bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partial prevention of glucocorticoid-induced osteocyte deterioration with osteocrin gene therapy
Authors: Mazur Courtney M. , Castro Andrade Christian D. , Sato Tadatoshi , Bruce Michael , Bouxsein Mary L. , Wang Jialiang S. , Wein Marc N. 
Published: November 2021

AbstractGlucocorticoid (GC)-induced osteoporosis and subsequent bone fragility are preceded by death and dysfunction at the cellular level. In particular, short-term glucocorticoid excess suppresses osteocyte remodeling of the surrounding bone mineral, causes apoptosis of osteoblasts and osteocytes, and disrupts homeostatic bone remodeling. Preventing apoptosis and preserving osteocyte morphology and function could be effective means of preventing bone loss during glucocorticoid excess. We hypothesized that osteocrin, which preserves osteocyte viability and morphology in other models where osteocyte defects exist, could prevent osteocyte death and dysfunction in a GC excess model. We used a liver-targeted adeno-associated virus (AAV8) to induce osteocrin overexpression in mice one week prior to implantation with prednisolone or placebo pellets. After 28 days, tissues were collected for micro-CT and histological analysis. GC excess caused the expected reduction in cortical bone thickness and osteocyte canalicular length in control AAV8-treated mice, and these effects were blunted in mice overexpressing osteocrin. However, GC-induced changes in cortical porosity, trabecular bone mass, and gene expression were not prevented by osteocrin. While the mechanism of osteocrin’s effects on osteocyte morphology warrants further investigation, this study does not support a role for this model of osteocrin supplementation to combat the full skeletal effects of GC excess.
Invertebrate DNA methylation and gene regulation
Authors: Dixon Groves , Matz Mikhail 
Published: November 2021

AbstractAs human activity alters the planet, there is a pressing need to understand how organisms adapt to environmental change. Of growing interest in this area is the role of epigenetic modifications, such as DNA methylation, in tailoring gene expression to fit novel conditions. Here, we reanalyzed nine invertebrate (Anthozoa and Hexapoda) datasets to validate a key prediction of this hypothesis: changes in DNA methylation in response to some condition correlate with changes in gene expression. While we detected both differential methylation and differential expression, there was no simple relationship between these differences. Hence, if changes in DNA methylation regulate invertebrate transcription, the mechanism does not follow a simple linear relationship.
Connexinplexity: The spatial and temporal expression of connexin genes during vertebrate organogenesis
Authors: Lukowicz-Bedford Rachel M. , Farnsworth Dylan R. , Miller Adam C. 
Published: November 2021

AbstractAnimal development requires coordinated communication between cells. The Connexin family of proteins is a major contributor to intercellular communication in vertebrates by forming gap junction channels that facilitate the movement of ions, small molecules, and metabolites between cells. Additionally, individual hemichannels can provide a conduit to the extracellular space for paracrine and autocrine signaling. Connexin-mediated communication is well appreciated in epithelial, neural, and vascular development and homeostasis, and most tissues likely use this form of communication. In fact, Connexin disruptions are of major clinical significance contributing to disorders developing from all major germ layers. Despite the fact that Connexins serve as an essential mode of cellular communication, the temporal and cell-type specific expression patterns of connexin genes remain unknown in vertebrates. A major challenge is the large and complex connexin gene family. To overcome this barrier, we probed the expression of all connexins in zebrafish using single-cell RNA-sequencing of entire animals across several stages of organogenesis. Our analysis of expression patterns has revealed that few connexins are broadly expressed, but rather, most are expressed in tissue- or cell-type-specific patterns. Additionally, most tissues possess a unique combinatorial signature of connexin expression with dynamic temporal changes across the organism, tissue, and cell. Our analysis has identified new patterns for well-known connexins and assigned spatial and temporal expression to genes with no-existing information. We provide a field guide relating zebrafish and human connexin genes as a critical step towards understanding how Connexins contribute to cellular communication and development throughout vertebrate organogenesis.
Glycosaminoglycans and glycoproteins influence the elastic response of synovial fluid nanofilms on model oxide surfaces
Authors: Mann Amar S. , Smith Ariell M. , Saltzherr Joyce O. , Gopinath Arvind , Andresen Eguiluz Roberto C. 
Published: November 2021

