bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic attention signaling in V4: relation to excitatory/inhibitory cell class and population coupling
Authors: Sachse Elizabeth M. , Snyder Adam C. 
Published: August 2022

AbstractNeurons have different roles in attention processing. These roles are determined by a neuron’s firing properties, neurotransmitter expression, and functional connectivity. Neurons in the visual cortical area, V4, are reliably engaged by selective attention but exhibit differences in firing rate and correlated variability. It remains unclear what specific neuronal properties shape these attention effects. We identified neurons as fast-spiking (FS) (putative inhibitory) and regular-spiking (RS) (putative excitatory) and investigated their role in anticipatory attention and how this related to their functional connectivity. V4 neurons exhibited a continuum of time-varying attention effects ranging from “restless-weak” neurons at one extreme to “quiet-strong” neurons at another. We found an interdependence between neural attention effects (e.g., restless-weak or quiet-strong), neuron type (FS, RS), and functional connectivity. In particular, we found neurons with restless-weak attention effects were more likely to be RS and have greater population coupling, compared to neurons with other types of attention effects. Also, quiet-strong neurons were more likely to be FS and these FS neurons exhibited higher spike synchrony. From this we propose that time-varying attention effects in a neuronal population depends on the relative involvement of neurons that drive stimulus processing and those that are engaged by intrinsic population activity. These results add important information to our understanding of visual attention circuits at the cellular level.
Differential patterns of taxonomic and functional diversity for two groups of canopy arthropods across spatial scales
Authors: Mahon Michael B. , Penn Hannah J. , Campbell Kaitlin U. , Crist Thomas O. 
Published: August 2022

AbstractAimArthropod diversity is often linked to variation in resource use, dispersal ability, habitat connectivity, and climate factors that differ across spatial scales. The aim of this research was to examine how species richness, functional diversity, and community composition of two taxa differing in functional roles and dispersal ability are structured across spatial scales and to identify the importance of vegetation, climate, and landscape in explaining these patterns at different scales.Location96 trees in 24 stands of 6 deciduous forest sites in 2 ecoregions of the eastern USA (North-Central Till Plain and Western Allegheny Plateau)Time period2000Major taxa studiedCanopy dwelling ants (Hymenoptera: Formicidae) and spiders (Araneae)MethodsOrganisms were collected from tree canopies using insecticidal fogging. Ant and spider taxonomic and functional beta diversity were partitioned across four hierarchical spatial scales (individual tree, forest stand, site, and ecoregion). The contribution of climactic, landscape, and vegetation variables was determined using model selection.ResultsAnt and spider species richness, functional diversity, and community composition differed between taxa and across spatial scales. Alpha diversity (within trees) was lower than expected for both taxa and types of diversity, with host tree species supporting different species of ants and spiders. While beta components of species diversity among trees and forest stands was greater than expected for both taxa, spiders also showed significant levels of beta diversity among sites. Functional beta diversity was less scale-dependent than taxonomic beta diversity. Stand-level patterns of beta diversity were significantly predicted by variation in climate and landscape connectivity.Main conclusionsEffects of climate and landscape fragmentation on the diversity and community structure of both taxa indicate that anthropogenic climate change and land use change will alter canopy arthropod communities. Results also suggest that patterns of diversity among fragmentation metrics is influenced by differences in dispersal ability.
Neuronal Maturation-dependent Nano-Neuro Interaction and Modulation
Authors: Gupta Prashant , Rathi Priya , Gupta Rohit , Baldi Harsh , Coquerel Quentin , Debnath Avishek , Derami Hamed Gholami , Raman Baranidharan , Singamaneni Srikanth 
Published: August 2022

