bluuebunny/crossref_metadata_2025_split huggingface dataset:
The monologue of the double: allocentric reduplication of the own voice alters bodily self perception
Authors: Lesur Marte Roel , Bolt Elena , Lenggenhager Bigna 
Published: August 2020

AbstractDuring autoscopic phenomena, people perceive a double of themselves in extrapersonal space. Such clinical allocentric self-experiences often co-occur with auditory hallucinations, yet experimental setups to induce similar illusions in healthy participants have been limited to visual doubles. We investigated whether feeling the presence of an auditory double could be provoked in healthy participants and how it might affect spatial aspects of bodily self-consciousness. We recorded the own versus another person’s voice while walking around in the room using binaural headphones from an egocentric and an allocentric perspective. In comparison to listening to their own moving voice egocentrically, when listening to themselves allocentrically, participants reported a strong feeling of a presence with a similarly high degree of self-identification, suggesting a successful induction of the feeling of an acoustic doppelganger. When pointing to the source of the own voice participants localized it closer to themselves than when listening to another person’s voice, suggesting a change in spatial perception. Interestingly, the opposite pattern was found in participants that had previous hallucinatory experiences. These findings show that listening to one’s own voice allocentrically can manipulate bodily self-consciousness and self-related spatial perception. This paradigm enables the experimental study of the relationship between auditory vocal hallucinations and bodily self-consciousness, bridging important clinical phenomena and experimental knowledge.
Starburst amacrine cells amplify optogenetic visual restoration through gap junctions
Authors: Katada Yusaku , Kunimi Hiromitsu , Serizawa Naho , Lee Deokho , Kobayashi Kenta , Negishi Kazuno , Okano Hideyuki , Tanaka Kenji F. , Tsubota Kazuo , Kurihara Toshihide 
Published: August 2020

AbstractEctopic induction of optogenetic actuators, such as channelrhodopsin, is a promising approach to restoring vision in the degenerating retina. However, the cell type-specific response of ectopic photoreception has not been well understood. It is limited to obtain efficient gene expression in a specifically targeted cell population by a transgenic approach. In the present study, we established a murine model with high efficiency of gene induction to retinal ganglion cells (RGCs)- and amacrine cells using an improved tetracycline transactivator-operator bipartite system (KENGE-tet system). To investigate the cell type-specific visual restorative effect, we expressed the channelrhodopsin gene into RGCs and amacrine cells using the KENGE-tet system. As a result, enhancement in the visual restorative effect was observed to RGCs and starburst amacrine cells. In conclusion, a photoresponse from amacrine cells may enhance the maintained response of RGCs and further increase/improve the visual restorative effect.
Four newScopalinafrom Southern California: the first Scopalinida (Porifera: Demospongiae) from the temperate Eastern Pacific
Authors: Turner Thomas L. 
Published: August 2020

AbstractSponges (phylum Porifera) are common inhabitants of kelp forest ecosystems in California, but their diversity and ecological importance are poorly characterized in this biome. Here I use freshly collected samples to describe the diversity of the order Scopalinida in California. Though previously unknown in the region, four new species are described here:Scopalina nausicaesp. nov.,S. kuyamusp. nov.,S. goletensissp. nov., andS. jalisp. nov.. These discoveries illustrate the considerable uncharacterized sponge diversity remaining in California kelp forests, and the utility of SCUBA-based collection to improve our understanding of this diversity.
Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions
Authors: Kim Jong Hyuk , Megquier Kate , Thomas Rachael , Sarver Aaron L. , Song Jung Min , Kim Yoon Tae , Cheng Nuojin , Schulte Ashley J. , Linden Michael A. , Murugan Paari , Oseth LeAnn , Forster Colleen L. , Elvers Ingegerd , Swofford Ross , Turner-Maier Jason , Karlsson Elinor K. , Breen Matthew , Lindblad-Toh Kerstin , Modiano Jaime F. 
Published: August 2020