ABSTRACTSynovial fluid (SF) is the natural lubricant found in articulated joints, providing unique cartilage surface protecting films under confinement and relative motion. While it is known that the synergistic interactions of the macromolecular constituents provide its unique load-bearing and tribological performance, it is not fully understood how two of the main constituents, glycosaminoglycans (GAGs) and glycoproteins, regulate the formation and mechanics of robust load-bearing films. Here, we present evidence that the load-bearing capabilities, rather than the tribological performance, of the formed SF films depend strongly on its components’ integrity. For this purpose, we used a combination of enzymatic treatments, quartz crystal microbalance with dissipation (QCM-D) and the surface forces apparatus (SFA) to characterize the formation and load-bearing capabilities of SF films on model oxide (i.e., silicates) surfaces. We find that, upon cleavage of proteins, the elasticity of the films is reduced and that cleaving GAGs results in irreversible (plastic) molecular re-arrangements of the film constituents when subjected to confinement. Understanding thin film mechanics of SF can provide insight into the progression of diseases, such as arthritis, but may also be applicable to the development of new implant surface treatments or new biomimetic lubricants.
Recent Urban Development Reduces Bee Abundance and Diversity
Authors: Pfeiffer Vera , Crowder David W. , Silbernagel Janet 
Published: November 2021

AbstractWild bee communities persist in cities despite major disruption of nesting and food resources by urban development. Bee diversity and abundance is key for urban agriculture and maintenance of plant diversity, and assessing what aspects of cities enhance bee populations will promote our capacity to retain and provision bee habitat. Here, we assessed how variation in land cover and neighborhood development history affected bee communities in the midwestern US urban landscape of Madison, Wisconsin. We sampled bee communities across 38 sites with relatively high (> 55%) or low (< 30%) levels of impervious surface, and assessed effects of land use and neighborhood development history on bee abundance and species richness. We show abundance and richness of bees was lower in recently developed neighborhoods, with particularly strong negative effects on soil nesting bees. Soil nesting bees and bee community richness decreased as cover of impervious surface increased, but above ground nesting bees were minimally impacted. Bee community similarity varied spatially and based on dissimilar local land cover, only for soil nesting bees, and the overall bee community. Impervious surface limited bee abundance and diversity, but new neighborhoods were associated with greater negative effects. We suggest that enhancing the structural diversity of new neighborhoods in urban ecosystems may imitate the structural benefits of older neighborhoods for bee populations.
A large scale, multiple genome comparison of acidophilic Archaea (pH ≤ 5.0) extends our understanding of oxidative stress responses in polyextreme environments
Authors: Neira Gonzalo , Vergara Eva , Cortez Diego , Holmes David S. 
Published: November 2021

AbstractAcidophilic Archaea thrive in anaerobic and aerobic low pH environments (<pH 5) rich in dissolved heavy metals that exacerbate stress caused by the production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), hydroxyl radical (•OH) and superoxide (O2•−). ROS react with lipids, proteins and nucleic acids causing oxidative stress and damage that can lead to cell death. Herein, genes and mechanisms potentially involved in ROS mitigation are predicted in over 200 genomes of acidophilic Archaea with sequenced genomes. These organisms can be subjected to simultaneous multiple stresses such as high temperature, high salinity, low pH and high heavy metal loads. Some of the topics addressed include: (1) the phylogenomic distribution of these genes and what can this tell us about the evolution of these mechanisms in acidophilic Archaea; (2) key differences in genes and mechanisms used by acidophilic versus non-acidophilic Archaea and between acidophilic Archaea and acidophilic Bacteria and (3) how comparative genomic analysis predicts novel genes or pathways involved in oxidative stress responses in Archaea and possible Horizontal Gene Transfer (HGT) events.
T cell-intrinsic vitamin A metabolism and its signaling are targets for memory T cell-based cancer immunotherapy
Authors: Fujiki Fumihiro , Morimoto Soyoko , Katsuhara Akiko , Okuda Akane , Ogawa Saeka , Ueda Eriko , Miyazaki Maki , Isotani Ayako , Ikawa Masahito , Nishida Sumiyuki , Nakajima Hiroko , Tsuboi Akihiro , Oka Yoshihiro , Nakata Jun , Hosen Naoki , Kumanogoh Atsushi , Oji Yusuke , Sugiyama Haruo 
Published: November 2021

