bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synaptic correlates of the corticocortical circuit in motor learning
Authors: Kim Yeonjun , Hong Ilgang , Kaang Bong-Kiun 
Published: June 2024

Rodents actively learn new motor skills for survival in reaction to changing environments. Despite the classic view of the primary motor cortex (M1) as a simple muscle relay region, it is now known to play a significant role in motor skill acquisition. The secondary motor cortex (M2) is reported to be a crucial region for motor learning as well as for its role in motor execution and planning. Although these two regions are known for the part they play in motor learning, the role of direct connection and synaptic correlates between these two regions remains elusive. Here, we confirm M2 to M1 connectivity with a series of tracing experiments. We also show that the accelerating rotarod task successfully induces motor skill acquisition in mice. For mice that underwent rotarod training, learner mice showed increased synaptic density and spine head size for synapses between activated cell populations of M2 and M1. Non-learner mice did not show these synaptic changes. Collectively, these data suggest the potential importance of synaptic plasticity between activated cell populations as a potential mechanism of motor learning.
This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Rapidly reversible persistent long-term potentiation inhibition by patient-derived brain tau and amyloid ß proteins
Authors: Ondrejcak Tomas , Klyubin Igor , Hu Neng-Wei , Yang Yin , Zhang Qiancheng , Rodriguez Brian J. , Rowan Michael J. 
Published: June 2024

How the two pathognomonic proteins of Alzheimer’s disease (AD); amyloid ß (Aß) and tau, cause synaptic failure remains enigmatic. Certain synthetic and recombinant forms of these proteins are known to act concurrently to acutely inhibit long-term potentiation (LTP). Here, we examined the effect of early amyloidosis on the acute disruptive action of synaptotoxic tau prepared from recombinant protein and tau in patient-derived aqueous brain extracts. We also explored the persistence of the inhibition of LTP by different synaptotoxic tau preparations. A single intracerebral injection of aggregates of recombinant human tau that had been prepared by either sonication of fibrils (SτAs) or disulfide bond formation (oTau) rapidly and persistently inhibited LTP in rat hippocampus. The threshold for the acute inhibitory effect of oTau was lowered in amyloid precursor protein (APP)-transgenic rats. A single injection of synaptotoxic tau-containing AD or Pick’s disease brain extracts also inhibited LTP, for over two weeks. Remarkably, the persistent disruption of synaptic plasticity by patient-derived brain tau was rapidly reversed by a single intracerebral injection of different anti-tau monoclonal antibodies, including one directed to a specific human tau amino acid sequence. We conclude that patient-derived LTP-disrupting tau species persist in the brain for weeks, maintaining their neuroactivity often in concert with Aß.
This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Abundant Parent-of-origin Effect eQTL in Humans: The Framingham Heart Study
Authors: Guan Yongtao , Levy Daniel 
Published: June 2024

AbstractParent-of-origin effect (POE) is a phenomenon whereby an allele’s effect on a phenotype depends both on its allelic identity and parent from whom the allele is inherited, as exemplified by the polar overdominance in the ovine callypyge locus and the human obesityDLK1locus. Systematic studies of POE of expression quantitative trait loci (eQTL) are lacking. In this study we use trios among participants in the Framingham Heart Study to examine to what extend POE exists for gene expression of whole blood using whole genome sequencing and RNA sequencing. For each gene and the SNPs in cis, we performed eQTL analysis using genotype, paternal, maternal, and joint models, where the genotype model enforces the identical effect sizes on paternal and maternal alleles, and the joint model allows them to have different effect sizes. We compared models using Bayes factors to identify paternal, maternal, and opposing eQTL, where paternal and maternal effects have opposite directions. The resultant variants are collectively called POE eQTL. The highlights of our study include: 1) There are more than 2, 000 genes harbor POE eQTL and majority POE eQTL are not in the vicinity of known imprinted genes; 2) Among 180 genes harboring opposing eQTL, 99 harbor exclusively opposing eQTL, and 58 of the 99 are phosphoprotein coding genes, reflecting significant enrichment; 3) Paternal eQTL are enriched with GWAS hits, and genes harboring paternal eQTL are enriched with drug targets. Our study demonstrates the abundance of POE in gene expression, illustrates the complexity of gene expression regulation, and provides a resource that is complementary to existing resources such as GTEx. We revisited two previous POE findings in light of our POE results. A SNP residing inKCNQ1that is maternally associated with diabetes is a maternal eQTL ofCDKN1C, notKCNQ1. A SNP residing inDLK1that showed paternal polar overdominance for human obesity is a maternal eQTL ofMEG3, offering an explanation for the baseline risk of homozygous samples through association betweenMEG3expression and obesity. Finally, we advised caution on conducting Mendelian randomization using gene expression as the exposure.
Bridging the Gap: biofilm-mediated establishment ofBacillus velezensisonTrichoderma guizhouensemycelia
Authors: Xie Jiyu , Sun Xinli , Xia Yanwei , Tao Lili , Tan Taimeng , Zhang Nan , Xun Weibing , Zhang Ruifu , Kovács Ákos T. , Xu Zhihui , Shen Qirong 
Published: June 2024

