bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of external stimulation on psychedelic state neurodynamics
Authors: Mediano Pedro A.M. , Rosas Fernando E. , Timmermann Christopher , Roseman Leor , Nutt David J. , Feilding Amanda , Kaelen Mendel , Kringelbach Morten L. , Barrett Adam B. , Seth Anil K. , Muthukumaraswamy Suresh , Bor Daniel , Carhart-Harris Robin L. 
Published: November 2020

Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes such as personality changes. These findings are particularly intriguing given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g. from wakefulness to sleep). However, little is known about how context impacts the entropy-enhancing effect of psychedelics, which carries important implications for how it can be exploited in, for example, psychedelic psychotherapy. This article investigates how brain entropy is modulated by stimulus manipulation during a psychedelic experience, by studying participants under the effects of LSD or placebo, either with gross state changes (eyes closed vs. open) or different stimulus (no stimulus vs. music vs. video). Results show that while brain entropy increases with LSD in all the experimental conditions, it exhibits largest changes when subjects have their eyes closed. Furthermore, brain entropy changes are consistently associated with subjective ratings of the psychedelic experience, but this relationship is disrupted when participants are viewing video — potentially due to a “competition” between external stimuli and endogenous LSD-induced imagery. Taken together, our findings provide strong quantitative evidence for the role of context in modulating neural dynamics during a psychedelic experience, underlining the importance of performing psychedelic psychotherapy in a suitable environment. Additionally, our findings put into question simplistic interpretations of brain entropy as a direct neural correlate of conscious level.Significance StatementThe effects of psychedelic substances on conscious experience can be substantially affected by contextual factors, which play a critical role in the outcomes of psychedelic therapy. This study shows how context can modulate not only psychological, but also neurophysiological phenomena during a psychedelic experience. Our findings reveal distinctive effects of having eyes closed after taking LSD, including a more pronounced change on the neural dynamics, and a closer correspondence between brain activity and subjective ratings. Furthermore, our results suggest a competition between external stimuli and internal psychedelic-induced imagery, which supports the practice of carrying out psychedelic therapy with patients having their eyes closed.
Rapid inactivation of SARS-CoV-2 with ozone water
Authors: Inagaki Hiroko , Saito Akatsuki , Sudaryatma Putu Eka , Sugiyama Hironobu , Okabayashi Tamaki , Fujimoto Shouichi 
Published: November 2020

AbstractAlthough ozone water is one of the promising candidates for hand hygiene to prevent fomite infection, the detailed effects of ozone water on SARS-CoV-2 have not been clarified. We evaluated the inactivating effect of ozone water against SARS-CoV-2 by its concentration and exposure time. The reduction rates of virus titer after 5 sec treatment with ozone concentrations of 1, 4, 7, and 10 mg/L were 81.4%, 93.2%, 96.6%, and 96.6%, respectively. No further decrease in virus titer was observed by the extended exposure time over 5 sec. High-concentration ozone water was considered to be effective in promptly inactivating SARS-CoV-2 virus.
IceR improves proteome coverage and data completeness in global and single-cell proteomics
Authors: Kalxdorf Mathias , Müller Torsten , Stegle Oliver , Krijgsveld Jeroen 
Published: November 2020

AbstractLabel-free proteomics by data-dependent acquisition (DDA) enables the unbiased quantification of thousands of proteins, however it notoriously suffers from high rates of missing values, thus prohibiting consistent protein quantification across large sample cohorts. To solve this, we here present IceR, an efficient and user-friendly quantification workflow that combines high identification rates of DDA with low missing value rates similar to DIA. Specifically, IceR uses ion current information in DDA data for a hybrid peptide identification propagation (PIP) approach with superior quantification precision, accuracy, reliability and data completeness compared to other quantitative workflows. We demonstrate greatly improved quantification sensitivity on published plasma and single-cell proteomics data, enhancing the number of reliably quantified proteins, improving discriminability between single-cell populations, and allowing reconstruction of a developmental trajectory. IceR will be useful to improve performance of large scale global as well as low-input proteomics applications, facilitated by its availability as an easy-to-use R-package.
A long read mapping method for highly repetitive reference sequences
Authors: Jain Chirag , Rhie Arang , Hansen Nancy , Koren Sergey , Phillippy Adam M. 
Published: November 2020