AbstractMemory T cells play an essential role in infectious and tumor immunity. Vitamin A metabolites such as retinoic acid are immune modulators, but the role of vitamin A metabolism in memory T- cell differentiation is unclear. In this study, we identified retinol dehydrogenase 10 (Rdh10), which metabolizes vitamin A to retinal (RAL), as a key molecule for regulating T cell differentiation. T cell-specific Rdh10 deficiency enhanced memory T-cell formation through blocking RAL production in infection model. Epigenetic profiling revealed that retinoic acid receptor (RAR) signaling activated by vitamin A metabolites induced comprehensive epigenetic repression of memory T cell-associated genes, including TCF7, thereby promoting effector T-cell differentiation. Importantly, memory T cells generated by Rdh10 deficiency and blocking RAR signaling elicited potent anti-tumor responses in adoptive T-cell transfer setting. Thus, T cell differentiation is regulated by vitamin A metabolism and its signaling, which should be novel targets for memory T cell-based cancer immunotherapy.
Photostimulation of VTA-IC dopaminergic inputs enhances the salience to consolidate aversive taste recognition memory via D1 receptors
Authors: Gil-Lievana E. , Ramírez-Mejía G. , Urrego-Morales O. , Luis-Islas J. , Gutierrez Ranier. , Bermúdez-Rattoni F. 
Published: November 2021

AbstractTaste memory involves storing information through plasticity changes in the neural network of taste, including the insular cortex (IC) and ventral tegmental area (VTA), a critical provider of dopamine. Although a VTA-IC dopaminergic pathway has been demonstrated, its role to consolidate taste recognition memory remains poorly understood. We found that photostimulation of dopaminergic neurons in the VTA or VTA-IC dopaminergic terminals of TH-Cre mice increases the salience of a novel taste stimulus regardless of its hedonic value, without altering their taste palatability. Importantly, the inhibition of the D1-like receptor into the IC impairs the salience to facilitate consolidation of an aversive taste recognition memory. Finally, our results showed that VTA photostimulation improves the salience to consolidate a conditioned taste aversion memory through the D1-like receptor into the IC. It is concluded that the dopamine activity from the VTA into IC is required to increase the salience enabling the consolidation of a taste recognition memory. Notably, the D1-like receptor activity into the IC is required to consolidate both innate and learned aversive taste memories but not appetitive taste memory.
The global spread and invasion capacities of alien ants
Authors: Wong Mark K. L. , Economo Evan P. , Guénard Benoit 
Published: November 2021

AbstractThe ecological and economic impacts of biological invasions are usually highly conspicuous, but these are the outcome of a global, multistage process that is obscured from view. For most taxa, we lack a large-scale picture of the movements of alien species, the biases and barriers that promote or inhibit their spread at each stage, and blind spots in our ability to detect species during their spread. For instance, countries rely heavily on customs interceptions to prevent new species introductions, but their efficacy for detecting invaders remains unclear. To address these gaps, we synthesize and provide data at unprecedented geographic resolution on the global diversity and distribution of alien ants, a pervasive group strongly impacting humans and ecosystems. From >145,000 records spanning 602 regions, we identify 522 ant species exhibiting human-mediated spread, doubling recent estimates of their diversity. We show that movements of alien ant species across regions globally are non-random and, moreover, that these flows differ by the extents to which species invade—ranging from arrival to indoor establishment, naturalization, and harmful status. Importantly, we find that almost two-thirds of the 309 species that naturalize globally—most of which are ground- and litter-dwelling—are absent from customs interceptions, which record disproportionately high numbers of arboreal species. Our results illustrate the vast, yet uneven extent of ant invasions globally, and suggest that most alien species bypass biosecurity controls while spreading successfully worldwide. This raises doubts on the efficacy of current customs interceptions procedures and highlights a need for radically new approaches.Significance statementBiological invasions impact humans and ecosystems tremendously. Invasions are difficult to address because little is known about large-scale patterns of spread, species’ capacities to invade ecosystems, and the efficacy of existing biosecurity measures. This paper tackles these issues for alien ants, one of the most damaging groups of invasive animals. An unprecedented dataset reveals that 522 ant species exhibit human-mediated spread, 270 more than previously known. Species are grouped under four levels of invasion capacity corresponding to different invasion barriers. Geographic sources and sinks for the groups differ globally. Two-thirds of species with naturalization capacity have never been recorded at customs interceptions, which fail to detect many litter-dwelling species. Novel detection and control strategies for inconspicuous alien organisms are needed.
Factors affecting virus prevalence in honey bees in the Pacific-Northwest, USA
Authors: Pfeiffer Vera W , Crowder David W 
Published: November 2021

