bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feedback information sharing in the human brain reflects bistable perception in the absence of report
Authors: Canales-Johnson Andres , Beerendonk Lola , Chennu Srivas , Davidson Matthew J. , Ince Robin A.A. , van Gaal Simon 
Published: November 2021

AbstractIn the search for the neural basis of conscious experience, perception and the cognitive processes associated with reporting perception are typically confounded as neural activity is recorded while participants explicitly report what they experience. Here we present a novel way to disentangle perception from report using eye-movement analysis techniques based on convolutional neural networks and neurodynamical analyses based on information theory. We use a bistable visual stimulus that instantiates two well-known properties of conscious perception: integration and differentiation. At any given moment, observers either perceive the stimulus as one integrated unitary object or as two differentiated objects that are clearly distinct from each other. Using electroen-cephalography, we show that measures of integration and differentiation based on information theory closely follow participants’ perceptual experience of those contents when switches were reported. We observed increased information integration between anterior to posterior electrodes (front to back) prior to a switch to the integrated percept, and higher information differentiation of anterior signals leading up to reporting the differentiated percept. Crucially, information integration was closely linked to perception and even observed in a no-report condition when perceptual transitions were inferred from eye movements alone. In contrast, the link between neural differentiation and perception was observed solely in the active report condition. Our results, therefore, suggest that perception and the processes associated with report require distinct amounts of anterior-posterior network communication and anterior information differentiation. While front-to-back directed information is associated with changes in the content of perception when viewing bistable visual stimuli, regardless of report, frontal information differentiation was absent in the no-report condition and therefore is not directly linked to perceptionper se.
Estimated limits of organism-specific training for epitope prediction
Authors: Ashford Jodie , Campelo Felipe 
Published: November 2021

AbstractBackgroundThe identification of linear B-cell epitopes remains an important task in the development of vaccines, therapeutic antibodies and several diagnostic tests. Machine learning predictors are trained to flag potential epitope candidates for experimental validation and currently, most predictors are trained as generalist models using large, heterogeneous data sets. Recently, organism-specific training has been shown to improve prediction performance for data-rich organisms. Unfortunately, for most organisms, large volumes of validated epitope data are not yet available. This article investigates the limits of organism-specific training for epitope prediction. It explores the validity of organism-specific training for data-poor organisms by examining how the size of the training data set affects prediction performance. It also compares the performance of organism-specific training under simulated data-poor conditions to that of models trained using traditional large heterogeneous and hybrid data sets.ResultsThis work shows how models trained on small organism-specific data sets can outperform similar models trained on (potentially much larger) heterogeneous and mixed data sets. The results reported indicate that as few as 20 labelled peptides from a given pathogen can be sufficient to generate models that outperform widely-used predictors from the literature, which are trained on heterogeneous data. Models trained using more than about 100 to 150 organism-specific peptides perform consistently better than most generalist models across a wide variety of performance measures, and in some cases can even approach the performance of organism-specific models trained on considerably larger data sets.ConclusionsOrganism-specific training improves linear B-cell epitope prediction performance even in situations when only small training sets are available, which opens new possibilities for the development of bespoke, high-performance predictive models when studying data-poor organisms such as emerging or neglected pathogens.
Dopamine mediates the bidirectional update of interval timing
Authors: Jakob Anthony M.V. , Mikhael John G. , Hamilos Allison E. , Assad John A. , Gershman Samuel J. 
Published: November 2021

AbstractThe role of dopamine as a reward prediction error signal in reinforcement learning tasks has been well-established over the past decades. Recent work has shown that the reward prediction error interpretation can also account for the effects of dopamine on interval timing by controlling the speed of subjective time. According to this theory, the timing of the dopamine signal relative to reward delivery dictates whether subjective time speeds up or slows down: Early DA signals speed up subjective time and late signals slow it down. To test this bidirectional prediction, we reanalyzed measurements of dopaminergic neurons in the substantia nigra pars compacta of mice performing a self-timed movement task. Using the slope of ramping dopamine activity as a read-out of subjective time speed, we found that trial-by-trial changes in the slope could be predicted from the timing of dopamine activity on the previous trial. This result provides a key piece of evidence supporting a unified computational theory of reinforcement learning and interval timing.
Single molecule tracking of bacterial cell surface cytochromes reveals dynamics that impact long-distance electron transport
Authors: Chong Grace W. , Pirbadian Sahand , Zhao Yunke , Zacharoff Lori A. , Pinaud Fabien , El-Naggar Mohamed Y. 
Published: November 2021