AbstractSporadic angiosarcomas (ASs) are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types of cancers, but their existence and significance remain unclear in sporadic ASs. In this study, we leveraged RNA sequencing data from thirteen human ASs and 76 spontaneous canine hemangiosarcomas (HSAs) to identify fusion genes associated with spontaneous vascular malignancies. Ten novel protein-coding fusion genes, includingTEX2-PECAM1andATP8A2-FLT1,were identified in seven of the thirteen human tumors, with two tumors showing mutations ofTP53. HRASandNRASmutations were found in ASs without fusions orTP53mutations. We found fifteen novel protein-coding fusion genes includingMYO16-PTK2, GABRA3-FLT1,andAKT3-XPNPEP1in eleven of the 76 canine HSAs; these fusion genes were seen exclusively in tumors of the angiogenic molecular subtype that contained recurrent mutations inTP53, PIK3CA, PIK3R1,andNRAS.In particular, fusion genes and mutations ofTP53co-occurred in tumors with higher frequency than expected by random chance, and they enriched gene signatures predicting activation of angiogenic pathways. Comparative transcriptomic analysis of human ASs and canine HSAs identified shared molecular signatures associated with activation of PI3K/AKT/mTOR pathways. Our data show that, while driver events of malignant vasoformative tumors of humans and dogs include diverse mutations and stochastic rearrangements that create novel fusion genes, convergent transcriptional programs govern the highly conserved morphological organization and biological behavior of these tumors in both species.
Efficacy of Targeting SARS-CoV-2 by CAR-NK Cells
Authors: Ma Minh , Badeti Saiaditya , Geng Ke , Liu Dongfang 
Published: August 2020

ABSTRACTSARS-CoV-2, which causes COVID-19 disease, is one of greatest global pandemics in history. No effective treatment is currently available for severe COVID-19 disease. One strategy for implementing cell-based immunity involves the use of chimeric antigen receptor (CAR) technology. Unlike CAR T cells, which need to be developed using primary T cells derived from COVID-19 patients with lymphopenia, clinical success of CAR NK cell immunotherapy is possible through the development of allogeneic, universal, and ‘off-the-shelf’ CAR-NK cells from a third party, which will significantly broaden the application and reduce costs. Here, we develop a novel approach for the generation of CAR-NK cells for targeting SARS-CoV-2. CAR-NK cells were generated using the scFv domain of CR3022 (henceforth, CR3022-CAR-NK), a broadly neutralizing antibody for SARS-CoV-1 and SARS-CoV-2. CR3022-CAR-NK cells can specifically bind to RBD of SARS-CoV-2 and pseudotyped SARS-CoV-2 S protein, and can be activated by pseudotyped SARS-CoV-2-S viral particlesin vitro.Further, CR3022-CAR-NK cells can specifically kill pseudo-SARS-CoV-2 infected target cells. Thus, ‘off-the-shelf’ CR3022-CAR-NK cells may have the potential to treat patients with severe COVID-19 disease.
Assessment of ethanol-induced toxicity on iPSC-derived human dopaminergic neurons using a novel high-throughput mitochondrial neuronal health (MNH) assay
Authors: Zink Annika , Conrad Josefin , Telugu Narasimha Swami , Diecke Sebastian , Heinz Andreas , Wanker Erich , Priller Josef , Prigione Alessandro 
Published: August 2020

AbstractExcessive ethanol exposure can cause mitochondrial and cellular toxicity. In order to discover potential counteracting interventions, it is essential to develop assays capable of capturing the consequences of ethanol exposure in human dopaminergic (DA) neurons, which are crucial for the development and maintenance of alcohol use disorders (AUD). Here, we developed a novel high-throughput (HT) assay to quantify mitochondrial and neuronal toxicity in human DA neurons from induced pluripotent stem cells (iPSCs). The assay, dubbedmitochondrialneuronalhealth (MNH) assay, combines live-cell measurement of mitochondrial membrane potential (MMP) with quantification of neuronal branching complexity post-fixation. Using the MNH assay, we demonstrated that chronic ethanol exposure in human iPSC-derived DA neurons decreases MMP and branching complexity in a dose-dependent manner. The toxic effect of ethanol on DA neurons was already detectable after 1 hour of exposure, and occurred similarly in DA neurons derived from healthy individuals and from patients with AUD. We next used the MNH assay to carry out a proof-of-concept compound screening using FDA-approved drugs. We identified potential candidate drugs modulating acute ethanol toxicity in human DA neurons. Among these drugs, flavoxate and disulfiram influenced mitochondrial neuronal health independently from ethanol, leading to amelioration and worsening, respectively. Altogether, we developed an HT assay to probe human mitochondrial neuronal health and used it to assess ethanol neurotoxicity and to identify modulating agents. The MNH assay represents an effective new tool for discovering modulators of mitochondrial neuronal health and toxicity in live human neurons.
Cycle network model of Prostaglandin H Synthase-1
Authors: Goltsov Alexey , Swat Maciej , Peskov Kirill , Kosinsky Yuri 
Published: August 2020