AbstractAbout 5-10% of the human genome remains inaccessible for functional analysis due to the presence of repetitive sequences such as segmental duplications and tandem repeat arrays. To enable high-quality resequencing of personal genomes, it is crucial to support end-to-end genome variant discovery using repeat-aware read mapping methods. In this study, we highlight the fact that existing long read mappers often yield incorrect alignments and variant calls within long, near-identical repeats, as they remain vulnerable toallelic bias. In the presence of a non-reference allele within a repeat, a read sampled from that region could be mapped to an incorrect repeat copy because the standard pairwise sequence alignment scoring system penalizes true variants.To address the above problem, we propose a novel, long read mapping method that addresses allelic bias by making use ofminimal confidently alignable substrings(MCASs). MCASs are formulated as minimal length substrings of a read that have unique alignments to a reference locus with sufficient mapping confidence (i.e., a mapping quality score above a user-specified threshold). This approach treats each read mapping as a collection of confident sub-alignments, which is more tolerant of structural variation and more sensitive to paralog-specific variants (PSVs) within repeats. We mathematically define MCASs and discuss an exact algorithm as well as a practical heuristic to compute them. The proposed method, referred to as Winnowmap2, is evaluated using simulated as well as real long read benchmarks using the recently completed gapless assemblies of human chromosomes X and 8 as a reference. We show that Winnowmap2 successfully addresses the issue of allelic bias, enabling more accurate downstream variant calls in repetitive sequences. As an example, using simulated PacBio HiFi reads and structural variants in chromosome 8, Winnowmap2 alignments achieved the lowest false-negative and false-positive rates (1.89%, 1.89%) for calling structural variants within near-identical repeats compared to minimap2 (39.62%, 5.88%) and NGMLR (56.60%, 36.11%) respectively.Winnowmap2 code is accessible athttps://github.com/marbl/Winnowmap
Correction of a Factor VIII genomic inversion with designer-recombinases
Authors: Lansing Felix , Mukhametzyanova Liliya , Rojo-Romanos Teresa , Iwasawa Kentaro , Kimura Masaki , Paszkowski-Rogacz Maciej , Karpinski Janet , Grass Tobias , Sonntag Jan , Schneider Paul Martin , Günes Ceren , Hoersten Jenna , Schmitt Lukas Theo , Rodriguez-Muela Natalia , Knöfler Ralf , Takebe Takanori , Buchholz Frank 
Published: November 2020

AbstractDespite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct a 140 kb genomic inversion of the F8 gene, which is frequently found in patients diagnosed with severe Hemophilia A. Employing substrate-linked directed molecular evolution, we developed a fused heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells. Transient RecF8 treatment of endothelial cells, differentiated from patient derived induced pluripotent stem cells (iPSCs) of a hemophilic donor, resulted in prominent correction of the inversion and restored Factor VIII mRNA expression. Our data suggests that designer-recombinases may represent efficient and specific means towards treatment of monogenic diseases caused by large gene inversions.
Downstream of gasdermin D cleavage, a Ragulator-Rag-mTORC1 pathway promotes pore formation and pyroptosis
Authors: Evavold Charles L. , Hafner-Bratkovič Iva , Kagan Jonathan C. 
Published: November 2020

AbstractThe process of pyroptosis is mediated by inflammasomes and a downstream effector known as gasdermin D (GSDMD). Upon cleavage by inflammasome-associated caspases, the N-terminal domain of GSDMD forms membrane pores that promote cytolysis. Numerous proteins are recognized to promote GSDMD cleavage, but none are known to be required for pore formation after GSDMD cleavage. Herein, we report a forward genetic screen that was designed to identify regulators of pyroptosis that act downstream of GSDMD cleavage. This screen identified several components of the Ragulator-Rag complex, which is known for its metabolic control of mTOR. Mechanistic studies revealed that Ragulator-Rag is not necessary for GSDMD localization to the plasma membrane, but is necessary for pore formation and mitochondrial inactivation. Downstream of Ragulator-Rag is mTORC1, which we found to promote pyroptosis in response to diverse natural stimuli, including infection. GSDMD therefore requires a Ragulator-Rag-mTORC1 pathway in order to form pores and execute pyroptosis.
Microbiota functional activity biosensors for characterizing nutrient utilizationin vivo
Authors: Wesener Darryl A. , Beller Zachary W. , Peters Samantha L. , Rajabi Amir , Dimartino Gianluca , Giannone Richard J. , Hettich Robert L. , Gordon Jeffrey I. 
Published: November 2020