AbstractNanotechnology-enabled neuromodulation, a rapidly growing technique, is a promising minimally-invasive tool in neuroscience and engineering for both fundamental studies as well as clinical applications. However, the nano-neuro interactions at different stages of maturation of a neural network and its implications on the nano-neuromodulation remain unclear. Here, we report heterogeneous to homogenous transformation of neuromodulation in a progressively maturing neural network. Utilizing plasmonic fluors as ultrabright fluorescent nanolabels, we reveal that negative surface charge of the nanoparticles renders selective nano-neuro interaction with a strong correlation between the maturation stage of the individual neurons in the neural network and the density of the nanoparticles bound on the neurons. In stark contrast to homogeneous neuromodulation in a mature neural network reported so far, the maturation-dependent density of the nanoparticles bound to neurons in a developing neural network resulted in a heterogeneous optical neuromodulation (i.e., simultaneous excitation and inhibition of neural network activity). This study advances our understanding of nano-neuro interactions and nano-neuromodulation with potential applications in minimally-invasive technologies for treating neuronal disorders in parts of mammalian brain where neurogenesis persists throughout aging.
Methanol fixation is the method of choice for droplet-based single-cell transcriptomics of neural cells
Authors: Gutiérrez-Franco Ana , Hassan Mohamed N. , Mularoni Loris , Plass Mireya 
Published: August 2022

AbstractSingle-cell transcriptomics methods have become very popular to study the cellular composition of organs and tissues and characterize the expression profiles of the individual cells that compose them. The main critical step in single-cell transcriptomics is sample preparation. Several methods have been developed to preserve cells after sample dissociation to uncouple sample handling from library preparation. Yet, the suitability of these methods depends on the types of cells to be processed. In this project, we perform a systematic comparison of preservation methods for droplet-based single-cell RNA-seq (scRNA-seq) on neural and glial cells derived from induced pluripotent stem cells (iPSCs) and highlight their strengths and weaknesses. We compared the cellular composition and expression profile of single-cell suspensions from fresh NPCs with that of NPCs preserved with Dimethyl Sulfoxide (DMSO), Methanol, vivoPHIX and Acetil-methanol (ACME). Our results show that while DMSO provides the highest cell quality in terms of RNA molecules and genes detected per cell, it strongly affects the cellular composition and the expression profile of the resulting datasets. In contrast, methanol fixed samples display a cellular composition like that of fresh samples while providing a good cell quality and smaller expression biases. Taken together, our results show that methanol fixation is the method of choice for performing droplet-based single-cell transcriptomics experiments on neural cell populations.
A Novel Hyper-Variable Variable Number Tandem Repeat in the Dopamine Transporter Gene (SLC6A3)
Authors: Apsley Abner T. , Domico Emma R. , Verbiest Max A. , Brogan Carly A. , Buck Evan R. , Burich Andrew J. , Cardone Kathleen M. , Stone Wesley J. , Anisimova Maria , Vandenbergh David J. 
Published: August 2022

AbstractThe dopamine transporter gene,SLC6A3, has received substantial attention in genetic association studies of various phenotypes. Although some variable number tandem repeats (VNTRs) present inSLC6A3have been tested in genetic association studies, results have not been consistent. VNTRs inSLC6A3that have not been examined genetically were characterized. Tandem Repeat Annotation Library (TRAL) was used to characterize the VNTRs of 64 unrelated long-read haplotype-phasedSLC6A3sequences. Sequence similarity of each repeat unit of the five VNTRs is reported, along with the correlations of SNP-SNP, SNP-VNTR and VNTR-VNTR alleles across the gene. One of these VNTRs is a novel hyper-VNTR (hyVNTR) in intron 8 ofSLC6A3, which contains a range of 3.4-133.4 repeat copies and has a consensus sequence length of 38bp, with 82% G+C content. The 38-base repeat was predicted to form G-quadruplexesin silicoand was confirmed by circular dichroism spectroscopy. Additionally, this hyVNTR contains multiple putative binding sites for PRDM9, which, in combination with low levels of linkage disequilibrium around the hyVNTR, suggests it might be a recombination hotspot.Summary BlurbThis VNTR has a heterozygosity value of 0.93, forms G-tetrads, and is in low linkage disequilibrium with surrounding sequence, making it a new site for genetic analysis.
Mechanistic dissection of antibody inhibition of influenza entry yields unexpected heterogeneity
Authors: Sengar Anjali , Cervantes Marcos , Kasson Peter M. 
Published: August 2022

