bluuebunny/crossref_metadata_2025_split huggingface dataset:
A brain-rhythm based computational framework for semantic context and acoustic signal integration in speech processing
Authors: Dogonasheva Olesia , Doelling Keith , Zakharov Denis , Giraud Anne-Lise , Gutkin Boris 
Published: January 2024

AbstractUnraveling the mysteries of how humans effortlessly grasp speech despite diverse environmental challenges has long intrigued researchers in systems and cognitive neuroscience. This study explores the neural intricacies underpinning robust speech comprehension, giving computational mechanistic proof for the hypothesis proposing a pivotal role for rhythmic, predictive top-down contextualization facilitated by the delta rhythm in achieving time-invariant speech processing. Our Brain-Rhythm-based Inference model, BRyBI, integrates three key rhythmic processes – theta-gamma interactions for parsing phoneme sequences, dynamic delta rhythm for inferred prosodic-phrase context, and resilient speech representations. Demonstrating mechanistic proof-of-principle, BRyBI replicates human behavioral experiments, showcasing its ability to handle pitch variations, time-warped speech, interruptions, and silences in non-comprehensible contexts. Intriguingly, the model aligns with human experiments, revealing optimal silence time scales in the theta- and delta-frequency ranges. Comparative analysis with deep neural network language models highlights distinctive performance patterns, emphasizing the unique capabilities of a rhythmic framework. In essence, our study sheds light on the neural underpinnings of speech processing, emphasizing the role of rhythmic brain mechanisms in structured temporal signal processing – an insight that challenges prevailing artificial intelligence paradigms and hints at potential advancements in compact and robust computing architectures.
The Role of Rhizosphere Microorganisms and CNPS Genes in Shaping Nutritional Traits of Capsicum
Authors: Tao Yu , Zhang Mingxing , Peng Siwen , Long Shiping , Zou Xuexiao , Li Xin 
Published: January 2024

AbstractThe rhizosphere microbiota plays crucial roles in biogeochemical cycling and primary production. However, there is a lack of research exploring the complex relationships between microbiota and their functional traits in pepper rhizospheres, as well as their impact on nutrient cycling processes. Here, we investigated the effects of pepper species on the rhizomicrobiota and functional genes (C/N/P/S) on nutrient absorptions and accumulations in pepper organs. The results revealed that Pepper YZ/BE had higher N content in all compartments, which could be attributed to the presence of enriched N-metabolic microbes (Gaiellales/Leifsonia) and higher expression of N availability-promoting genes (ureC/amoA2/nxrA/napA) in rhizospheres. Additionally, we utilized co-occurrence network analysis and partial least squares path modeling (PLS-PM) to understand the interactions among the variables. The bacterial network exhibited more associations than the fungal network, and the abundance of certain modules positively correlated with the expression of CNPS genes, which thus significantly influenced pepper nutrient content. The PLS-PM analysis demonstrated that taxa abundance in network modules, functional genes, and rhizospheric soil properties collectively explained 92% of the variance in pepper nutrient content. Overall, this study provides valuable experimental and theoretical insights into the effects of rhizosphere microorganisms and CNPS genes on the nutritional traits ofCapsicum.HighlightThe rizho-bacterial community harbored more robust relationships than the fungal ones, which formed the functional clusters highly linking to the below- and aboveground nutrient properties of pepper species.
The type of inhibition provided by thalamic interneurons alters the input selectivity of thalamocortical neurons
Authors: Djama Deyl , Zirpel Florian , Ye Zhiwen , Moore Gerald , Chue Charmaine , Edge Christopher , Jager Polona , Delogu Alessio , Brickley Stephen G 
Published: January 2024

AbstractA fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neuron’s selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.
Estrogen-related differences in antitumor immunity and the gut microbiome contribute to sexual dimorphism of colorectal cancer
Authors: Lattanzi Georgia , Perillo Federica , Díaz-Basabe Angélica , Caridi Bruna , Amoroso Chiara , Baeri Alberto , Cirrincione Elisa , Ghidini Michele , Galassi Barbara , Cassinotti Elisa , Baldari Ludovica , Boni Luigi , Vecchi Maurizio , Caprioli Flavio , Facciotti Federica , Strati Francesco 
Published: January 2024