AbstractMethods for measuring gut microbiota biochemical activitiesin vivoare needed to characterize its functional states in health and disease. To illustrate one approach, an arabinan-containing polysaccharide was purified from pea fiber, its structure defined, and forward genetic and proteomic analyses used to compare its effects, versus unfractionated pea fiber and sugar beet arabinan, on a human gut bacterial strain consortium in gnotobiotic mice. We produced ‘Microbiota Functional Activity Biosensors’ (MFABs) consisting of glycans covalently-linked to the surface of fluorescent paramagnetic microscopic glass beads. Three MFABs, each containing a unique glycan/fluorophore combination, were simultaneously orally gavaged into gnotobiotic mice, recovered from their intestines, and analyzed to directly quantify bacterial metabolism of structurally distinct arabinans in different human diet contexts. Colocalizing pea-fiber arabinan and another polysaccharide (glucomannan) on the bead surface enhancedin vivometabolism of glucomannan. MFABs represent a potentially versatile platform for developing new prebiotics and more nutritious foods.
Adipose Triglyceride Lipase is needed for homeostatic control of Sterol Element-Binding Protein-1c driven hepatic lipogenesis
Authors: Wieser Beatrix Irene , de la Sancha Paola Peña , Schauer Silvia , Reicher Helga , Sattler Wolfgang , Breinbauer Rolf , Schweiger Martina , Espenshade Peter John , Zechner Rudolf , Hoefler Gerald , Vesely Paul Willibald 
Published: November 2020

AbstractSterol Regulatory Element-Binding Protein-1c (SREBP-1c) is translated as an inactive precursor-protein that is proteolytically activated to promote fatty-acid (FA) biosynthesis, when unsaturated (u)FAs are scarce. During fasting, however, lipogenesis is low, and adipose-tissue lipolysis supplies the organism with FAs. Adipose TriGlyceride Lipase (ATGL) is the rate-limiting enzyme for lipolysis, and it preferentially hydrolyzes uFAs. Therefore, we hypothesized that ATGL-derived FAs may suppress the proteolytic activation of SREBP-1c in the liver. Here we show that (i) SREBP-1c is inactive during fasting but active after refeeding, (ii) uFA species liberated by ATGL suppress SREBP-1c activationin vitro, (iii) SREBP-1c is hyper-activated in livers of mice lacking ATGL, and (iv) pharmacological inhibition of ATGL selectively activates SREBP-1c in hepatocytes. Our findings highlight an ATGL/SREBP-1c axis, instrumental to coordinate lipogenesis and lipolysis, whose homeostatic regulation is crucial to avoid severe diseases including diabetes, cardiomyopathy, and even cancer.
The SARS-CoV-2 RNA interactome
Authors: Lee Sungyul , Lee Young-suk , Choi Yeon , Son Ahyeon , Park Youngran , Lee Kyung-Min , Kim Jeesoo , Kim Jong-Seo , Kim V. Narry 
Published: November 2020

AbstractSARS-CoV-2 is an RNA virus whose success as a pathogen relies on its ability to repurpose host RNA-binding proteins (RBPs) to form its own RNA interactome. Here, we developed and applied a robust ribonucleoprotein capture protocol to uncover the SARS-CoV-2 RNA interactome. We report 109 host factors that directly bind to SARS-CoV-2 RNAs including general antiviral factors such as ZC3HAV1, TRIM25, and PARP12. Applying RNP capture on another coronavirus HCoV-OC43 revealed evolutionarily conserved interactions between viral RNAs and host proteins. Network and transcriptome analyses delineated antiviral RBPs stimulated by JAK-STAT signaling and proviral RBPs responsible for hijacking multiple steps of the mRNA life cycle. By knockdown experiments, we further found that these viral-RNA-interacting RBPs act against or in favor of SARS-CoV-2. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.
Whole genome genetic variation and linkage disequilibrium in a diverse collection ofListeria monocytogenesisolates
Authors: Louha Swarnali , Meinersmann Richard J. , Glenn Travis C. 
Published: November 2020

