bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell label-free probing of chromatin dynamics during B lymphocyte maturation
Authors: Morrish Rikke , Yim Kevin Ho Wai , Pagliara Stefano , Palombo Francesca , Chahwan Richard , Stone Nicholas 
Published: January 2021

ABSTRACTLarge-scale intracellular signalling during developmental growth or in response to environmental alterations are largely orchestrated by chromatin within the cell nuclei. Chemical and conformational modifications of the chromatin architecture are critical steps in the regulation of differential gene expression and ultimately cell fate determination. Therefore, establishing chemical properties of the nucleus could provide key markers for phenotypic characterisation of cellular processes on a scale of individual cells.Raman microscopy is a sensitive technique that is capable of probing single cell chemical composition - and sub-cellular regions - in a label-free optical manner. As such, it has great potential in both clinical and basic research. However, perceived limitations of Raman spectroscopy such as low signal intensity and the difficulty in linking alterations in vibrational signals directly with ensuing biological effects have hampered advances in the field. Here we use immune B lymphocyte development as a model to assess chromatin and transcriptional changes using confocal Raman microscopy in combination with microfluidic devices and correlative transcriptomics, thereby linking changes in chemical and structural properties to biological outcomes. Live B lymphocytes were assessed before and after maturation. Multivariate analysis was applied to distinguish cellular components within each cell. The spectral differences between non-activated and activated B lymphocytes were then identified, and their correlation with known intracellular biological changes were assessed in comparison to conventional RNA-seq analysis. Our data shows that spectral analysis provides a powerful tool to study gene activation that can complement conventional molecular biology techniques and opens the way for mapping the dynamics in the biochemical makeup of individual cells.
Hybridization enables the fixation of selfish queen genotypes in eusocial colonies
Authors: Weyna Arthur , Romiguier Jonathan , Mullon Charles 
Published: January 2021

AbstractA eusocial colony typically consists of two main castes: queens that reproduce and sterile workers that help them. This division of labour however is vulnerable to genetic elements that favour the development of their carriers into queens. Several factors, such as intra-colonial relatedness, can modulate the spread of such caste-biasing genotypes. Here we investigate the effects of a notable yet understudied ecological setting: where larvae produced by hybridization develop into sterile workers. Using mathematical modelling, we show that the coevolution of hybridization with caste determination readily triggers an evolutionary arms race between non-hybrid larvae that increasingly develop into queens, and queens that increasingly hybridize to produce workers. Even where hybridization reduces worker function and colony fitness, this race can lead to the loss of developmental plasticity and to genetically hard-wired caste determination. Overall, our results may help understand the repeated evolution towards remarkable reproductive systems (e.g. social hybridogenesis) observed in many ant species.
The lethal triad: SARS-CoV-2 Spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of pandemic
Authors: Calcagnile Matteo , Forgez Patricia , Alifano Marco , Alifano Pietro 
Published: January 2021

AbstractVariants of SARS-CoV-2 have been identified rapidly after the beginning of pandemic. One of them, involving the spike protein and called D614G, represents a substantial percentage of currently isolated strains. While research on this variant was ongoing worldwide, on December 20th2020 the European Centre for Disease Prevention and Control reported a Threat Assessment Brief describing the emergence of a new variant of SARS-CoV-2, named B.1.1.7, harboring multiple mutations mostly affecting the Spike protein. This viral variant has been recently associated with a rapid increase in COVID-19 cases in South East England, with alarming implications for future virus transmission rates. Specifically, of the nine amino acid replacements that characterize the Spike in the emerging variant, four are found in the region between the Fusion Peptide and the RBD domain (namely the already known D614G, together with A570D, P681H, T716I), and one, N501Y, is found in the Spike Receptor Binding Domain – Receptor Binding Motif (RBD-RBM). In this study, by usingin silicobiology, we provide evidence that these amino acid replacements have dramatic effects on the interactions between SARS-CoV-2 Spike and the host ACE2 receptor or TMPRSS2, the protease that induces the fusogenic activity of Spike. Mostly, we show that these effects are strongly dependent on ACE2 and TMPRSS2 polymorphism, suggesting that dynamics of pandemics are strongly influenced not only by virus variation but also by host genetic background.
Phylogenetic analyses of SARS-CoV-2 B.1.1.7 lineage suggest a single origin followed by multiple exportation events versus convergent evolution
Authors: Vrancken B. , Dellicour S. , Smith D.M. , Chaillon A 
Published: January 2021