AbstractUsing a series of multiheme cytochromes, the metal-reducing bacteriumShewanella oneidensisMR-1 can perform extracellular electron transfer (EET) to respire redox-active surfaces, including minerals and electrodes outside the cell. While the role of multiheme cytochromes in transporting electrons across the cell wall is well established, these cytochromes were also recently found to facilitate long-distance (micrometer-scale) redox conduction along outer membranes and across multiple cells bridging electrodes. Recent studies proposed that long-distance conduction arises from the interplay of electron hopping and cytochrome diffusion, which allows collisions and electron exchange between cytochromes along membranes. However, the diffusive dynamics of the multiheme cytochromes have never been observed or quantifiedin vivo, making it difficult to assess their hypothesized contribution to the collision-exchange mechanism. Here we use quantum dot labeling, total internal reflection fluorescence microscopy, and single-particle tracking to quantify the lateral diffusive dynamics of the outer membrane-associated decaheme cytochromes MtrC and OmcA, two key components of EET inS. oneidensis. We observe confined diffusion behavior for both quantum dot-labeled MtrC and OmcA along cell surfaces (diffusion coefficientsDMtrC= 0.0192 ± 0.0018 μm2/s,DOmcA= 0.0125 ± 0.0024 μm2/s) and the membrane extensions thought to function as bacterial nanowires. We find that these dynamics can trace a path for electron transport via overlap of cytochrome trajectories, consistent with the long-distance conduction mechanism. The measured dynamics inform kinetic Monte Carlo simulations that combine direct electron hopping and redox molecule diffusion, revealing significant electron transport rates along cells and membrane nanowires.SignificanceMultiheme cytochromes inShewanella oneidensisMR-1 transport electrons across the cell wall, in a process called extracellular electron transfer. These electron conduits can also enable electron transport along and between cells. While the underlying mechanism is thought to involve a combination of electron hopping and lateral diffusion of cytochromes along membranes, these diffusive dynamics have never been observedin vivo. Here, we observe the mobility of quantum dot-labeled cytochromes on living cell surfaces and membrane nanowires, quantify their diffusion with single-particle tracking techniques, and simulate the contribution of these dynamics to electron transport. This work reveals the impact of redox molecule dynamics on bacterial electron transport, with implications for understanding and harnessing this process in the environment and bioelectronics.
Biological Factors and Self-Perception of Stress Predict Human Freeze-Like Responses in the Context of Self-Defence Training and Personal Experience with Violence
Authors: Lenart Peter , Vít Michal , Marečková Klára , Novák Jan , Zlámal Filip , Mikl Michal , Reguli Zdenko , Bugala Martin , Čihounková Jitka , Přecechtěl Pavel , Malčík Vojtěch , Vojtíšek Tomáš , Kučera Jan , Kučerová Jana Fialová , Hajnová Veronika , Tomandlová Marie , Šíp Radek , Ráčková Lucie , Grulichová Markéta , Tomandl Josef , Brázdil Milan , Bienertova-Vasku Julie 
Published: November 2021

AbstractMany animals react to threatening stimuli such as a predator attacks by freezing. However, little experimental research investigated freeze response in humans. Here, we have employed practices commonly used in self-defence training to create two unique scenarios simulating armed physical attacks. Sixty healthy men volunteers divided into three groups of twenty (untrained, trained but unexperienced, trained and experienced) underwent these scenarios accompanied by measurement of biochemical, physiological, and psychological markers of stress. All participants also underwent an fMRI session during which they observed neutral and negative images from the International Affective Picture System (IAPS). Our results show that scenarios simulating physical attacks can induce a freeze-like response in men. In addition, we demonstrate that while electrodermal activity (EDA), subjective stress perception, and brain activity in fMRI predict freeze-like response in men, their effect on freeze-like response is entirely dependent on the level of training and experience of a given individual.
Demographic history shapes genomic variation in an intracellular parasite with a wide geographic distribution
Authors: Angst Pascal , Ebert Dieter , Fields Peter D. 
Published: November 2021

AbstractAnalyzing variation in a species’ genomic diversity can provide insights into its historical demography, biogeography and population structure, and thus, its ecology and evolution. Although such studies are rarely undertaken for parasites, they can be highly revealing because of the parasite’s coevolutionary relationships with hosts. Modes of reproduction and transmission are thought to be strong determinants of genomic diversity for parasites and vary widely among microsporidia (fungal-related intracellular parasites), which are known to have high intraspecific genetic diversity and interspecific variation in genome architecture. Here we explore genomic variation in the microsporidium Hamiltosporidium, a parasite of the freshwater crustacean Daphnia magna, looking especially at which factors contribute to nucleotide variation. Genomic samples from 18 Eurasian populations and a new, long-read based reference genome were used to determine the roles that reproduction mode, transmission mode and geography play in determining population structure and demographic history. We demonstrate two main H. tvaerminnensis lineages and a pattern of isolation-by-distance, but note an absence of congruence between these two parasite lineages and the two Eurasian host lineages. We suggest a comparatively recent parasite spread through Northern Eurasian host populations after a change from vertical to mixed-mode transmission and the loss of sexual reproduction. While gaining knowledge about the ecology and evolution of this focal parasite, we also identify common features that shape variation in genomic diversity for many parasites, e.g., distinct modes of reproduction and the intertwining of host–parasite demographies.
Retinal OFF ganglion cells allow detection of quantal shadows at starlight
Authors: Westö Johan , Martyniuk Nataliia , Koskela Sanna , Turunen Tuomas , Pentikäinen Santtu , Ala-Laurila Petri 
Published: November 2021