AbstractWe performed whole-genome multi-locus sequence typing for 2554 genes in a large and heterogenous panel of 180Listeria monocytogenesstrains having diverse geographical and temporal origins. The subtyping data was used for characterizing genetic variation and evaluating patterns of linkage disequilibrium in the pan-genome ofL. monocytogenes. Our analysis revealed the presence of strong linkage disequilibrium inL. monocytogenes, with ∼99% of genes showing significant non-random associations with a large majority of other genes in the genome. Twenty-seven loci having lower levels of association with other genes were considered to be potential “hot spots” for horizontal gene transfer (i.e., recombination via conjugation, transduction, and/or transformation). The patterns of linkage disequilibrium inL. monocytogenessuggest limited exchange of foreign genetic material in the genome and can be used as a tool for identifying new recombinant strains. This can help understand processes contributing to the diversification and evolution of this pathogenic bacteria, thereby facilitating development of effective control measures.
Reducedech-6Expression Attenuates Fat-induced Premature Aging inC. elegans
Authors: Liu Yasmine J. , Gao Arwen W. , Smith Reuben L. , Janssens Georges E. , Panneman Daan M. , Jongejan Aldo , van Weeghel Michel , Vaz Frédéric M. , Silvestrini Melissa J. , Lapierre Louis R. , MacInnes Alyson W. , Houtkooper Riekelt H. 
Published: November 2020

SUMMARYDeregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the geneech-6encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan inCaenorhabditis elegans, while a basal expression ofech-6was important for survival under normal dietary conditions. Lipidomics revealed that supplementation of fat inech-6-silenced worms had marginal effects on lipid profiles, suggesting an alternative fat utilization for energy production. Transcriptomics further suggest a causal relation between the lysosomal pathway, energy production, and the longevity effect conferred by the interaction betweenech-6and high-fat diets. Indeed, enhancing energy production from endogenous fat by overexpressing lysosomal lipaselipl-4recapitulated the lifespan effects of high-fat diets onech-6-silenced worms. Collectively, these results reveal that the geneech-6modulates metabolic flexibility and may be a target for promoting metabolic health and longevity.
Neutrophils encompass a regulatory subset suppressing T cells in apparently healthy cattle and mice
Authors: Rambault Marion , Doz-Deblauwe Émilie , Vern Yves Le , Carreras Florence , Cunha Patricia , Germon Pierre , Rainard Pascal , Winter Nathalie , Remot Aude 
Published: November 2020

ABSTRACTNeutrophils that reside in the bone marrow are switly recruited from circulating blood to fight infections. For a long time, these first line defenders were considered as microbe killers. However their role is far more complex as cross talk with T cells or dendritic cells have been described for human or mouse neutrophils. In cattle, these new roles are not documented yet. We identified a new subset of regulatory neutrophils that is present in the mouse bone marrow or circulate in cattle blood under steady state conditions. These regulatory neutrophils that display MHC-II on the surface are morphologically indistinguishable from classical MHC-IInegneutrophils. However MHC-IIposand MHC-IInegneutrophils display distinct transcriptomic profiles. While MHC-IInegand MHC-IIposneutrophils display similar bacterial phagocytosis or killing activity, MHC-IIposonly are able to suppress T cell proliferation under contact-dependent mechanisms. Regulatory neutrophils are highly enriched in lymphoid organs as compared to their MHC-IInegcounterparts and in the mouse they express PDL-1, an immune checkpoint involved in T-cell blockade. Our results emphasize neutrophils as true partners of the adaptive immune response, including in domestic species. They open the way for discovery of new biomarkers and therapeutic interventions to better control cattle diseases.
Common transcriptional programme of liver fibrosis in mouse genetic models and humans
Authors: Cokan Kaja Blagotinšek , Urlep Žiga , Moškon Miha , Mraz Miha , Kong Xiang Y. , Eskild Winnie , Rozman Damjana , Juvan Peter , Režen Tadeja 
Published: November 2020