DisclaimerThe authors have withdrawn this manuscript because it will need to be fully actualized to properly acknowledge the contribution of several genomic data contributors, including the unique contribution of the COG-UK consortium. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding authors
Neuromodulation of Behavioral Specialization: Tachykinin Signaling Inhibits Task-specific Behavioral Responsiveness in Honeybee Workers
Authors: Han Bin , Wei Qiaohong , Wu Fan , Hu Han , Ma Chuan , Meng Lifeng , Zhang Xufeng , Feng Mao , Fang Yu , Rueppell Olav , Li Jianke 
Published: January 2021

AbstractBehavioral specialization is key to the success of social insects and often compartmentalized among colony members leading to division of labor. Response thresholds to task-specific stimuli proximally regulate behavioral specialization but their neurobiological regulation is not understood. Here, we show that response thresholds to task-relevant stimuli correspond to the specialization of three behavioral phenotypes of honeybee workers. Quantitative neuropeptidome comparisons suggest two tachykinin-related peptides (TRP2 and TRP3) as candidates for the modification of these response thresholds. Based on our characterization of their receptor binding and downstream signaling, we then confirm the functional role of tachykinins: TRP2 injection and RNAi cause consistent, opposite effects on responsiveness to task-specific stimuli of each behaviorally specialized phenotype but not to stimuli that are unrelated to their tasks. Thus, our study demonstrates that TRP-signaling regulates the degree of task-specific responsiveness of specialized honeybee workers and may control the context-specificity of behavior in animals more generally.
Differential gene expression associated with a floral scent polymorphism in the evening primroseOenothera harringtonii(Onagraceae)
Authors: Bechen Lindsey L. , Johnson Matthew G. , Broadhead Geoffrey T. , Levin Rachel A. , Overson Rick P. , Jogesh Tania , Fant Jeremie B. , Raguso Robert A. , Skogen Krissa A. , Wickett Norman J. 
Published: January 2021

AbstractBackgroundPlant volatiles play an important role in both plant-pollinator and plant-herbivore interactions. Intraspecific polymorphisms in volatile production are ubiquitous, but studies that explore underlying differential gene expression are rare.Oenothera harringtoniipopulations are polymorphic in floral emission of the monoterpene (R)-(-)-linalool; some plants emit (R)-(-)-linalool (linalool+ plants) while others do not (linalool-plants). However, the genes associated with differential production of this floral volatile inOenotheraare unknown. We used RNA-Seq to broadly characterize differential gene expression involved in (R)-(-)-linalool biosynthesis. To identify genes that may be associated with the polymorphism for this trait, we used RNA-Seq to compare gene expression in six differentOenothera harringtoniitissues from each of three linalool+ and linalool-plants.ResultsThree clusters of differentially expressed genes were enriched for terpene synthase activity: two were characterized by tissue-specific upregulation and one by upregulation only in plants with flowers that produce (R)-(-)-linalool. A molecular phylogeny of all terpene synthases identified two putative (R)-(-)-linalool synthase transcripts inOenothera harringtonii, a single allele of which is found exclusively in linalool+ plants.ConclusionsBy using a naturally occurring polymorphism and comparing different tissues, we were able to identify genes putatively involved in the biosynthesis of (R)-(-)-linalool. Expression of these genes in linalool-plants suggests a regulatory polymorphism, rather than a population-specific loss-of-function allele. Additional terpene biosynthesis-related genes that are up-regulated in plants that emit (R)-(-)-linalool may be associated with herbivore defense, suggesting a potential economy of scale between plant reproduction and defense.
Inter-domain Horizontal Gene Transfer of Nickel-binding Superoxide Dismutase
Authors: Sutherland Kevin M. , Ward Lewis M. , Colombero Chloé-Rose , Johnston David T. 
Published: January 2021