AbstractColorectal cancer (CRC) is a multifaceted disease whose development and progression varies depending on tumor location, age of patients, infiltration of immune cells within cancer lesions, and the tumor microenvironment. These pathophysiological characteristics are additionally influenced by sex-related differences. The gut microbiome plays a pivotal role in the initiation and progression of CRC, and shapes anti-tumor immune responses but how the responsiveness of the immune system to the intestinal microbiota may contribute to the sexual dimorphism of CRC is largely unknown. Here, we studied survival, tumor-infiltrating immune cell populations and tumor-associated microbiome of a cohort of n=184 male and female CRC patients and functionally tested the immune system-microbiome interactions inin vivoandin vitromodels of the disease. High-dimensional single-cell flow cytometry showed that female patients are enriched by tumor-infiltrating iNKT cells but depleted by cytotoxic T lymphocytes. The enrichment of oral pathobionts and a reduction of β-glucuronidase activity are distinctive traits characterizing the gut microbiome of women affected by CRC. Functional assays using a collection of human primary iNKT cell lines demonstrated that the gut microbiota of female patients functionally impairs iNKT cell anti-tumor functions interfering with the granzyme-perforin cytotoxic pathway. These results highlight a sex-dependent functional relationship between the gut microbiome, estrogen metabolism, and the decline of cytotoxic T cell responses, contributing to the sexual dimorphism observed in CRC patients with relevant implications for precision medicine and the design of targeted therapeutic approaches addressing sex bias in cancer.
Novel FKBP12 ligand promotes functional improvement in SOD1G93AALS mice
Authors: Moreno-Martinez Laura , Gaja-Capdevila Núria , Mosqueira-Martín Laura , Herrando-Grabulosa Mireia , Gonzalez-Imaz Klaudia , Calvo Ana C. , Sagartzazu-Aizpurua Maialen , Moreno-García Leticia , Fuentes Jose Manuel , Acevedo-Arozena Abraham , Aizpurua Jesús María , Miranda José Ignacio , de Munain Adolfo López , Vallejo-Illarramendi Ainara , Navarro Xavier , Osta Rosario , Gil-Bea Francisco Javier 
Published: January 2024

SUMMARYAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with limited treatment options. ALS pathogenesis involves intricate processes within motor neurons (MNs), characterized by dysregulated Ca2+influx and buffering in early ALS-affected MNs. This study proposes the modulation of ryanodine receptors (RyRs), key mediators of intracellular Ca2+, as a therapeutic target. A novel class of novel FKBP12 ligands that show activity as cytosolic calcium modulators through stabilizing RyR channel activity, were tested in the SOD1G93Amouse model of ALS. Different outcomes were used to assess treatment efficacy including electrophysiology, histopathology, neuromuscular function, and survival. Among the novel FKBP12 ligands, MP-010 was chosen for its central nervous system availability. Chronic administration of MP-010 to SOD1G93Amice produced a dose-dependent preservation of motor nerve conduction, with the 61 mg/kg dose significantly delaying the onset of motor impairment. This was accompanied by improved motor coordination, increased innervated endplates, and significant preservation of MNs in the spinal cord of treated mice. Notably, MP-010 treatment significantly extended lifespan by an average of 10 days compared to vehicle. In conclusion, FKBP12 ligands, particularly MP-010, exhibit promising neuroprotective effects in ALS, highlighting their potential as novel therapeutic agents. Further investigations into the molecular mechanisms and clinical translatability of these compounds are needed for their application in ALS treatment.
Epigenetic control of multiple genes with a single lentiviral vector encoding transcriptional repressors fused to compact zinc finger arrays
Authors: Monteferrario Davide , David Marion , Tadi Satish K. , Zhou Yuanyue , Marchetti Irène , Jeanneau Caroline , Saviane Gaëlle , Dupont Coralie F. , Martelli Angélique E. , Truong Lynn , Eshleman Jason , Ng Colman , Huston Marshall , Davis Gregory D. , Fontenot Jason D. , Reik Andreas , de la Rosa Maurus , Fenard David 
Published: January 2024