SUMMARYPerception of light in darkness requires no more than a handful of photons and this remarkable behavioral performance can be directly linked to a particular retinal circuit – the retinal ON pathway. However, the neural limits to shadow detection in very dim light have remained unresolved. Here, we unravel the neural mechanisms that determine the sensitivity of mice to the dimmest light decrements by measuring signals from the most sensitive ON and OFF retinal ganglion cell types and by correlating their signals with visually guided behavior. We show that mice can detect shadows when only a few photon absorptions are missing among thousands of rods. Behavioral detection of “quantal” shadows relies only on the retinal OFF pathway and is limited by noise and losses of single-photon signals in retinal processing. Thus, in the dim-light regime, light increments and decrements are encoded separately via the ON and OFF retinal pathways, respectively.
MS2Rescore: Data-driven rescoring dramatically boosts immunopeptide identification rates
Authors: Declercq Arthur , Bouwmeester Robbin , Hirschler Aurélie , Carapito Christine , Degroeve Sven , Martens Lennart , Gabriels Ralf 
Published: November 2021

AbstractImmunopeptidomics aims to identify Major Histocompatibility Complex-presented peptides on every cell that can be used in anti-cancer vaccine development. However, existing immunopeptidomics data analysis pipelines suffer from the non-tryptic nature of immunopeptides, complicating their identification. Previously, peak intensity predictions by MS2PIP and retention time predictions by DeepLC, have been shown to improve tryptic peptide identifications when rescoring peptide-spectrum matches with Percolator. However, as MS2PIP was tailored towards tryptic peptides, we have here retrained MS2PIP to include non-tryptic peptides. Interestingly, the new models not only greatly improve predictions for immunopeptides, but also yield further improvements for tryptic peptides. We show that the integration of new MS2PIP models, DeepLC, and Percolator in one software package, MS2Rescore, increases spectrum identification rate and unique identified peptides with 46% and 36% compared to standard Percolator rescoring at 1% FDR. Moreover, MS2Rescore also outperforms the current state-of-the-art in immunopeptide-specific identification approaches. Integration of immunopeptide MS2PIP models, DeepLC, and Percolator into MS2Rescore thus allows substantial improved identification of novel epitopes from existing immunopeptidomics workflows.
Empirical Bayes functional models for hydrogen deuterium exchange mass spectrometry
Authors: Crook Oliver M. , Chung Chun-wa , Deane Charlotte M. 
Published: November 2021

AbstractA protein’s structure is state-specific and a key determinant of its function. Proteins can undergo subtle structural changes when binding to another protein, small molecule or as a result of environmental perturbations. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a technique to explore differential protein structure by examining the rate of deuterium incorporation for specific peptides. This rate will be altered upon structural perturbation and detecting significant changes to this rate requires a statistical test. To determine rates of incorporation, HDX-MS measurements are frequently made over a time course. However, current statistical testing procedures ignore the correlations in the temporal dimension of the data. Using tools from functional data analysis, we develop a testing procedure that explicitly incorporates a physical model of hydrogen deuterium exchange. To further improve statistical power, we develop an empirical Bayes version of our method, allowing us to borrow information across peptides and stabilise variance estimates for low sample sizes. Our approach has increased power, reduces false positives and improves interpretation over linear model-based approaches. Due to the improved flexibility of our method, we can apply it to a multi-antibody epitope-mapping experiment where current approaches are inapplicable due insufficient flexibility. Hence, our approach allows HDX-MS to be applied in more experimental scenarios and reduces the burden on experimentalists to produce excessive replicates. Our approach is implemented in the R-package “hdxstats”: https://github.com/ococrook/hdxstats.
LRH-1/NR5A2 regulates the PTGS2-PGE2-PTGER1 signalling axis contributing to islet survival and antidiabetic actions of the agonist BL001
Authors: Vázquez Eugenia Martin , Cobo-Vuilleumier Nadia , Legido Raquel Araujo , Nola Emanuele , Bermudo Lucia López , Crespo Alejandra , Romero-Zerbo Silvana Y. , García-Fernández Maria , Montalvo Alejandro Martin , Rojas Anabel , Comaills Valentine , Bérmudez-Silva Francisco J. , Gannon Maureen , Martin Franz , Lorenzo Petra I. , Gauthier Benoit R. 
Published: November 2021