AbstractBacterial-fungal interactions (BFIs) are important in ecosystem dynamics, especially within the soil rhizosphere. The bacteriumBacillus velezensisSQR9 and the fungusTrichoderma guizhouenseNJAU 4742 have garnered considerable attention due to their roles in promoting plant growth and protecting their host against pathogens. In this study, we utilized these two model microorganisms to investigate BFI. We firstly demonstrate that while co-inoculation ofB. velezensisandT. guizhouensecould promote tomato growth, these two microorganisms display mutual antagonism on agar solidified medium. To resolve this contradiction, we developed an inoculation method, that allowsB. velezensiscolonization ofT. guizhouensehyphae and performed a transcriptome analysis. During colonization of the fungal hyphae,B. velezensisSQR9 upregulates expression of biofilm related genes (e.g.eps, tasA, andbslA)that is distinct from free-living cells. This result suggested an intricate association between extracellular matrix expression and hyphae colonization. In accordance, deletionepsD, tasA, orbothepsDandtasAgenes ofB. velezensisdiminished colonization of theT. guizhouensehyphae. The insights from our study demonstrate that soil BFIs are more complex than we understood, potentially involving both competition and cooperation. These intricate biofilm-mediated BFI dynamics might contribute to the remarkable diversity observed within soil microbiota, providing a fresh perspective for further exploration of BFIs in the plant rhizosphere.
Multi-strain carriage and intrahost diversity ofStaphylococcus aureusamong Indigenous adults in the US
Authors: Webb Julia , Cella Eleonora , Sutcliffe Catherine , Johnston Catherine , Hassouneh Sayf Al-Deen , Jubair Mohammad , Riley Dennie Parker , Tso Carol , Weatherholtz Robert C. , Hammitt Laura L. , Azarian Taj 
Published: June 2024

ABSTRACTStaphylococcus aureus(SA) is an opportunistic pathogen and human commensal that is frequently present in the upper respiratory tract, gastrointestinal tract, and on the skin. While SA can cause disease ranging from minor skin infections to life-threatening bacteremia, it can also be carried asymptomatically. Indigenous individuals in the Southwest United States experience high rates of invasive SA disease. As carriage is the most significant risk factor for disease, understanding the dynamics of SA carriage, and in particular co-carriage of multiple strains, is important to develop strategies to prevent transmission in vulnerable communities. Here we investigated SA co-carriage and intrahost evolution by performing high density sampling from multiple anatomical sites and whole-genome sequencing (WGS) on 310 SA isolates collected from 60 Indigenous adults participating in a cross-sectional carriage study. We assessed the richness and diversity of SA isolates via differences in multi-locus sequence type (MLST), core-genome single-nucleotide-polymorphisms (SNPs), and genome content. Using WGS data, we identified 95 distinct SA populations among 60 participants; co-carriage was detected in 42% (25/60). Notably, two participants each carried four distinct SA strains. Variation in antibiotic resistance determinants among carried strains was identified among 42% (25/60) of participants. Lastly, we found unequal distribution of clonal complex by body site, suggesting that certain lineages may be adapted to specific anatomical sites. Together, these findings suggest that co-carriage may occur more frequently than previously appreciated and further our understanding of SA intrahost diversity during carriage, which has implications for surveillance activities and epidemiological investigations.
Evaluating the Diagnostic Accuracy of Anti- Zinc Transporter 8 Antibodies in Type 1 Diabetes: A Systematic Review and Meta-Analysis
Authors: de Oliveira Andrade Luís Jesuíno , de Oliveira Gabriela Correia Matos , Rocha Roseanne Montargil , Vinhaes Bittencourt Alcina Maria , David Túlio Matos , Matos de Oliveira Luís 
Published: June 2024