AbstractGlobal efforts to assess honey bee health show viruses are major stressors that undermine colony performance. Identifying factors that affect virus incidence, such as management practices and landscape context, could aid in slowing virus transmission. Here we surveyed viruses in honey bees from 86 sites in the Pacific Northwest, USA, and tested effects of regional bee density, movement associated with commercial pollination, julian date, and hive management on virus prevalence. We also explored patterns of virus co-occurrence and spatial autocorrelation to identify whether local transmission was a primary driver of pathogen distribution. Our surveys found widespread prevalence of Deformed wing virus (DWV), Sacbrood virus (SBV), and Black queen cell virus (BQCV). BQCV and SBV were most prolific in commercial apiaries, while Chronic bee paralysis virus (CPBV) was more common in hobbyist apiaries than commercial apiaries. DWV was most common in urban landscapes and was best predicted by mite prevalence and julian date, while the incidence of both SBV and BQCV were best predicted by regional apiary density. We did not find evidence of additional spatial autocorrelation for any viruses, although high co-occurrence suggests parallel transmission patterns. Our results support the importance of mite management in slowing virus spread and suggest that greater bee density increases transmission. Our study provides support that viruses are widespread in honey bees and connects known mechanisms of virus transmission to the distribution of pathogens observed across the Pacific Northwest.HighlightsThree viruses were widespread in honey bee populations across the Pacific Northwest, USABlack queen cell and Sacbrood viruses were most common in high density hivesDeformed wing virus was most common in hives that had high mite loadsThe presence of many viruses in bees suggests parallel or synergistic transmission
Disorder in Ca2+ Release Unit Locations Confers Robustness but Cuts Flexibility of Heart Pacemaking
Authors: Maltsev Anna V. , Maltsev Victor A. 
Published: November 2021

AbstractExcitation-contraction coupling kinetics are dictated by the rate and rhythm of the excitations generated by sinoatrial-nodal cells. These cells generate local Ca releases (LCRs) that activate Na/Ca exchanger current, which accelerates diastolic depolarization and determines the rate and rhythm of the excitations. The LCRs are generated by clusters of ryanodine receptors, Ca release units (CRUs), residing in the sarcoplasmic reticulum. While the spatial CRU distribution in pacemaker cells exhibits substantial heterogeneity, it remains unknown if it has any functional importance. Using numerical modeling, here we showed that with a square lattice distribution of CRUs, Ca-induced-Ca-release propagation during diastolic depolarization is insufficient for pacemaking within a broad lower range of realistic ICaL densities. Allowing each CRU to deviate from its original lattice position fundamentally changes the model behavior: during diastolic depolarization sparks propagate, forming LCRs observed experimentally. As disorder in the CRU positions increases, the CRU distribution exhibits larger empty spaces but simultaneously CRU clusters, as in Poisson clumping. Propagating within the clusters, Ca release becomes synchronized, increasing AP firing rate and reviving pacemaker function within lower ICaL densities at which cells with lattice CRU distribution were dormant/non-firing. However, cells with fully disordered CRU positions cannot reach low firing rates and their β-adrenergic receptor stimulation effect was substantially decreased. Thus, order/disorder in CRU locations regulates Ca release propagation and could be harnessed by pacemaker cells to regulate their function. Excessive disorder is expected to limit heart rate range that may contribute to heart rate range decline with age and in disease.SummaryThe present numerical modeling study shows that disorder in locations of Ca release units in cardiac pacemaker cells has substantial functional impact by creating release clusters, similar to Poisson clumping, and opportunity of Ca release to propagate within the clusters.
Genetic mapping of genotype-by-ploidy effects in Arabidopsis thaliana
Authors: Wijnen Cris L. , Becker Frank F.M. , Okkersen Andries A. , de Snoo C. Bastiaan , Boer Martin P. , van Eeuwijk Fred A. , Wijnker Erik , Keurentjes Joost J.B. 
Published: November 2021

