bluuebunny/crossref_metadata_2025_split huggingface dataset:
On an Analogy Between Ephaptic Coupling in Large Tracts and Cross-Modal Integration During Illusory Percept
Authors: Chawla Aman , Morgera Salvatore Domenic 
Published: October 2022

AbstractIn this paper, the authors report simulations analogous to cross-modal integration which can be modeled by thinking of large (in terms of numbers of axons) axon tracts with distinctly demarcated subsets of axons. In such a tract, when the demarcated regions are separately stimulated they fire in response to the stimulation. Due to extracellular current-based coupling, at a later time, unstimulated axons also begin to cross-talk. The simulation graphical result, though on a faster time scale, is analogous to the multi-channel MEG recordings of “AV-(A+V)” obtained by Shams et. al. When the coupling parameter is weakened, this cross-talk disappears. In Shams et. al., the appearance and disappearance of cross-talk are related to the perception of an illusory flash by the subject. Our extrapolated conclusion is that ephaptic coupling might be a part of the mechanism for cross-talk between brain regions mediating, say, audio and visual-processing. We also study noisy ephaptic coupling and additionally do a comparative study with the Kuramoto model, which yields insight into the exact and detailed mechanism of ephaptic synchronization.
Endothelial cells release microvesicles that harbor multivesicular bodies and secrete exosomes
Authors: Petersen Jennifer D. , Mekhedov Elena , Kaur Sukhbir , Roberts David D. , Zimmerberg Joshua 
Published: October 2022

ABSTRACTExtracellular vesicles (EVs) released by resting endothelial cells support vascular homeostasis. To better understand endothelial cell EV biogenesis, we examined cultured human umbilical vein endothelial cells (HUVECs) prepared by rapid freezing, freeze-substitution, and serial thin section electron microscopy. Thin sections of HUVECs revealed clusters of membrane protrusions on the otherwise smooth cell surface. The protrusions contained membrane-bound organelles, including multivesicular bodies (MVBs), and appeared to be on the verge of pinching off to form microvesicles. Beyond cell peripheries, membrane-bound vesicles with internal MVBs were observed, and serial sections confirmed that they were not connected to cells. These observations are consistent with the notion that these multi-compartmented microvesicles (MCMVs) pinch-off from protrusions. Remarkably, omega figures formed by fusion of MVBs with the MCMV limiting membrane were directly observed, apparently caught in the act of releasing exosomes from the MCMV. In summary, MCMVs are a novel form of EV that bud from membrane protrusions on the HUVEC surface, contain MVBs and release exosomes. These observations suggest that exosomes can be harbored within and released from transiting microvesicles after departure from the parent cell, constituting a new site of exosome biogenesis occurring from endothelial and potentially additional cell types.
Spatially coordinated collective phosphorylation filters spatiotemporal noises for precise circadian timekeeping
Authors: Chae Seok Joo , Kim Dae Wook , Lee Seunggyu , Kim Jae Kyoung 
Published: October 2022

SummaryThe circadian (∼24h) clock is based on a negative feedback loop centered around the PERIOD protein (PER), translated in the cytoplasm and then enters the nucleus to repress its own transcription at the right time of day. Such precise nucleus entry is mysterious because thousands of PER molecules transit through crowded cytoplasm and arrive at the perinucleus across several hours. To understand this, we developed a mathematical model describing the complex spatiotemporal dynamics of PER as a single random time delay. We find that the spatially coordinated bistable phosphoswitch of PER, which triggers the phosphorylation of accumulated PER at the perinucleus, leads to the synchronous and precise nuclear entry of PER. This leads to robust circadian rhythms even when PER arrival times are heterogenous and perturbed due to changes in cell crowdedness, cell size, and transcriptional activator levels. This shows how the circadian clock compensates for spatiotemporal noise.Graphical AbstractHighlightsThe time window when PER protein arrives at the perinucleus is wide and keeps changing.A bistable phosphoswitch enables precise nuclear entry of PER protein.This leads to robust circadian rhythms when cell congestion level and size change.This describes how the circadian clock compensates for spatiotemporal noise.
Translesion DNA synthesis polymerase κ is essential to a carcinogen-induced nucleolar stress response
Authors: Paul Shilpi , Rebok Abbey , Cifani Paolo , Paul Anirban , Pappin Darryl , Huang Tony T. , Spratt Thomas E. 
Published: October 2022