ABSTRACTBackgroundThe association between autoantibodies and the risk of type 1 diabetes mellitus (T1DM) is well established. However, there is still a lack of quantitative insight into the role of anti-zinc transporter 8 (anti-ZnT8) antibodies and their efficacy in T1DM diagnosis.ObjectiveTo conduct a systematic review and meta-analysis on the association between anti-ZnT8 autoantibodies and the risk of T1DM.MethodsRelevant studies were retrieved from the PubMed database and analyzed using a fixed or random-effects model.ResultsOut of 211 screened articles, 23 studies were selected and a total of 14,172 patients were included in the analysis. Our pooled analysis revealed that anti-ZnT8 autoantibody expression was significantly associated with an increased risk of T1DM development in both children and adults [OR 1.14 (95% CI: 1.12-1.16); P = 0.07].ConclusionOur systematic review and meta-analysis provides robust evidence supporting a significant association between anti-ZnT8 autoantibody positivity and an increased risk of T1DM development.
nipalsMCIA: Flexible Multi-Block Dimensionality Reduction in R via Non-linear Iterative Partial Least Squares
Authors: Mattessich Max , Reyna Joaquin , Aron Edel , Ay Ferhat , Kilmer Misha , Kleinstein Steven H. , Konstorum Anna 
Published: June 2024

AbstractMotivationWith the increased reliance on multi-omics data for bulk and single cell analyses, the availability of robust approaches to perform unsupervised analysis for clustering, visualization, and feature selection is imperative. Joint dimensionality reduction methods can be applied to multi-omics datasets to derive a global sample embedding analogous to single-omic techniques such as Principal Components Analysis (PCA). Multiple co-inertia analysis (MCIA) is a method for joint dimensionality reduction that maximizes the covariance between block- and global-level embeddings. Current implementations for MCIA are not optimized for large datasets such such as those arising from single cell studies, and lack capabilities with respect to embedding new data.ResultsWe introducenipalsMCIA, an MCIA implementation that solves the objective function using an extension to Non-linear Iterative Partial Least Squares (NIPALS), and shows significant speed-up over earlier implementations that rely on eigendecompositions for single cell multi-omics data. It also removes the dependence on an eigendecomposition for calculating the variance explained, and allows users to perform out-of-sample embedding for new data.nipalsMCIAprovides users with a variety of pre-processing and parameter options, as well as ease of functionality for down-stream analysis of single-omic and global-embedding factors.AvailabilitynipalsMCIAis available as a BioConductor package athttps://bioconductor.org/packages/release/bioc/html/nipalsMCIA.html, and includes detailed documentation and application vignettes. Supplementary Materials are available online.
Spatial self-organization of cancer stem cell niches revealed by live single-cell imaging
Authors: Brulé Mathilde , Horochowska Anaïs , Fontaine Emeline , Torero-Ibad Raoul , Woesteland Flavie , Denoulte Marie , Pesez Jean , Adriaenssens Eric , Toillon Robert-Alain , Le Bourhis Xuefen , Pfeuty Benjamin , Lagadec Chann , Anquez François 
Published: June 2024

AbstractPhenotypic plasticity is a major factor of tumor heterogeneity and treatment resistance. In particular, cancer stem cells (CSCs) represent a small subpopulation within tumors with self-renewal and tumor-forming capabilities. Understanding reprogramming, maintenance, and lineage properties of CSCs requires dedicated tools to disentangle the respective influences of phenotypic inheritance and cell-cell interactions. Here we set up ultra-wide field microscopy of breast cancer cell lines expressing a stemness fluorescent reporter for several days. The fluorescent reporter distinguishes three phenotypes: cancer stem cells (CSCs), cancer differentiated cells (CDCs) and intermediate/transiting cancer cells (iCCs). Spatial statistics indicate significant zonation, aka phenotypic niches, with CSC clustering near each other but away from CDCs. Surprisingly, single cell time series reveal spontaneous reprogramming events from CDC to CSC even in unperturbed populations. We identify that such transitions are prone to arise during the cell cycle. Moreover, lineage analysis shows that the phenotype is partially inherited from ancestor cells. However, such heredity is not sufficient to explain the spatial properties of the cell population, which also depend on cell-cell interactions. Indeed, we identified that phenotypic transitions of cancer cells are influenced by the phenotypic state of neighboring cells. Reprogramming into CSCs is respectively promoted and inhibited by the presence of CSCs and CDCs in the neighborhood. Altogether, our results disentangle how phenotypic inheritance and intercellular interactions orchestrate the spatio-temporal self-organization of cancer cell heterogeneity, maintaining a subpopulation of CSCs within niches.
Development of self-healing hydrogels to support choroidal endothelial cell transplantation for the treatment of early age related macular degeneration
Authors: Pandala Narendra , Han Ian , Tobin Kevin , Brogden Nicole , Mulfaul Kelly , Mullins Robert , Tucker Budd 
Published: June 2024