AbstractThe kinetic model of Prostaglandin H Synthase-1 (PGHS-1) was developed to investigate its complex network kinetics and non-steroidal anti-inflammatory drugs (NSAIDs) efficacy in differentin vitroandin vivoconditions. To correctly describe the complex mechanism of PGHS-1 catalysis, we developed a microscopic approach to modelling of intricate network dynamics of 35 intraenzyme reactions among 24 intermediate states of the enzyme. The developed model quantitatively describes interconnection between cyclooxygenase and peroxidase enzyme activities; substrate (arachidonic acid, AA) and reducing cosubstrate competitive consumption; enzyme self-inactivation; autocatalytic role of AA; enzyme activation threshold, and synthesis of intermediate PGG2and final PGH2products under wide experimental conditions. In the paper we provided the detailed description of the enzyme catalytic cycle, model calibration based on a series ofin vitrokinetic data and model validation using experimental data on the regulatory properties of PGHS-1.The validated model of PGHS-1 with a unified set of kinetic parameters is applicable forin silicoscreening and prediction of the inhibition effects of NSAIDs and their combination on the balance of pro-thrombotic (thromboxane) and anti-thrombotic (prostacyclin) prostaglandin biosynthesis in platelets and endothelial cells expressing PGHS-1.
Mean-field models for EEG/MEG: from oscillations to waves
Authors: Byrne Á. , Ross James , Nicks Rachel , Coombes Stephen 
Published: August 2020

AbstractNeural mass models have been actively used since the 1970s to model the coarse-grained activity of large populations of neurons. They have proven especially fruitful for understanding brain rhythms. However, although motivated by neurobiological considerations they are phenomeno-logical in nature, and cannot hope to recreate some of the rich repertoire of responses seen in real neuronal tissue. Here we consider a simple spiking neuron network model that has recently been shown to admit to an exact mean-field description for both synaptic and gap-junction interactions. The mean-field model takes a similar form to a standard neural mass model, with an additional dynamical equation to describe the evolution of population synchrony. As well as reviewing the origins of thisnext generationmass model we discuss its extension to describe an idealised spatially extended planar cortex. To emphasise the usefulness of this model for EEG/MEG modelling we show how it can be used to uncover the role of local gap-junction coupling in shaping large scale synaptic waves.
Protein arginine methyltransferase 5 promotes metastasis via enhancing EGFR transcription and modulating AKT1 activation by methylation
Authors: Huang Lei , Zhang Xiao-Ou , Verdejo-Torres Odette , Wigglesworth Kim , Sun Xiaomei , Sallis Benjamin , Moon Daniel , Huang Tingting , Rozen Esteban , Wang Gang , Zhang Lei , Shohet Jason , Lee Mary M. , Wu Qiong 
Published: August 2020

AbstractProtein arginine methyltransferase 5 (PRMT5) regulates a wide range of physiological processes, including cancer cell proliferation and metastasis, by generating symmetric di-methyl-arginine marks on histones and non-histone proteins. Here, we report that PRMT5 directly regulates epidermal growth factor receptor (EGFR) transcription to control EGF stimulated EGFR signaling. Furthermore, PRMT5 modulates protein kinase B (AKT) activation by methylation of AKT1 Arg 15, which is required for its subsequent phosphorylation at AKT1 Thr 308 and Ser 473. The PRMT5/EGFR/AKT axis converges to regulate transcription factors ZEB1, SNAIL, and TWIST1 to promote the epithelial-mesenchymal transition (EMT), in the manner that EGFR and AKT1 compensate each other to support tumor cell invasion and metastasis. Inhibiting PRMT5 methyltransferase activity with a small molecule inhibitor attenuated primary tumor growth and prevented hepatic metastasis in aggressivein vivotumor models. Collectively, our results support the use of PRMT5 based therapies for metastatic cancer.
Alteration of mucins in the submandibular gland during aging in mice
Authors: Kameyama Akihiko , Thet Tin Wai Wai , Nishijima Risa , Yamakoshi Kimi 
Published: August 2020

AbstractObjectiveMucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene. This study aimed to characterize the changes in the mucins produced in submandibular gland (SMG) during the aging process.MethodsSMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME). Subsequently, the membranes were stained with AB or blotted with MAL-II lectin. The SMME membranes stained with AB were subjected to densitometric analysis and glycan analysis. The detailed structures of O-glycan were investigated by MS/MS spectra.ResultsThe SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging. Additionally, age-specific mucin began to be detected at about 12 months of age. A mucin expressed throughout life and age-specific mucin had the same mass of major glycans but different structures.Furthermore, the proportion of mucin glycan species expressed throughout life changed during the aging process, and aging tended to decrease the proportion of fucosylated glycans and increase the proportion of sialoglycans.ConclusionThere are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process. The proportion of glycan species of mucin expressed throughout life also changes during the aging process.HighlightsThree secreted mucins with different glycan profiles are detected in SMG using SMME.Each mucin has its own peak production age during the aging process.Age-specific mucin begins to be detected at about 12 months of age.Same mass of major glycans but different structures in mucins expressed throughout life vs. age-specific mucins.Proportion of mucin glycan species expressed throughout life changes during aging.
Kinesin-1 motility traced by an activity-based precipitating dye
Authors: Angerani Simona , Lindberg Eric , Klena Nikolai , Bleck Christopher K. E. , Aumeier Charlotte , Winssinger Nicolas 
Published: August 2020

AbstractKinesin-1 is a processive motor protein that uses ATP-derived energy to transport a variety of intracellular cargoes toward the cell periphery. As tracks for cargo delivery, kinesin-1 uses a subset of microtubules within the dense microtubule network. It is still debated what defines the specific binding of kinesin-1 to a subset of microtubules. Therefore, the ability to visualize and monitor kinesin transport in live cells is critical to study the myriad of functions associated with cargo trafficking. Herein we report the discovery of a fluorogenic small molecule substrate for kinesin-1 that yields a precipitating dye. The activity of kinesin-1 thus leaves a fluorescent trail along its walking path and can be visualized without loss of signal due to diffusion. Kinesin-1 specific transport of cargo from the Golgi appears as trails of fluorescence over time.
Single cell 3’UTR analysis identifies changes in alternative polyadenylation throughout neuronal differentiation and in autism
Authors: Göpferich Manuel , George Nikhil Oommen , Muelas Ana Domingo , Bizyn Alex , Pascual Rosa , Fijalkowska Daria , Kalamakis Georgios , Müller Ulrike , Krijgsveld Jeroen , Mendez Raul , Fariñas Isabel , Huber Wolfgang , Anders Simon , Martin-Villalba Ana 
Published: August 2020

SUMMARYAutism spectrum disorder (ASD) is a neurodevelopmental disease affecting social behavior. Many of the high-confident ASD risk genes relate to mRNA translation. Specifically, many of these genes are involved in regulation of gene expression for subcellular compartmentalization of proteins1. Cis-regulatory motifs that often localize to 3’- and 5’-untranslated regions (UTRs) offer an additional path for posttranscriptional control of gene expression. Alternative cleavage and polyadenylation (APA) affect 3’UTR length thereby influencing the presence or absence of regulatory elements. However, APA has not yet been addressed in the context of neurodevelopmental disorders. Here we used single cell 3’end sequencing to examine changes in 3’UTRs along the differentiation from neural stem cells (NSCs) to neuroblasts within the adult brain. We identified many APA events in genes involved in neurodevelopment, many of them being high confidence ASD risk genes. Further, analysis of 3’UTR lengths in single cells from ASD and healthy individuals detected longer 3’UTRs in ASD patients. Motif analysis of modulated 3’UTRs in the mouse adult neurogenic lineage and ASD-patients revealed enrichment of the cytoplasmic and polyadenylation element (CPE). This motif is bound by CPE binding protein 4 (CPEB4). In human and mouse data sets we observed co-regulation of CPEB4 and the CPEB-binding synaptic adhesion molecule amyloid beta precursor-like protein 1 (APLP1). We show that mice deficient in APLP1 show aberrant regulation of APA, decreased number of neural stem cells, and autistic-like traits. Our findings indicate that APA is used for control of gene expression along neuronal differentiation and is altered in ASD patients.
Differential thermotolerance adaptation between species ofCoccidioides
Authors: Mead Heather L. , Hamm Paris S. , Shaffer Isaac N. , de Melo Teixeira Marcus , Wendel Christopher S. , Wiederhold Nathan P. , Thompson George R. , Muñiz-Salazar Raquel , Castañón-Olivares Laura Rosio , Keim Paul , Plude Carmel , Terriquez Joel , Galgiani John N. , Orbach Marc J. , Barker Bridget M. 
Published: August 2020