AbstractDNA polymerase kappa (Polκ) has multiple cellular roles such as translesion DNA synthesis, replication of repetitive sequences and nucleotide excision repair. However, the mechanisms regulating Polκ’s cellular activities are unknown. Since all polymerases insert the canonical deoxynucleotide triphosphates, it is difficult to determine which polymerase is active at a particular genomic site. To counter this difficulty, we utilized the selective Polκ substrate,N2-(4-ethynylbenyl)-2’-deoxyguanosine (EBndG), as bait to capture proteins associated with Polκ synthesized DNA. Here we show that, Polκ is active in the nucleolus and Polκ synthesized DNA are enriched with nucleolar proteins. Exposure of cells to benzo[a]pyrene diol epoxide (BPDE) induced hallmarks of nucleolar stress, increased Polκ stability and nucleolar activity. Other agents that induce nucleolar stress such as mitomycin C, cisplatin and actinomycin D also increased Polκ’s nucleolar activity. The Polκ activity was cell-cycle independent and dependent on PCNA ubiquitination. In addition, we identified that the expression and activity of Polκ is regulated by the polycomb complex protein Ring Finger Protein 2 (RNF2) and by poly(ADP)-ribose polymerase 1 (PARP1) catalyzed PARylation. This study provides insight into the novel role of Polκ in ribosomal RNA synthesis, in maintaining ribosomal DNA integrity after DNA damage thus protecting the cells from nucleolar stress.
Consistent differences in eggshell phenotypes select for bluer eggs in an avian host-parasite system
Authors: Villa Juliana , Wisocki Phillip , Dela Cruz Jacob E. , Hanley Daniel 
Published: October 2022

AbstractAvian brood parasitism is a well-recognized model for studying coevolution. In this model, hosts adapt the ability to recognize and remove parasitic young to avoid the costs of rearing foreign offspring, while parasites counter-adapt phenotypes to evade detection. A classic example of host-parasite coevolutionary arms race is the great reed warbler and its parasite the common cuckoo (hereafter ‘warbler’ and ‘cuckoo’, respectively). Recent work has found that cuckoo eggs are more likely to be accepted by warblers when those are bluer than their own eggs. Therefore, hosts would select for bluer cuckoo eggs; in turn, this provides directional selection for hosts eggs to remain bluer than cuckoo eggs. Here, we tested whether there were consistent differences in eggshell appearance between cuckoo and warbler eggs using a dataset which provides eggshell coloration of both warblers and cuckoos from the same nest. Despite being a textbook example of mimicry, we found that the cuckoos have significantly browner eggs than the warblers. These findings most likely suggest that this warbler-cuckoo system is experiencing negative frequency-dependent selection, as expected under red queen dynamics. Future research comparing warbler-cuckoo interactions over time would advance our understanding of the coevolution between avian brood parasites and their hosts.
Direct activation of the Ras-Akt network mediates polarity and organizes protrusions in human neutrophil migration
Authors: Pal Dhiman Sankar , Banerjee Tatsat , Lin Yiyan , Borleis Jane , Devreotes Peter N. 
Published: October 2022