AbstractNeutralizing antibodies against influenza have generally been classified according to their recognition sites, with antibodies against the head domain of hemagglutinin thought to inhibit attachment and antibodies against the stalk region thought to inhibit fusion. Here, we report the development of a microfluidic assay to measure neutralization of viral entry that can clearly differentiate between effects on attachment and fusion. Testing multiple broadly-neutralizing antibodies against the hemagglutinin stalk domain, we obtain a surprising result: some broadly-neutralizing antibodies inhibit fusion only, while others inhibit both fusion and viral attachment. Antibodies binding the globular head domain primarily inhibit attachment but can also reduce the fusogenic capability of viral particles that nonetheless bind receptor. These findings shed light on the unexpectedly heterogeneous mechanisms of antibody neutralization even within similar recognition sites. The assay we have developed also provides a tool to optimize vaccine design by permitting assessment of the elicited antibody response with greater mechanistic resolution.
Dynamics of transposable element accumulation in the non-recombining regions of mating-type chromosomes in anther-smut fungi
Authors: Duhamel Marine , Hood Michael E. , Rodríguez de la Vega Ricardo C. , Giraud Tatiana 
Published: August 2022

AbstractBackgroundTransposable element (TE) activity is generally deleterious to the host fitness, such that TE copies are often purged by selection, which is facilitated when meiotic recombination reshuffles variation among loci. In the absence of recombination, the number of TE insertions usually increases, but the dynamics of such TE accumulations is unknown.ResultsIn this study, we investigated the temporal dynamics of TE accumulation in the non-recombining genomic regions of 15Microbotryumspecies, leveraging on a unique dataset of 21 independent evolutionary strata of recombination cessation of different ages. We show that TEs rapidly accumulated in regions lacking recombination, but that the TE content reached a plateau at ca. 50% of occupied base pairs by 1.5 MY following recombination suppression. The same TE superfamilies have repeatedly expanded in independently evolved non-recombining regions, in particular rolling-circle replication elements (Helitrons), despite being scarce before recombination suppression. The most abundant elements, long-terminal repeat (LTR) retrotransposons of theCopiaandTy3superfamilies, expanded through transposition bursts affecting both the non-recombining regions of mating-type chromosomes and autosomes, thus suggesting that non-recombining regions constitute a reservoir of TEs that transpose to recombining regions. Based on LTR sequence divergence within and among copies, we could distinguish bursts of transposition from gene conversion.ConclusionOur study supports the TE reservoir hypothesis, by showing that TE accumulation in non-recombining has a genome-wide impact. TEs accumulated through bursts, and following a non-linear, decelerating dynamics, thus improving our knowledge on genome evolution, particularly in association with sex or mating-type chromosomes.
SUPREME: A cancer subtype prediction methodology integrating multiomics data using Graph Convolutional Neural Network
Authors: Kesimoglu Ziynet Nesibe , Bozdag Serdar 
Published: August 2022