AbstractCoccidioidomycosis, or Valley fever, is caused by two species of dimorphic fungi. Based on molecular phylogenetic evidence, the genusCoccidioidescontains two reciprocally monophyletic species:C. immitisandC. posadasii.However, phenotypic variation between species has not been deeply investigated. We therefore explored differences in growth rate under various conditions. A collection of 39C. posadasiiand 46C. immitisisolates, representing the full geographical range of the two species, were screened for mycelial growth rate at 37°C and 28°C on solid media. The radial growth rate was measured over 16 days on yeast extract agar. A linear mixed effect model was used to compare the growth rate ofC. posadasiiandC. immitisat 37°C and 28°C respectively.C. posadasiigrew significantly faster at 37°C, when compared toC. immitis;whereas both species had similar growth rates at 28°C. These results indicate thermotolerance differs between these two species. As the ecological niche has not been well-described forCoccidioidesspp., and disease variability between species has not been shown, the evolutionary pressure underlying the adaptation is unclear. However, this research reveals the first significant phenotypic difference between the two species that directly applies to ecological and clinical research.
Significantly improving the quality of genome assemblies through curation
Authors: Howe Kerstin , Chow William , Collins Joanna , Pelan Sarah , Pointon Damon-Lee , Sims Ying , Torrance James , Tracey Alan , Wood Jonathan 
Published: August 2020

AbstractBackgroundGenome sequence assemblies provide the basis for our understanding of biology. Generating error-free assemblies is therefore the ultimate, but sadly still unachieved goal of a multitude of research projects. Despite the ever-advancing improvements in data generation, assembly algorithms and pipelines, no automated approach has so far reliably generated near error-free genome assemblies for eukaryotes.ResultsWhilst working towards improved data sets and fully automated pipelines, assembly evaluation and curation is actively employed to bridge this shortcoming and significantly reduce the number of assembly errors. In addition to this increase in product value, the insights gained from assembly curation are fed back into the automated assembly strategy and contribute to notable improvements in genome assembly quality.ConclusionsWe describe our tried and tested approach for assembly curation using gEVAL, the genome evaluation browser. We outline the procedures applied to genome curation using gEVAL and also our recommendations for assembly curation in an gEVAL-independent context to facilitate the uptake of genome curation in the wider community.
Regulated delivery controls Drosophila Hedgehog, Wingless and Decapentaplegic signaling
Authors: Hatori Ryo , Kornberg Thomas B. 
Published: August 2020

AbstractMorphogen signaling proteins disperse across tissues to activate signal transduction in target cells. We investigated dispersion of Hedgehog (Hh), Wingless (Wg), and Bone morphogenic protein homolog Decapentaplegic (Dpp) in the Drosophila wing imaginal disc, and found that delivery to targets is regulated. Cells take up <5% Hh produced, and neither amounts taken up nor extent of signaling changes under conditions of Hh production from 50-200% normal amounts. Similarly, cells take up <25% Wg produced, and variation in Wg production from 50-700% normal has no effect on amounts taken up or signaling. Similar properties were observed for Dpp. Wing disc-produced Hh signals to disc-associated tracheal and myoblast as well as an approximately equal number of disc cells, but the extent of signaling in the disc is unaffected by the presence or absence of the tracheal cells and myoblasts. These findings show that target cells do not take up signaling proteins from a common pool and that both the amount and destination of delivered morphogens are regulated..SummaryThe extent of Hh, Wg, and Dpp signaling is independent of the amount of signal produced or the number of recipient cells.