AbstractFunctions of Ras oncogenes and their downstream effectors are typically associated with cell proliferation and growth control while their role in immune cell migration has been largely unexplored. Although Ras-mediated signaling cascades have been implicated in immune response, there is no conclusive evidence to show local activation of these pathways on the plasma membrane directly regulates cell motility or polarity. Using spatiotemporally precise, cryptochrome-based optogenetic systems in human neutrophils, we abruptly altered protrusive activity, bypassing the chemoattractant-sensing receptor/G-protein network. First, global recruitment of active KRas4B/HRas isoforms or the guanine nucleotide exchange factor, RasGRP4, immediately increased spreading and random motility in neutrophils. Second, creating Ras activity at the cell rear generated new protrusions at the site and reversed pre-existing polarity, similar to the effects of steep chemoattractant gradients. Third, recruiting GTPase activating protein, RASAL3, at cell fronts abrogated existing protrusions and changed the direction of motility whereas dynamically inhibiting nascent fronts stopped migration completely. Fourth, combining pharmacological inhibition studies with optogenetics revealed that mTorC2 is more important than PI3K for Ras-mediated polarity and migration. Finally, local recruitment of Ras-mTorC2 effector, Akt, also generated new protrusions, rearranged pre-existing polarity, and triggered migration, even in absence of PI3K signaling. We propose that actin assembly, cell shape, and migration modes in immune cells are promptly controlled by rapid, local activities of established components of classical growth-control pathways independently of receptor activation.
Gut microbiota assemblages of generalist predators are driven by local- and landscape-scale factors
Authors: Saqib Hafiz Sohaib Ahmed , Sun Linyang , Pozsgai Gabor , Liang Pingping , Goraya Mohsan Ullah , Akutse Komivi Senyo , You Minsheng , Gurr Geoff M. , You Shijun 
Published: October 2022

AbstractThe gut microbiomes of arthropods are reported to have significant impact on key physiological functions such as nutrition, reproduction, behavior, and health. Spiders are diverse and numerically dominant predators in crop fields where they are potentially important regulators of pests. The taxonomic structure of spider gut microbiomes, and environmental drivers of composition are unknown. Harnessing spiders to support agricultural productivity is likely to be supported by an understanding of the gut microbiomes of these predators. This study aimed to deciphering the gut microbiome assembly of predators as well as elucidating the potential implications of key environmental constraints in this process. Here, we used high-throughput sequencing to examine for the first time how the assemblages of bacteria in the gut of spiders are shaped by diverse environmental variables. A total of 27 bacterial phyla were detected with Proteobacteria and Firmicutes dominant. The core bacterial communities included the families Enterobacteriaceae, Chloroplast, Lactobacillaceae, Pseudomonadaceae, Lachnospiraceae, Leuconostocaceae and Ruminococcaceae. Local drivers of microbiome composition were the globally-relevant input use system (organic production versus conventional practice), and crop identity (Chinese cabbage versus cauliflower). Landscape-scale factors, proportion of forest and grassland, compositional diversity, and habitat edge density, also strongly affected gut microbiota. Specific bacterial taxa were enriched in the gut of spiders sampled from different settings and seasons. These findings provide a comprehensive insight into the composition and plasticity of spider gut microbiota. Understanding the temporal responses of specific microbiota could lead to innovative strategies development for boosting biological control services of predators.
MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via Protein Kinase C
Authors: Segui-Perez Celia , Stapels Daphne A.C. , Ma Ziliang , Su Jinyi , Passchier Elsemieke , Westendorp Bart , Wu Wei , van Putten Jos P.M. , Strijbis Karin 
Published: October 2022

AbstractRegulation and adaptation of intestinal epithelial barrier function is essential for human health. The transmembrane mucin MUC13 is an abundant intestinal glycoprotein with important functions for mucosal maintenance that are not yet completely understood. We demonstrate that in intestinal epithelial monolayers MUC13 localized to both the apical surface and the tight junction (TJ) region on the lateral membrane. MUC13 deletion resulted in increased transepithelial resistance (TEER) and reduced translocation of small solutes. TJ proteins including claudins and occludin were highly increased in membrane fractions of MUC13 knockout cells. Removal of the MUC13 cytoplasmic tail (CT) also altered TJ composition but did not result in increased TEER. The increased buildup of TJ complexes in ΔMUC13 and MUC13-ΔCT cells was dependent on PKC, which is in line with a predicted PKC motif in the MUC13 cytoplasmic tail. The responsible PKC member might be PKCδ based on elevated protein levels in the absence of MUC13. Our results identify MUC13 as a central player in TJ complex stability and intestinal barrier permeability.
Lipid homeostasis is essential for a maximal ER stress response
Authors: Garcia Gilberto , Zhang Hanlin , Moreno Sophia , Kimberly Tsui C. , Webster Brant Michael , Higuchi-Sanabria Ryo , Dillin Andrew 
Published: October 2022