AbstractThe ability of aerobic microorganisms to regulate internal and external concentrations of the reactive oxygen species (ROS) superoxide directly influences the health and viability of cells. Superoxide dismutases (SODs) are the primary regulatory enzymes that are used by microorganisms to degrade superoxide. SOD is not one, but three separate, non-homologous enzymes that perform the same function. Thus, the evolutionary history of genes encoding for different SOD enzymes is one of convergent evolution, which reflects environmental selection brought about by an oxygenated atmosphere, changes in metal availability, and opportunistic horizontal gene transfer (HGT). In this study we examine the phylogenetic history of the protein sequence encoding for the nickel-binding metalloform of the SOD enzyme (SodN). A comparison of organismal and SodN protein phylogenetic trees reveals several instances of HGT, including multiple inter-domain transfers of thesodNgene from the bacterial domain to the archaeal domain. Nearly half of the archaeal members withsodNlive in the photic zone of the marine water column. ThesodNgene is widespread and characterized by apparent vertical gene transfer in some sediment-associated lineages within the Actinobacteriota (Actinobacteria) and Chloroflexota (Chloroflexi) phyla, suggesting the ancestralsodNlikely originated in one of these clades before expanding its taxonomic and biogeographic distribution to additional microbial groups in the surface ocean in response to decreasing iron availability. In addition to decreasing iron quotas, nickel-binding SOD has the added benefit of withstanding high reactant and product ROS concentrations without damaging the enzyme, making it particularly well suited for the modern surface ocean.
Community RNA-Seq: Multi-kingdom responses to living versus decaying root inputs in soil
Authors: Nuccio Erin E. , Nguyen Nhu H. , da Rocha Ulisses Nunes , Mayali Xavier , Bougoure Jeremy , Weber Peter , Brodie Eoin , Firestone Mary , Pett-Ridge Jennifer 
Published: January 2021

ABSTRACTRoots are the primary source of organic carbon inputs to most soils. Decomposition is a multi-trophic process involving multiple kingdoms of microbial life, but typically microbial ecology studies focus on one or two major lineages in isolation. We used Illumina shotgun RNA sequencing to conduct PCR-independent SSU rRNA community analysis (“community RNA-Seq”) to simultaneously study the bacteria, archaea, fungi, and microfauna surrounding both living and decomposing roots of the annual grass,Avena fatua. Plants were grown in13CO2-labeled microcosms amended with15N-root litter. We identified rhizosphere substrate preferences for13C-exudates versus15N-litter using NanoSIMS microarray imaging (Chip-SIP). When litter was available, rhizosphere and bulk soil had significantly more Amoebozoa, which are potentially important yet often overlooked top-down drivers of detritusphere community dynamics and nutrient cycling. Bulk soil containing litter was depleted in Actinobacteria but had significantly more Bacteroidetes and Proteobacteria. While Actinobacteria were abundant in the rhizosphere, Chip-SIP showed Actinobacteria preferentially incorporated litter relative to root exudates, indicating this group’s more prominent role in detritus elemental cycling in the rhizosphere. Our results emphasize that decomposition is a multi-trophic process involving cross-kingdom interactions, and the trajectory of carbon through this soil food web likely impacts the fate of carbon in soil.
Biodegradable and Biocompatible Graphene-based Scaffolds for Functional Neural Tissue Engineering: A Strategy Approach Using Dental Pulp Stem Cells and Biomaterials
Authors: Mansouri Negar , Al-Sarawi Said , Losic Dusan , Mazumdar Jagan , Clark Jillian , Gronthos Stan , O’Hare Doig Ryan 
Published: January 2021