AbstractIn retinal diseases such as age-related macular degeneration (AMD) and choroideremia, a key pathophysiologic step is loss of endothelial cells of the choriocapillaris, the dense vascular bed required for maintaining health and function of the retina. As such, repopulation of choroidal vasculature early in the disease process may halt disease progression. Prior studies have shown that injection of donor cells in suspension results in significant cellular efflux and poor cell survival. As such, the goal of this study was to develop a hydrogel system designed to support CEC transplantation. A library of hydrogels was synthesized using laminin (i.e., LN111, LN121, and LN421), carboxy methyl chitosan, and oxidized dextran via reversible Schiff base chemistry. Each of the developed hydrogels was readily injectable into the suprachoroidal space, with excellent gelation, mechanical, and degradation properties. Laminin-based hydrogels were compatible with immortalized CEC survival in vitro, and suprachoroidal injection of LN111 and LN121 containing gels were well-tolerated in an in vivo rat model, whereas LN421 containing gels caused significant chorioretinal inflammation. Hydrogels were detected in the suprachoroidal space of immunosuppressed rats at 1-week post-injection and were completely resorbed by 1-month post-injection. There were significantly more CECs retained in immunosuppressed rats that received cell laden hydrogels than those that received unsupported cell suspensions (i.e., CECs only). These findings pave the way for future CEC replacement studies in animal models of choroidal cell loss toward the development of future therapies.Statement of significanceAge related macular degeneration (AMD) is a leading cause of untreatable blindness in the industrial world. A key pathologic step in AMD is loss of the choriocapillaris endothelial cells, which provide vascular support to the overlying retina, including the light-sensing photoreceptors. We believe that choroidal cell replacement early in disease may prevent retinal cell death and subsequent vision loss. In this study, we present a strategy for repopulating the choriocapillaris using choroidal endothelial cell laden hydrogels. Specifically, we demonstrate the synthesis and characterization of 3 different laminin-based hydrogel systems. LN111 and LN121 hydrogels were found to increase retention of choroidal endothelial cells following suprachoroidal transplantation. These findings pave the way for future cell replacement studies in animal models of choroidal cell dropout.
Playbook Workflow Builder: Interactive Construction of Bioinformatics Workflows from a Network of Microservices
Authors: Clarke Daniel J.B. , Evangelista John Erol , Xie Zhuorui , Marino Giacomo B. , Maurya Mano R. , Srinivasan Sumana , Yu Keyang , Petrosyan Varduhi , Roth Matthew E. , Milinkov Miroslav , King Charles Hadley , Vora Jeet Kiran , Keeney Jonathon , Nemarich Christopher , Khan William , Lachmann Alexander , Ahmed Nasheath , Jenkins Sherry L. , Agris Alexandra , Pan Juncheng , Ramachandran Srinivasan , Fahy Eoin , Esquivel Emmanuel , Mihajlovic Aleksandar , Jevtic Bosko , Milinovic Vuk , Kim Sean , McNeely Patrick , Wang Tianyi , Wenger Eric , Brown Miguel A. , Sickler Alexander , Zhu Yuankun , Blood Philip D. , Taylor Deanne M. , Resnick Adam C. , Mazumder Raja , Milosavljevic Aleksandar , Subramaniam Shankar , Ma’ayan Avi 
Published: June 2024