AbstractChanges in lipid metabolism are associated with aging and age-related diseases, including proteopathies. The endoplasmic reticulum (ER) is uniquely a major hub for protein and lipid synthesis, making its function essential for both protein and lipid homeostasis. However, it is less clear how lipid metabolism and protein quality may impact each other. Here, we identitylet-767, a putative hydroxysteroid dehydrogenase, as an essential gene for both lipid and ER protein homeostasis. Knockdown oflet-767reduces lipid stores, alters ER morphology in a lipid-dependent manner, and also blocks induction of the Unfolded Protein Response of the ER (UPRER). Interestingly, a global reduction in lipogenic pathways restores UPRERinduction in animals with reducedlet-767. Specifically, we find that supplementation of 3-oxoacyl, the predicted metabolite directly upstream oflet-767, is sufficient to block induction of the UPRER. This study highlights a novel interaction through which changes in lipid metabolism can alter a cell’s response to protein-induced stress.
Carryover effects of tire wear particle leachate threats reproduction across multiple generations
Authors: Chai Yanchao , Wang Haiqing , Lv Mengru , Yang Jiaxin 
Published: October 2022

AbstractToxic additives leached from tire wear particle (TWP) have been linked to some collective death events of fish, also impose impacts on zooplankton as secondary consumer in aquatic food web. In addition to direct impacts of TWP leachate at the current generation, potential delayed carryover from past exposure across multi-generational lineage may augment impacts on individual reproduction, then population maintenance. We investigated the carryover effects from persistent exposure and past TWP leachate exposure along generation passaging on the individual reproduction of rotifer,Brachionus calyciflorus, a typical zooplankton. For rotifer treated with TWP leachate across continuous 7 generations, their offspring were divided into parental exposure or no exposure in each generation. And rotifer transferred into no exposure were maintained for 3 generations to eliminate indirect exposure through their parental germ. The similar response of reproduction, via carryover effects from parental exposure, also emerged in offspring without exposure. Persistent exposure across multiple generations additively impaired individual reproduction performance by transferring from its hermetic effects in original generation, even caused final population collapse. TWP leachate could impose cascading toxicity on population persistence of zooplankton via carryover and cumulative effects on reproduction for long term, which must be considered in risk assessment and management policy to alleviate the effects of TWP.
Tell me who your neighbors are: The role of spatial location and tree species identity in determining the ectomycorrhizal community composition of saplings and mature trees in a mixed conifer forest
Authors: Livne-Luzon Stav , Avidar Mor , Herol Lior , Rog Ido , Klein Tamir , Shemesh Hagai 
Published: October 2022

AbstractThe mutualistic interaction between trees and ectomycorrhizal fungi (EMF) can have a major effect on forest dynamics and specifically in seedling establishment. Both intrinsic (i.e., identity of the sapling) and extrinsic (i.e., the identity of mature trees in the vicinity of the sapling) factors can affect the EMF community composition of young saplings.Here, we compared the EMF community composition associated with the roots of young saplings and mature trees of two co-habiting Pinaceae:Pinus halepensisandCedrus deodaragrowing together in a planted forest plot, using fungal ITS metabarcoding.We found that the differences between the two sapling groups were mostly attributed to changes in the relative abundance of specific fungal species. Moreover, we found that physical proximity to a specific host species had a significant effect on the community composition of young saplings. However, while no significant differences in sapling size were apparent, the sapling shoot structure was affected by the identity of the nearest mature tree and its unique EMF community composition.Synthesis: These results suggest that the dynamics of the EMF community are greatly determined by extrinsic factors such as the small-scale distribution of mature trees in the forest, with possible cascading effects on the development of young trees.
RIG-I activation primes and trains innate antiviral immune memory
Authors: Adamson Maike S , Nesic Svetozar , Buness Andreas , Bayrak Kübra , Schmitz Saskia , Soler Sofía , Zillinger Thomas , Marx Samira , Lambing Silke , Andryka-Cegielski Katarzyna , Khan Fawad , Schlee-Guimarães Thais M. , Herberhold Stephan , Proietti Michele , Placek Katarzyna , Reading Patrick , Cicin-Sain Luca , Schlee Martin , van den Boorn Jasper , Hartmann Evelyn , Hartmann Gunther , Bartok Eva 
Published: October 2022