AbstractTo pave the road towards precision medicine in cancer, patients with highly similar biology ought to be grouped into the same cancer subtypes. Utilizing high-dimensional multiomics datasets, several integrative computational approaches have been developed to uncover cancer subtypes. Recently, Graph Neural Networks (GNNs) was discovered to learn node embeddings while utilizing node features and node associations at the same time on graph-structured data. Although there are some commonly used architectures such as Graph Convolutional Network (GCN) for cancer subtype prediction, the existing prediction tools have some limitations in leveraging those architectures with multiomics integration on multiple networks. Addressing them, we developed SUPREME (asubtypepredictionmethodology) by comprehensively analyzing multiomics data and associations between patients with graph convolutions on multiple patient similarity networks. Unlike the existing tools, SUPREME generates patient embeddings from patient similarity networks, on which it utilizes all the multiomics features. In addition, SUPREME integrates all the possible combinations of embeddings with the raw multiomics features to capture the complementary signals. Extensive evaluation of all combinations makes SUPREME interpretable in terms of utilized networks and features. On three different datasets from The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), and both combined, our method significantly outperformed other integrative cancer (sub)type prediction tools and baseline methods, with overall consistent results. SUPREME-inferred subtypes had significant survival differences, mostly having more significance than ground truth (PAM50) labels, and outperformed nine cancer subtype differentiating tools and baseline methods. These results suggest that with proper utilization of multiple datatypes and patient associations, SUPREME could demystify the undiscovered characteristics in cancer subtypes that cause significant survival differences and could improve the ground truth label, which depends mainly on a single datatype. Source code for our tool is publicly available athttps://github.com/bozdaglab/SUPREME.
A single-molecule method for measuring fluorophore labeling yields for the study of membrane protein oligomerization in membranes
Authors: Ernst Melanie , Ozturk Tugba N. , Robertson Janice L. 
Published: August 2022

AbstractMembrane proteins are often structured as higher-order oligomers. Yet, the role of these specific assemblies is not always apparent, raising the question of whether differential oligomerization states can be linked to modulation of function. To better understand this hypothetical regulatory mechanism, there is an ongoing effort to quantify equilibrium reactions of membrane proteins in membranes. Single-molecule photobleaching analysis is particularly useful for this as it provides a binary readout of fluorophores attached to protein subunits at dilute conditions. The subunit capture method adds consideration of the Poisson probability of protein partitioning into liposomes from large equilibrium membranes. If the liposome size distribution is known, then the capture statistics can be modeled with accuracy to quantify oligomerization as a function of membrane density to obtain binding isotherms, as was demonstrated for the dimeric chloride/proton antiporter CLC-ec1. However, any quantification of stoichiometry also critically requires knowing the probability that a subunit is fluorescently labeled. Since labeling uncertainty is often unavoidable, we tested an alternate approach to estimate labeling yields using the photobleaching probability of an intrinsic dimeric control, the disulfide cross-linked R230C/L249C CLC-ec1. By iterative fitting of the experimental dimeric photobleaching probability distribution to a dimer model while varying labeling parameters, we predict the labeling yields measured by direct absorbance measurements of the purified protein before reconstitution. Finally, the average predicted labeling yield over multiple samples is used to estimate the dissociation constant of CLC-ec1 dimerization reactions, eliminating the need to quantify fluorophore labeling a priori. This approach can be generalized to study dimerization reactions where an irreversible dimeric control can be prepared. Thus, our study maps out a new method for quantifying fluorophore occupancy in samples that cannot be purified directly and improves quantification of membrane protein stoichiometry in membranes.
Subfunctionalization and constrained size of the immunoglobulinlociinAmbystoma mexicanum
Authors: Martinez-Barnetche J , Godoy-Lozano EE , Saint Remy-Hernández S , Pacheco-Olvera DL , Téllez-Sosa J , Valdovinos-Torres H , Pastelin-Palacios R , Mena-González H , Zambrano-Gonzalez L , López-Macías C 
Published: August 2022