AbstractMultifactorial metabolic diseases, such as non-alcoholic fatty liver disease, are a major burden of modern societies and frequently present with no clearly defined molecular biomarkers. Herein we used systems medicine approaches to decipher signatures of liver fibrosis in mouse models with malfunction in genes from unrelated biological pathways. Enrichment analyses of KEGG, Reactome and TRANSFAC databases complemented with genome-scale metabolic modelling revealed fibrotic signatures highly similar to liver pathologies in humans. The diverse genetic models of liver fibrosis exposed a common transcriptional programme with activated ERα signalling, and a network of interactions between regulators of lipid metabolism and transcription factors from cancer pathways and immune system. The novel hallmarks of fibrosis are downregulated lipid pathways, including fatty acid, bile acid, and steroid hormone metabolism. Moreover, distinct metabolic subtypes of liver fibrosis were proposed, supported by unique enrichment of transcription factors based on the type of insult, disease stage, or sex.
Structural and functional plasticity in the dorsolateral geniculate nucleus of mice following bilateral enucleation
Authors: Bhandari Ashish , Ward Thomas W. , Smith Jennie , Van Hook Matthew J. 
Published: November 2020

AbstractWithin the nervous system, plasticity mechanisms attempt to stabilize network activity following disruption by injury, disease, or degeneration. Optic nerve injury and age-related diseases can induce homeostatic-like responses in adulthood. We tested this possibility in the thalamocortical (TC) neurons in the dorsolateral geniculate nucleus (dLGN) using patch-clamp electrophysiology, optogenetics, immunostaining, and single-cell dendritic analysis following loss of visual input via bilateral enucleation. We observed progressive loss of vGlut2-positive retinal terminals in the dLGN indicating degeneration post-enucleation that was coincident with changes in microglial morphology indicative of microglial activation. Consistent with the decline of vGlut2 puncta, we also observed loss of retinogeniculate (RG) synaptic function assessed using optogenetic activation of RG axons while performing whole-cell voltage clamp recordings from TC neurons in brain slices. Surprisingly, we did not detect any significant changes in the frequency of miniature post-synaptic currents (mEPSCs) or corticothalamic feedback synapses. Analysis of TC neuron dendritic structure from single-cell dye fills revealed a gradual loss of dendrites proximal to the soma, where TC neurons receive the bulk of RG inputs. Finally, analysis of action potential firing demonstrated that TC neurons have increased excitability following enucleation, firing more action potentials in response to depolarizing current injections. Our findings show that degeneration of the retinal axons/optic nerve and loss of RG synaptic inputs induces structural and functional changes in TC neurons, consistent with neuronal attempts at compensatory plasticity in the dLGN.
scCapsNet-mask: an automatic version of scCapsNet
Authors: Wang Lifei , Zhang Jiang , Cai Jun 
Published: November 2020

AbstractSummaryRecently we developed scCapsNet, an interpretable deep learning cell type classifier for single cell RNA sequencing data, based on capsule network. However, the running process of scCapsNet is not fully automatic, in which a manual intervention is required for getting the final results. Here we present scCapsNet-mask, an updated version of scCapsNet that utilizes a mask to fully automate the running process of scCapsNet. scCapsNet-mask could constrain the internal parameter coupling coefficients and result in a one to one correspondence between the primary capsule and type capsule. Based on those bijective mapping between primary capsule and type capsule, the model could automatically extract the cell type related genes according to weight matrix connecting input and primary capsule, without a need for manual inspection of the relationship between primary capsules and type capsules. The scCapsNet-mask is evaluated on two single cell RNA sequence datasets. The results show that scCapsNet-mask not only retains the merits of the original scCapsNet with high classification accuracy and high interpretability, but also has the virtue of automatic processing.