ABSTRACTWe have previously described a role of LRH-1/NR5A2 in islet morphogenesis during postnatal development and reported that the treatment with BL001, an agonist of LRH-1/NR5A2, protects islets against-stress induced apoptosis and reverts hyperglycemia in 3 mouse models of Type 1 Diabetes Mellitus (T1DM). Islet transcriptome profiling revealed that most differentially expressed genes after BL001 treatment are involved in immunomodulation, among them, the increase in PTGS2/COX2 expression. Herein, we dissected the cellular and molecular branches of the BL001/LRH-1/NR5A2 signalling axis in order to chart the mode of action confering beta cell protection and hyperglycaemia reversion. We found that constitutive LRH-1/NR5A2 ablation within the insulin expression domain (RIP-Cre mouse model) caused a significant beta cell mass reduction characterized by blunted proliferation correlating with animal growth retardation, weight loss and hypoglycemia, leading to lethality before weaning. Using an inducible approach (pdx1PBCreER™ mouse model), specific deletion of LRH-1/NR5A2 in adult beta cells abolished the anti diabetic effect of BL001 in streptozotocin treated mice, correlating with complete beta-cell mass destruction. Additionally, BL001 induced Ptgs2 expression, was blunted in islets lacking LRH-1/NR5A2. The combined BL001/cytokine treatment did not further stimulate Ptgs2 expression above levels detected with cytokine alone yet secreted PGE2 levels were increased 5-fold. Inactivation of PTGS2 blunted induction of the target and its product PGE2 in islets treated with cytokines alone or with BL001. Importantly, PTGS2 inactivated islets were refractory to the BL001 protective effect under cytokine attack as evidenced by increased Bax expression levels, cytochrome C release and cleaved PARP. The PTGER1 antagonist ONO-8130, but not the PTGER4 antagonist L-161,982, negated BL001-mediated islet survival. Our results establish that the beneficial properties of BL001 against stress-induced cell death are specifically conveyed by LRH-1/NR5A2 activation in beta cells and downstream stimulation of the PTGS2-PGE2/PTGER1 signalling axis.
Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies
Authors: Leonard Alexander S. , Crysnanto Danang , Fang Zih-Hua , Heaton Michael P , Vander Ley Brian L. , Herrera Carolina , Bollwein Heinrich , Bickhart Derek M. , Kuhn Kristen L. , Smith Timothy PL. , Rosen Benjamin D. , Pausch Hubert 
Published: November 2021

AbstractAdvantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. We generated haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the currentBos taurusreference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT was sufficient to produce two haplotype-resolved assemblies meeting the standards set by the Vertebrate Genome Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrated significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identified 90 thousand structural variants including 931 overlapping with coding sequences; this approach revealed variants affectingQRICH2, PRDM9, HSPA1A, TAS2R46, andGCthat have potential to affect phenotype.
Bacterial colonisation dynamics of household plastics in a coastal environment
Authors: Lear Luke , Padfield Daniel , Dowsett Tirion , Jones Maia , Kay Suzanne , Hayward Alex , Vos Michiel 
Published: November 2021

AbstractAccumulation of plastics in the marine environment has widespread detrimental consequences for ecosystems and wildlife. Marine plastics are rapidly colonised by a wide diversity of bacteria, including human pathogens, posing potential risks to human health. Here, we investigate the effect of polymer type, residence time and estuarine location on bacterial colonisation of common household plastics, including pathogenic bacteria. To do so, we submerged five main household plastic types: low-density PE (LDPE), high-density PE (HDPE), polypropylene (PP), polyvinyl chloride (PVC) and polyethylene terephthalate (PET) at an estuarine site in Cornwall (U.K.) and tracked bacterial colonisation dynamics. Using both culture-dependent and culture-independent approaches, we found that bacteria rapidly colonised plastics irrespective of polymer type. While biofilm community composition changed with colonisation time, no difference was observed between polymer types. Likewise, the presence of pathogenic bacteria, quantified using the insect modelGalleria mellonella, increased over a five-week period, with no consistent differences observed between polymer types. Pathogens isolated from plastic biofilms usingGalleriaenrichment includedSerratiaandEnterococcusspecies and harboured a wide range of antimicrobial resistance genes. Our findings show that plastics in coastal waters are rapidly colonised by a wide diversity of bacteria, including known human pathogens, independent of polymer type.