AbstractMany biomedical research projects produce large-scale datasets that may serve as resources for the research community for hypothesis generation, facilitating diverse use cases. Towards the goal of developing infrastructure to support the findability, accessibility, interoperability, and reusability (FAIR) of biomedical digital objects and maximally extracting knowledge from data, complex queries that span across data and tools from multiple resources are currently not easily possible. By utilizing existing FAIR application programming interfaces (APIs) that serve knowledge from many repositories and bioinformatics tools, different types of complex queries and workflows can be created by using these APIs together. The Playbook Workflow Builder (PWB) is a web-based platform that facilitates interactive construction of workflows by enabling users to utilize an ever-growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem. Via a user-friendly web-based user interface (UI), workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflows are provided in reports containing textual descriptions, as well as interactive and downloadable figures and tables. To demonstrate the ability of the PWB to generate meaningful hypotheses that draw knowledge from across multiple resources, we present several use cases. For example, one of these use cases sieves novel targets for individual cancer patients using data from the GTEx, LINCS, Metabolomics, GlyGen, and the ExRNA Communication Consortium (ERCC) Common Fund (CF) Data Coordination Centers (DCCs). The workflows created with the PWB can be published and repurposed to tackle similar use cases using different inputs. The PWB platform is available from:https://playbook-workflow-builder.cloud/.
Neuroimage Denoiser - a Deep Learning Framework for Removing Noise from Transient Fluorescent Signals in Functional Imaging
Authors: Weißbach Stephan , Borghi Michela , Milkovits Jonas , Amaral Carolina , El Khallouqi Abderazzaq , Gerber Susanne , Heine Martin 
Published: June 2024

SummaryWe developed Neuroimage Denoiser, a novel U-Net-based model that effectively removes noise from microscopic recordings of transient local fluorescent signals. The model makes the denoising process independent of the recording frequency and the kinetics of the sensor used. The framework is easy to use for denoising and training and has minimal hardware requirements, thus, making it accessible for an average laboratory to create a custom version specific to their experimental setup. Neuroimage Denoiser significantly enhances the quality of functional microscopy recordings by effectively removing noise, thereby facilitating a more accurate and reliable analysis of neural activity.Highlights-Neuroimage Denoiser is a deep learning framework to remove noise from functional microscopic recordings, particularly trained and tested for glutamate imaging-Neuroimage Denoiser balances the removal of noise while preserving the amplitude of responses-Neuroimage Denoiser operates without re-training for different sensors (when the localization is similar) and recording frequenciesMotivationAccurate measurements of neuronal activity through functional imaging are critical in understanding mechanisms of synaptic plasticity and learning concerning changes in the molecular composition of single synapses. Traditional denoising methods, such as Gaussian or Median filters, indiscriminately smooth entire recordings, reducing temporal and spatial resolutions considerably. Existing frameworks are not suited to remove noise from glutamate recordings due to the fast dynamics of the sensor. Therefore, a specialized tool for the challenges imposed by glutamate recordings, i.e. faster dynamics, and synaptic localization, is needed.
SpaDE: Semantic Locality Preserving Biclustering for Neuroimaging Data
Authors: Rahaman Md Abdur , Fu Zening , Iraji Armin , Calhoun Vince 
Published: June 2024

AbstractThe most discriminative and revealing patterns in the neuroimaging population are often confined to smaller subdivisions of the samples and features. Especially in neuropsychiatric conditions, symptoms are expressed within micro subgroups of individuals and may only underly a subset of neurological mechanisms. As such, running a whole-population analysis yields suboptimal outcomes leading to reduced specificity and interpretability. Biclustering is a potential solution since subject heterogeneity makes one-dimensional clustering less effective in this realm. Yet, high dimensional sparse input space and semantically incoherent grouping of attributes make post hoc analysis challenging. Therefore, we propose a deep neural network called semantic locality preserving auto decoder (SpaDE), for unsupervised feature learning and biclustering. SpaDE produces coherent subgroups of subjects and neural features preserving semantic locality and enhancing neurobiological interpretability. Also, it regularizes for sparsity to improve representation learning. We employ SpaDE on human brain connectome collected from schizophrenia (SZ) and healthy control (HC) subjects. The model outperforms several state-of-the-art biclustering methods. Our method extracts modular neural communities showing significant (HC/SZ) group differences in distinct brain networks including visual, sensorimotor, and subcortical. Moreover, these biclustered connectivity substructures exhibit substantial relations with various cognitive measures such as attention, working memory, and visual learning.