence). Here, we test the novel hypothesis that projections from the medial ventral tegmental area (VTA) to the nucleus accumbens (NAc)corecodes for the salience of social stimuli through the phasic release of DA in response to both rewarding and aversive social stimuli. In contrast, we hypothesize that projections from the lateral VTA to the NAcshellcodes for the rewarding properties of social stimuli by increasing the tonic release of DA and the aversive properties of social stimuli by reducing the tonic release of DA. Using DA amperometry, which monitors DA signaling with a high degree of temporal and anatomical resolution, we measured DA signaling in the NAc core or shell while rewarding and aversive social interactions were taking place. These findings, as well as additional anatomical and functional studies, provide strong support for the proposed neural circuitry underlying the response of the MDS to social stimuli. Together, these data provide a novel conceptualization of how the functional and anatomical heterogeneity within the MDS detect and distinguish between social salience, social reward, and social aversion.Significance StatementSocial interactions of both positive and negative valence are highly salient stimuli that profoundly impact social behavior and social relationships. Although DA projections from the VTA to the NAc are involved in reward and aversion little is known about their role in the saliency and valence of social stimuli. Here, we report that DA projections from the mVTA to the NAc core signal the salience of social stimuli, whereas projections from the lVTA to the NAc shell signal valence of social stimuli. This work extends our current understanding of the role of DA in the MDS by characterizing its subcircuit connectivity and associated function in the processing of rewarding and aversive social stimuli.
Cell Storage Conditions Impact Single-Cell Proteomic Landscapes
Authors: Onat Bora , Momenzadeh Amanda , Haghani Ali , Jiang Yuming , Song Yang , Parker Sarah J. , Meyer Jesse G. 
Published: July 2024

AbstractSingle-cell transcriptomics (SCT) has revolutionized our understanding of cellular heterogeneity, yet the emergence of single-cell proteomics (SCP) promises a more functional view of cellular dynamics. A challenge is that not all mass spectrometry facilities can perform SCP, and not all labs have access to cell sorting equipment required for SCP, which together motivate an interest in sending bulk cell samples through the mail for sorting and SCP analysis. Shipping requires cell storage, which has an unknown impact on SCP results. This study investigates the impact of cell storage conditions on the proteomic landscape at the single-cell level utilizing a Data-Independent Acquisition (DIA) coupled with Parallel Accumulation Serial Fragmentation (diaPASEF). Three storage conditions were compared in 293T cells: (1) 37°C (control), (2) 4°C overnight, and (3) - 80°C storage followed by liquid nitrogen preservation. Either cold or frozen storage induced significant alterations in cell diameter, elongation, and proteome composition. By elucidating how cell storage conditions alter cellular morphology and proteome profiles, this study contributes foundational technical information about SCP sample preparation and data quality.