AbstractBackgroundThe axolotl,Ambystoma mexicanumis a unique biological model for complete tissue regeneration. Is a neotenic endangered species and is highly susceptible to environmental stress, including infectious disease. In contrast to other amphibians, the axolotl is particularly vulnerable to certain viral infections. Like other salamanders, the axolotl genome is one of the largest (32 Gb) and the impact of genome size on Iglociarchitecture is unknown. To better understand the immune response in axolotl, we aimed to characterize the immunoglobulinlociofA. mexicanumand compare it with other model tetrapods.MethodsThe most recently published genome sequence ofA. mexicanum(V6) was used for alignment-based annotation and manual curation using previously described axolotl Ig sequences or reference sequences from other tetrapods. Gene models were further curated usingA. mexicanumspleen RNA-seq data. Human reference genomes,Xenopus tropicalis, andDanio rerio(zebrafish) were used for comparison.ResultsCanonicalA. mexicanumHeavy chain (IGH), lambda (IGL), sigma (IGS) and Surrogate light chain (SLC)lociwere identified. No kappalocuswas found. More than half of the IGHV genes and the IGHF gene are pseudogenes, there are no clan I IGHV genes and CDRH3 diversity is restricted. Although the IGHlocussize is proportional to genome size, we found local size restriction in the IGHM gene and in the V gene intergenic distances. In addition, there were V genes with abnormally large V-intron sizes, which correlated with loss of gene functionality.ConclusionTheA. mexicanumimmunoglobulinlocishare the same general genome architecture as most studied tetrapods. Consistent with its large genome, Iglociare larger; however, local size restrictions indicate evolutionary constraints likely to be imposed by high transcriptional demand of certain Ig genes, as well as the V(D)J recombination over very long genomic distance ranges. TheA. mexicanumhas undergone an extensive process of pseudogenization which partially explains a reduced potential repertoire diversity that may contribute to its impaired antibody response.
Canonical Wnt signaling regulates soft palate development through mediating ciliary homeostasis
Authors: Janečková Eva , Feng Jifan , Guo Tingwei , Han Xia , Pareek Siddhika , Ghobadi Aileen , Ho Thach-Vu , Araujo-Villalba Angelita , Alvarez Jasmine , Chai Yang 
Published: August 2022

AbstractCraniofacial morphogenesis requires complex interactions among tissues, signaling pathways, secreted factors, and organelles. The details of these interactions remain elusive. In this study, we analyzed the molecular mechanisms and homeostatic cellular activities governing soft palate development to improve regenerative strategies for cleft palate patients. We have identified canonical Wnt signaling as a key signaling pathway primarily active in cranial neural crest (CNC)-derived mesenchymal cells surrounding soft palatal myogenic cells. Using Osr2-Cre;β-cateninfl/fl mice, we further discovered that Wnt signaling is indispensable for mesenchymal cell proliferation and subsequently myogenesis through mediating ciliogenesis. Specifically, we identified that Wnt signaling directly regulates expression of the ciliary gene Ttll3 through β-catenin/Tcf7l2 complex. Impaired ciliary disassembly leads to differentiation defects of mesenchymal cells and indirectly disrupts myogenesis through decreased expression of Dlk1, a mesenchymal cell-derived pro-myogenesis factor. Moreover, we found that restoring ciliary homeostasis rescues mesenchymal cell proliferation in Osr2-Cre;β-cateninfl/fl samples. This study highlights the role of Wnt signaling in palatogenesis through controlling ciliary homeostasis, which establishes a new mechanism for Wnt-regulated craniofacial morphogenesis.
An unbiased characterization of the HLA-E and CD94/NKG2x peptide repertoire reveals peptide ligands that skew NK cell activation
Authors: Huisman Brooke D. , Guan Ning , Rückert Timo , Garner Lee , Singh Nishant K. , McMichael Andrew J. , Gillespie Geraldine M. , Romagnani Chiara , Birnbaum Michael E. 
Published: August 2022

AbstractHLA-E is a non-classical class I MHC protein involved in innate and adaptive immune recognition. While recent studies have shown HLA-E can present diverse peptides to NK cells and T cells, the HLA-E and NK receptor peptide repertoire has remained poorly defined, with only a limited number of peptide ligands identified. Here we screen a yeast-displayed peptide library in the context of HLA-E to identify 500 high-confidence unique peptides that bind both HLA-E and CD94/NKG2A or CD94/NKG2C. Utilizing the sequences identified via yeast display selections, we train prediction algorithms and identify human and cytomegalovirus (CMV) proteome-derived, HLA-E-presented peptides capable of binding and signaling through both CD94/NKG2A and CD94/NKG2C. In addition, we identify peptides which selectively activate NKG2C+ NK cells. Taken together, characterization of the HLA-E-binding peptide repertoire and identification of NK activity-modulating peptides present opportunities for studies of NK cell regulation in health and disease, in addition to vaccine and therapeutic design.