ABSTRACTGene silencing without gene editing holds great potential for the development of safe therapeutic applications. Here, we describe a novel strategy to concomitantly repress multiple genes using zinc finger proteins fused to Krüppel-Associated Box repression domains (ZF-Rs). This was achieved via the optimization of a lentiviral system tailored for the delivery of ZF-Rs in hematopoietic cells. We showed that an optimal design of the lentiviral backbone is crucial to multiplex up to three ZF-Rs or two ZF-Rs and a chimeric antigen receptor. ZF-R expression had no impact on the integrity and functionality of transduced cells. Furthermore, gene repression in ZF-R-expressing T cells was highly efficientin vitroandin vivoduring the entire monitoring period (up to ten weeks), and it was accompanied by epigenetic remodeling events. Finally, we described an approach to improve ZF-R specificity to illustrate the path towards the generation of ZF-Rs with a safe clinical profile. In conclusion, we successfully developed an epigenetic-based cell engineering approach for concomitant modulation of multiple gene expressions that bypass the risks associated with DNA editing.
PatternJ: an ImageJ toolset for the automated and quantitative analysis of regular spatial patterns found in sarcomeres, axons, somites, and more
Authors: Blin Mélina Baheux , Loreau Vincent , Schnorrer Frank , Mangeol Pierre 
Published: January 2024

AbstractRegular spatial patterns are ubiquitous forms of organization in nature. In animals, regular patterns can be found from the cellular scale to the tissue scale, and from early stages of development to adulthood. To understand the formation of these patterns, how they form and mature, and how they are affected by perturbations, a precise quantitative description of the patterns is essential. However, accessible tools that offer in-depth analysis without the need for computational skills are lacking for biologists. Here we present PatternJ, a novel toolset to analyze regular pattern organizations precisely and automatically. This toolset, to be used with the popular imaging processing program ImageJ/Fiji, facilitates the extraction of key geometric features within and between pattern repeats. We validated PatternJ on simulated data and tested it on images of sarcomeres in insect muscles and cardiomyocytes, actin rings in neurons, and somites in zebrafish embryos obtained using confocal fluorescence microscopy, STORM, electron microscopy, and bright-field imaging. We show that the toolset delivers subpixel feature extraction reliably even with images of low signal-to-noise ratio. PatternJ’s straightforward use and functionalities make it valuable for various scientific fields requiring quantitative pattern analysis, including the sarcomere biology of muscles or the patterning of mammalian axons, speeding up discoveries with the bonus of high reproducibility.
Histological analysis of Scots pine (Pinus sylvestrisL.) seedlings in response to root rot pathogenHeterobasidion annosuminoculation
Authors: Youssef Khaled , Marttila Salla 
Published: January 2024

AbstractHeterobasidionroot rot is one of the most serious and economically destructive forest diseases in the Northern Hemisphere. Although several studies have explored the genetic and chemical responses of Scots pine toHeterobasidionspp. infection, the histological defense responses of this species remain poorly understood. In this study, we investigated the histological responses of three-year-old Scots pine seedlings toHeterobasidion annosuminoculation and a wounding treatment with no inoculation, focusing on lesion length and traumatic resin-duct characteristics (density, size). Our results showed thatH. annosum-inoculated seedlings exhibited significantly more browning necrotic lesions than wounded seedlings. Traumatic resin duct density was significantly higher inH. annosum-inoculated seedlings compared to wounded seedlings, particularly within the first two cm from the inoculation point. However, as the distance from the inoculation point increased, the resin duct density decreased. Notably, there were neither statistically significant differences in the mean size of traumatic and constitutive resin ducts between the two treatments, nor within theH. annosuminoculation treatment itself. In contrast, within the wound treatment, the mean size of traumatic resin ducts was found to be significantly smaller than that of constitutive resin ducts. Furthermore, traumatic resin ducts did not prove to be reliable markers for datingH. annosuminfection in Scots pine. Overall, this study advances knowledge about Scots pine’s histological defense mechanisms againstH. annosuminvasion, which has significant implications.
A fast and sensitive size-exclusion chromatography method for plasma extracellular vesicle proteomic analysis
Authors: Ludovico Ivo Díaz , Powell Samantha M. , Many Gina , Bramer Lisa , Sarkar Soumyadeep , Stratton Kelly , Liu Tao , Shi Tujin , Qian Wei-Jun , Burnum-Johnson Kristin E , Melchior John T. , Nakayasu Ernesto S. 
Published: January 2024