AbstractPlants can express different phenotypic responses following polyploidization, but ploidy-dependent phenotypic variation has so far not been assigned to specific genetic factors. To map such effects, segregating populations at different ploidy levels are required. The availability of an efficient haploid-inducer line in Arabidopsis thaliana allows for the rapid development of large populations of segregating haploid offspring. Because Arabidopsis haploids can be self-fertilised to give rise to homozygous doubled haploids, the same genotypes can be phenotyped at both the haploid and diploid ploidy level. Here, we compared the phenotypes of recombinant haploid and diploid offspring derived from a cross between two late flowering accessions to map genotype x ploidy (GxP) interactions. Ploidy-specific quantitative trait loci (QTLs) were detected at both ploidy levels. This implies that mapping power will increase when phenotypic measurements of monoploids are included in QTL analyses. A multi-trait analysis further revealed pleiotropic effects for a number of the ploidy specific QTLs as well as opposite effects at different ploidy levels for general QTLs. Taken together, we provide evidence of genetic variation between different Arabidopsis accessions being causal for dissimilarities in phenotypic responses to altered ploidy levels, revealing a GxP effect. Additionally, by investigating a population derived from late flowering accessions we revealed a major vernalisation specific QTL for variation in flowering time, countering the historical bias of research in early flowering accessions.
Mosaic loss of chromosome Y in aged human microglia
Authors: Vermeulen Michael C. , Pearse Richard , Young-Pearse Tracy , Mostafavi Sara 
Published: November 2021

AbstractMosaic loss of chromosome Y (LOY) is a particularly common acquired structural mutation in the leukocytes of aging men and it has been shown to correlate with several age-related diseases including Alzheimer’s disease (AD). To derive the molecular basis of LOY in brain cells, we create an integrated resource by aggregating data from 21 single-cell and single-nuclei RNA brain studies, yielding 763,410 cells to investigate the presence and cell-type specific burden of LOY. We created robust quantification metrics for assessing LOY, which were validated using a multi-modal dataset. Using this new resource and LOY-quantification approach, we found that LOY frequencies differed widely between CNS cell-types and individual donors. Among five common neural cell types, microglia were most affected by LOY (7.79%, n=41,949), while LOY in neurons was rare (0.48%, n=220,010). Differential gene expression analysis in microglia found 188 autosomal genes, 6 X-linked genes, and 11 pseudoautosomal genes, pointing to broad dysregulation in lipoprotein metabolism, inflammatory response, and antigen processing that coincides with loss of Y. To our knowledge, we provide the first evidence of LOY in the microglia, and highlight its potential roles in aging and the pathogenesis of neurodegenerative disorders such as AD.
Monocarboxylate Transporter 1 (MCT1) mediates succinate export in the retina
Authors: Bisbach Celia M. , Hass Daniel T. , Hurley James B. 
Published: November 2021

AbstractPurposeSuccinate is exported by the retina and imported by eyecup tissue. The transporter(s) mediating this process have not yet been identified. Recent studies showed that Monocarboxylate Transporter 1 (MCT1) can transport succinate across plasma membranes in cardiac and skeletal muscle. Retina and retinal pigment epithelium (RPE) both express multiple MCT isoforms including MCT1. We tested the hypothesis that MCTs facilitate retinal succinate export and RPE succinate import.MethodsWe assessed retinal succinate export and eyecup succinate import in short term ex vivo culture using gas chromatography-mass spectrometry. We test the dependence of succinate export and import on pH, proton ionophores, conventional MCT substrates, and the MCT inhibitors AZD3965, AR-C155858, and diclofenac.ResultsSuccinate exits retinal tissue through MCT1 but does not enter RPE through MCT1 or any other MCT. Intracellular succinate levels are a contributing factor that determines if an MCT1-expressing tissue will export succinate.ConclusionsMCT1 facilitates export of succinate from retinas. An unidentified, non-MCT transporter facilitates import of succinate into RPE.