AbstractNeural tissue engineering aims to restore function of nervous system tissues using biocompatible cell-seeded scaffolds. Graphene-based scaffolds combined with stem cells deserve special attention to enhance tissue regeneration in a controlled manner. However, it is believed that minor changes in scaffold biomaterial com-position, internal porous structure, and physicochemical properties can impact cellular growth and adhesion. The current work aims to investigatein vitrobiological effects of 3D graphene oxide (GO)/sodium alginate (GOSA) and reduced GOSA (RGOSA) scaffolds on dental pulp stem cells (DPSCs) in terms of cell viability and cytotoxicity. Herein, the effects of the 3D scaffolds, coating conditions, and serum supplementation on DPSCs functions are explored extensively. Biodegradation analysis revealed that addition of GO enhanced the degradation rate of composite scaffolds. Compared to the 2D surface, the cell viability of 3D scaffolds was higher (p <0.0001), highlighting the optimal initial cell adhesion to the scaffold surface and cell migration through pores. Moreover, the cytotoxicity study indicated that the incorporation of graphene supported higher DPSCs viability. It is also shown that when the mean pore size of scaffold increases, DPSCs activity decreases. In terms of coating conditions, poly-l-lysine (PLL) was the most robust coating reagent that improved cell-scaffold adherence and DPSCs metabolism activity. The cytotoxicity of GO-based scaffolds showed that DPSCs can be seeded in serum-free media without cytotoxic effects. This is critical for human translation as cellular transplants are typically serum-free. These findings suggest that proposed 3D GO-based scaffolds have favourable effects on the biological responses of DPSCs.
Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1
Authors: Li Shuang , Li Yuanyuan , Rushing Blake R. , McRitchie Susan L. , Jones Janice C. , Sumner Susan J. , Dohlman Henrik G. 
Published: January 2021

ABSTRACTG proteins were originally discovered through efforts to understand the effects of hormones, such as glucagon and epinephrine, on glucose metabolism. On the other hand, many cellular metabolites, including glucose, serve as ligands for G protein-coupled receptors. Here we investigate the consequences of glucose-mediated receptor signaling, and in particular the role of a Gα subunit Gpa2 and a non-canonical Gβ subunit, known as Asc1 in yeast and RACK1 in animals. Asc1/RACK1 is of particular interest because it has multiple, seemingly unrelated, functions in the cell. The existence of such “moonlighting” operations has complicated the determination of phenotype from genotype. Through a comparative analysis of individual gene deletion mutants, and by integrating transcriptomics and metabolomics measurements, we have determined the relative contributions of the Gα and Gβ protein subunits to glucose-initiated processes in yeast. We determined that Gpa2 is primarily involved in regulating sugar metabolism while Asc1 is primarily involved in amino acid metabolism. Both proteins are involved in regulating purine metabolism. Of the two subunits, Gpa2 regulates a greater number of gene transcripts and was particularly important in determining the amplitude of response to glucose addition. We conclude that the two G protein subunits regulate distinct but complementary processes downstream of the glucose-sensing receptor, as well as processes that lead ultimately to changes in cell growth and metabolism.AUTHOR SUMMARYDespite the societal importance of glucose fermentation in yeast, the mechanisms by which these cells detect and respond to glucose have remained obscure. Glucose detection requires a cell surface receptor coupled to a G protein that is comprised of two subunits, rather than the more typical heterotrimer: an α subunit Gpa2 and the β subunit Asc1 (or RACK1 in humans). Asc1/RACK1 also serves as a subunit of the ribosome, where it regulates the synthesis of proteins involved in glucose fermentation. This manuscript uses global metabolomics and transcriptomics to demonstrate the distinct roles of each G protein subunit in transmitting the glucose signal. Whereas Gpa2 is primarily involved in the metabolism of sugars, Asc1/RACK1 contributes to production of amino acids necessary for protein synthesis and cell division. These findings reveal the initial steps of glucose signaling and several unique and complementary functions of the G protein subunits. More broadly, the integrated approach used here is likely to guide efforts to determine the topology of complex G protein and metabolic signaling networks in humans.
Intracranial brain stimulation modulates fMRI-based network switching
Authors: Pedersen Mangor , Zalesky Andrew 
Published: January 2021