AbstractExtracellular vesicles (EVs) carry diverse biomolecules derived from their parental cells, making their components excellent biomarker candidates. However, purifying EVs is a major hurdle in biomarker discovery since current methods require large amounts of samples, are time-consuming and typically have poor reproducibility. Here we describe a simple, fast, and sensitive EV fractionation method using size exclusion chromatography (SEC) on a fast protein liquid chromatography (FPLC) system. Our method uses a Superose 6 Increase 5/150, which has a bed volume of 2.9 mL. The FPLC system and small column size enable reproducible separation of only 50 µL of human plasma in 15 minutes. To demonstrate the utility of our method, we used longitudinal samples from a group of individuals that underwent intense exercise. A total of 838 proteins were identified, of which, 261 were previously characterized as EV proteins, including classical markers, such as cluster of differentiation (CD)9 and CD81. Quantitative analysis showed low technical variability with correlation coefficients greater than 0.9 between replicates. The analysis captured differences in relevant EV-proteins involved in response to physical activity. Our method enables fast and sensitive fractionation of plasma EVs with low variability, which will facilitate biomarker studies in large clinical cohorts.
The N-terminus ofPlasmodium falciparumCircumsporozoite Protein Contains Three Non-Overlapping Murine B-cell Epitope Regions
Authors: Beutler Nathan , Garcia Elijah , Lai Yen-Chung , Ndihokubwayo Justin , Gambuzza Kiara , Zhao Jerry , Burton Dennis R. , Rogers Thomas F. 
Published: January 2024

AbstractThe generation of an anti-malarial vaccine that produces broad, potent, and durable responses is highly desirable to control the burden ofPlasmodium falciparumdisease. Current vaccines have offered modest efficacy ranging from 50%-70%, likely associated with antibody responses that are relatively short lived and strain specific. Currently approved malaria vaccines, RTS,S and R21, target the repeat region and C-terminal region ofPlasmodium falciparumCSP, leaving the N-terminal region of CSP neglected as a target for protective immunogen design. Here, we isolate and express a panel of memory B-cell derived N-terminal CSP-specific monoclonal antibodies (mAbs) from mice immunized with an N-terminal CSP specific immunogen. The characterization of N-terminal specific mAbs including peptide walking and affinity experiments indicate that these antibodies target three distinct sites within the N-terminus of CSP. Site ntCSP-A contains the Region I (RI) cleavage site, which has been previously defined, whereas the remaining two sites are in previously undescribed locations upstream of RI, termed ntCSP-B and ntCSP-C.
nf-core/airrflow: an adaptive immune receptor repertoire analysis workflow employing the Immcantation framework
Authors: Gabernet Gisela , Marquez Susanna , Bjornson Robert , Peltzer Alexander , Meng Hailong , Aron Edel , Lee Noah Y. , Jensen Cole , Ladd David , Hanssen Friederike , Heumos Simon ,   nf-core community, Yaari Gur , Kowarik Markus C. , Nahnsen Sven , Kleinstein Steven H. 
Published: January 2024

ABSTRACTAdaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a valuable experimental tool to study the immune state in health and following immune challenges such as infectious diseases, (auto)immune diseases, and cancer. Several tools have been developed to reconstruct B cell and T cell receptor sequences from AIRR-seq data and infer B and T cell clonal relationships. However, currently available tools offer limited parallelization across samples, scalability or portability to high-performance computing infrastructures. To address this need, we developed nf-core/airrflow, an end-to-end bulk and single-cell AIRR-seq processing workflow which integrates the Immcantation Framework following BCR and TCR sequencing data analysis best practices. The Immcantation Framework is a comprehensive toolset, which allows the processing of bulk and single-cell AIRR-seq data from raw read processing to clonal inference. nf-core/airrflow is written in Nextflow and is part of the nf-core project, which collects community contributed and curated Nextflow workflows for a wide variety of analysis tasks. We assessed the performance of nf-core/airrflow on simulated sequencing data with sequencing errors and show example results with real datasets. To demonstrate the applicability of nf-core/airrflow to the high-throughput processing of large AIRR-seq datasets, we validated and extended previously reported findings of convergent antibody responses to SARS-CoV-2 by analyzing 97 COVID-19 infected individuals and 99 healthy controls, including a mixture of bulk and single-cell sequencing datasets. Using this dataset, we extended the convergence findings to 20 additional subjects, highlighting the applicability of nf-core/airrflow to validate findings in small in-house cohorts with reanalysis of large publicly available AIRR datasets.Availability and implementationnf-core/airrflow is available free of charge, under the MIT license on GitHub (https://github.com/nf-core/airrflow). Detailed documentation and example results are available on the nf-core website at (https://nf-co.re/airrflow).Visual abstract
Acceleration of HDL-mediated cellular cholesterol efflux alleviates periodontitis
Authors: Tran Thanh-Tam , Lee Gyuseok , Huh Yun Hyun , Chung Ki-Ho , Lee Sun Young , Park Ka Hyon , Kook Min-Suk , Ryu Jaeyoung , Kim Ok-Su , Lim Hyun-Pil , Koh Jeong-Tae , Ryu Je-Hwang 
Published: January 2024

ABSTRACTPeriodontitis (PD) is a common inflammatory disease known to be closely associated with metabolic disorders, particularly hyperlipidemia. However, direct evidence is lacking, and the molecular mechanism is yet to be examined. In the current study, we demonstrated that hypercholesterolemia is a causative factor in the development of PD. Logistic regression analysis revealed a strong positive correlation between PD and dyslipidemia. Data fromin vivo(PD mouse model subjected to a high cholesterol diet) andin vitro(cholesterol treatment of periodontal cells) experiments showed that excess cholesterol influx into periodontal cells potentially contributes to periodontal inflammation and subsequently, alveolar bone erosion. Additionally, we compared the protective efficacies of cholesterol-lowering drugs with their different modes of action against PD pathogenesis in mice. Among the cholesterol-lowering drugs we tested, fenofibrate exerted the most protective effect against PD pathogenesis, due to an increased level of high-density lipoprotein cholesterol, a lipoprotein involved in cholesterol efflux from cells and reverse cholesterol transport. Indeed, cholesterol efflux was suppressed during PD progression by downregulation of the apoA-I binding protein (APOA1BP) expression in inflamed gingival fibroblasts and periodontal ligament cells. We also demonstrated that the overexpression of APOA1BP efficiently regulated periodontal inflammation and the subsequent alveolar bone loss by inducing cholesterol efflux. Our collective findings highlight the potential utility of currently available cholesterol-lowering medications for the mitigation of PD pathogenesis. By targeting the acceleration of high-density lipoprotein (HDL)-mediated cellular cholesterol efflux, a new therapeutic approach for PD may become possible.
Regulatory and evolutionary impact of DNA methylation in two songbird species and their naturally occurring F1hybrids
Authors: Boman Jesper , Qvarnström Anna , Mugal Carina F. 
Published: January 2024

AbstractRegulation of transcription by DNA methylation in 5’-CpG-3’ context is a widespread mechanism allowing differential expression of genetically identical cells to persist throughout development. Consequently, differences in DNA methylation can reinforce variation in gene expression among cells, tissues, populations and species. Despite a surge in studies on DNA methylation, we know little about the importance of DNA methylation in population differentiation and speciation. Here we investigate the regulatory and evolutionary impact of DNA methylation in five tissues of twoFicedulaflycatcher species and their naturally occurring F1hybrids. We show that the density of CpG in the promoters of genes determines the strength of the association between gene expression and DNA methylation. The impact of DNA methylation on gene expression varies among tissues with brain showing unique patterns. Differentially expressed genes between parental species are predicted by genetic– and methylation differentiation in CpG-rich promoters. However, both these factors fail to predict hybrid misexpression suggesting that promoter mismethylation is not a main determinant of hybrid misexpression inFicedulaflycatchers. Using allele-specific methylation estimates in hybrids we also determine the genome-wide contribution ofcis-andtranseffects in DNA methylation differentiation. These distinct mechanisms are roughly balanced in all tissues except brain, wheretransdifferences predominate. Overall, this study provides insight on the regulatory and evolutionary impact of DNA methylation in songbirds.