AbstractAdaptive processes of the innate immune system, known as trained immunity (TI), are critical to human health and disease, yet they have not been systematically investigated downstream of antiviral sensing. Here, we elucidate the potential of the antiviral cytosolic RNA receptor retinoic acid-inducible gene I (RIG-I) to train, prime and tolerize the innate immune system. Using a specific RIG-I agonist, we observed that repetitive stimulation enhanced interferon-stimulated gene (ISG) and pro-inflammatory cytokine induction in human primary monocytes, epithelial cells and fibroblasts and afforded non-specific antiviral protection. RNA sequencing revealed broad, cell type-specific transcriptional changes, indicative of priming of ISGs and training of the NFκB pathway, without measurable tolerization, while ATAC sequencing in monocytes demonstrated chromatin remodeling and enhanced accessibility of key transcription factor-binding motifs such as STAT1. Moreover, while STAT1 signaling was critically required, it was not sufficient to recapitulate RIG-I induced TI. Altogether, our data demonstrate that RIG-I-mediated TI promotes an immunologically alert state with important implications for host defense and the application of RIG-I ligands in anti-infective and anti-tumoral therapies.One Sentence SummaryRIG-I activation trains and primes innate immune response at the cellular level, affording non-specific immune protection by immune and non-immune cells.
Changes in protein dynamical parameters derived from quasi-elastic neutron scattering spectra induced by coherent scattering: A molecular dynamics simulation study
Authors: Matsuo Tatsuhito 
Published: October 2022

AbstractProtein dynamics at the sub-nanosecond timescale and the Å length-scale has widely been studied using quasi-elastic neutron scattering (QENS). In almost all QENS studies on hydrogenated proteins in D2O buffers, analysis of the spectra after buffer subtraction is carried out under the assumption that the remaining spectra arise from incoherent scattering of proteins while the contribution of coherent scattering is negligible. On the contrary, a study using polarization analysis has shown that the coherent scattering accounts for more than 10% of the total scattering intensity of hydrogenated proteins (Gaspar et al., Biochim. Biophys. Acta 1804:76–82 (2010)). In addition, the effects of coherent scattering on the values of dynamical parameters of proteins obtained by analysis of QENS spectra remain unclear. Here, molecular dynamics (MD) simulation on hen egg white lysozyme was used to investigate this issue. QENS spectra containing only incoherent scattering and those containing both incoherent and coherent scattering were calculated from the MD trajectory. Dynamical parameters were then extracted from the two simulated QENS spectra. Comparison of the resultant dynamical parameters has shown that the error in the values of the dynamical parameters induced by coherent scattering is at most 6%. This error is unlikely to significantly affect the results of QENS studies that investigate the relative changes in protein dynamics caused by different physicochemical conditions such as temperature unless dynamical parameters need to be determined with high precision at the absolute scale.
Randomly incorporated genomic 6mA delays zygotic transcription initiation
Authors: Febrimarsa  , Gornik Sebastian G , Barreira Sofia N , Salinas-Saavedra Miguel , Schnitzler Christine E , Baxevanis Andreas D , Frank Uri 
Published: October 2022

SUMMARYN6-methyldeoxyadenosine (6mA) is a chemical alteration of DNA, observed across all realms of life. The functions of 6mA are well understood in bacteria but its roles in animal genomes have been controversial. We show that 6mA randomly accumulates in early embryos of the cnidarianHydractinia symbiolongicarpus, with a peak at the 16-cell stage followed by clearance to background levels two cell cycles later, at the 64-cell stage – the embryonic stage at which zygotic genome activation occurs in this animal. Knocking downAlkbh1, a putative initiator of animal 6mA clearance, resulted in higher levels of 6mA at the 64-cell stage and a delay in the commencement of zygotic transcription. Our data are consistent with 6mA originating from recycled nucleotides of degraded m6A-marked maternal RNA post-fertilization. Therefore, while 6mA does not function as an epigenetic mark inHydractinia, its random incorporation into the early embryonic genome inhibits transcription. Alkbh1 functions as a genomic 6mA ‘cleaner’, facilitating timely zygotic genome activation. Given the random nature of genomic 6mA accumulation and its ability to interfere with gene expression, defects in 6mA clearance may represent a hitherto unknown cause of various pathologies.