AbstractThe extent to which functional MRI (fMRI) reflects direct neuronal changes remains unknown. Using 160 simultaneous electrical stimulation (es-fMRI) and intracranial brain stimulation recordings acquired in 26 individuals with epilepsy (with varying electrode locations), we tested whether brain networks dynamically change during intracranial brain stimulation, aiming to establish whether switching between brain networks is reduced after intracranial brain stimulation. As the brain spontaneously switches between a repertoire of intrinsic functional network configurations and the rate of switching is typically increased in brain disorders, we hypothesised that intracranial stimulation would reduce the brain’s switching rate, thus potentially normalising aberrant brain network dynamics. To test this hypothesis, we quantified the rate that brain regions changed networks over time in response to brain stimulation, usingnetwork switchingapplied to multilayer modularity analysis of time-resolved es-fMRI connectivity. Network switching and synchrony was decreased after the first brain stimulation followed by a more consistent pattern of network switching over time. This change was commonly observed in cortical networks and adjacent to the electrode targets. Our results suggest that neuronal perturbation is likely to modulate large-scale brain networks, and multilayer network modelling may be used to inform the clinical efficacy of brain stimulation in epilepsy.
Structure and dynamics of semaglutide and taspoglutide bound GLP-1R-Gs complexes
Authors: Zhang Xin , Belousoff Matthew J. , Liang Yi-Lynn , Danev Radostin , Sexton Patrick M. , Wootten Denise 
Published: January 2021

SUMMARYThe glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism and appetite, and is an important target for treatment of type II diabetes and obesity. Multiple GLP-1R agonists have entered into clinical trials, such as semaglutide, progressing to approval. Others, including taspoglutide, failed through high incidence of side-effects or insufficient efficacy. GLP-1R agonists have a broad spectrum of signalling profiles. However, molecular understanding is limited by a lack of structural information on how different GLP-1R agonists engage with the GLP-1R. In this study, we determined cryo-electron microscopy (cryo-EM) structures of GLP-1R-Gs protein complexes bound with semaglutide and taspoglutide. These revealed similar peptide binding modes to that previously observed for GLP-1. However, 3D variability analysis of the cryo-EM micrographs revealed different motions within the bound peptides and the receptor relative to when GLP-1 is bound. This work provides novel insights into the molecular determinants of peptide engagement with the GLP-1R.
Modeling Oyster Reef Reproductive Sustainability: Analyzing Gamete Viability, Hydrodynamics, and Reef Structure to Facilitate Restoration ofCrassostrea virginica
Authors: Weissberg Justin , Pagano Vinny 
Published: January 2021

AbstractThe eastern oyster is a keystone species and ecosystem engineer. However, restoration efforts of wild oysters are often unsuccessful, in that they do not produce a robust population of oysters that are able to successfully reproduce. Furthermore, the dynamics of wild oyster fertilization is not yet well understood. Through conducting an experiment predicated on quantifying the influence of elementary aspects of fertilization kinetics—sperm concentration, gamete age, and success rate—we found that, as stochastic as the mating process may seem, there are correlations which fundamentally serve as the framework for assessing long-term sustainability, reef structure, and hydrodynamic parameters in relation to fertilization. We then focused on mathematically defining a procedure which simulated a concentration distribution of a single sperm and egg release where there existed conditions necessary for breeding to take place. We found a very significant impact of both gamete age and sperm concentration on fertilization rate (p < 0.0001). Our hydrodynamic model demonstrates that distance can also drastically influence broadcast spawning. This could be used as a foundation for developing a flexible model for wild oyster fertilization based on placement, initial seawater conditions, and size of the starting population. The results of this research could be implemented into a more user-friendly program which would accept multiple variables as inputs and output the probability of fertilization given arbitrary values. By accounting for environmental deviations, this generalization would increase its compatibility with the public and actualize the project’s intended purpose: enhance the planning of oyster reef restoration projects.