bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating brain mechanisms underlying natural reading by co-registering eye tracking with combined EEG and MEG
Authors: Weiss Béla , Dreyer Felix , Fonteneau Elisabeth , van Casteren Maarten , Hauk Olaf 
Published: July 2021

AbstractLinking brain and behavior is one of the great challenges in cognitive neuroscience. Ultimately, we want to understand how the brain processes information to guide every-day behavior. However, most neuroscientific studies employ very simplistic experimental paradigms whose ecological validity is doubtful. Reading is a case in point, since most neuroscientific studies to date have used unnatural word-by-word stimulus presentation and have often focused on single word processing. Previous research has therefore actively avoided factors that are important for natural reading, such as rapid self-paced voluntary saccadic eye movements. Recent methodological developments have made it possible to deal with associated problems such as eye movement artefacts and the overlap of brain responses to successive stimuli, using a combination of eye-tracking and neuroimaging. A growing number of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are successfully using this methodology. Here, we provide a proof-of-concept that this methodology can be applied to combined EEG and magnetoencephalography (MEG) data. Our participants naturally read 4-word sentences that could end in a plausible or implausible word while eye-tracking, EEG and MEG were being simultaneously recorded. Eye-movement artefacts were removed using independent-component analysis. Fixation-related potentials and fields for sentence-final words were subjected to minimum-norm source estimation. We detected an N400-type brain response in our EEG data starting around 200 ms after fixation of the sentence-final word. The brain sources of this effect, estimated from combined EEG and MEG data, were mostly located in left temporal lobe areas. We discuss the possible use of this method for future neuroscientific research on language and cognition.
Structural and mechanistic insight into CRISPR-Cas9 inhibition by anti-CRISPR protein AcrIIC4
Authors: Hwang Sungwon , Pan Chuxi , Garcia Bianca , Davidson Alan R. , Moraes Trevor F. , Maxwell Karen L. 
Published: July 2021

ABSTRACTPhages, plasmids, and other mobile genetic elements express inhibitors of CRISPR-Cas immune systems, known as anti-CRISPR proteins, to protect themselves from targeted destruction. These anti-CRISPRs have been shown to function through very diverse mechanisms. In this work we investigate the activity of an anti-CRISPR isolated from a prophage in Haemophilus parainfluenzae that blocks CRISPR-Cas9 DNA cleavage activity. We determine the three-dimensional crystal struture of AcrIIC4 and show that it binds to the Cas9 Recognition Domain. This binding does not prevent the Cas9-anti-CRISPR complex from interacting with target DNA but does inhibit DNA cleavage. AcrIIC4 likely acts by blocking the conformational changes that allow the HNH and RuvC endonuclease domains to contact the DNA sites to be nicked.
Myoparr-associated and -independent multiple roles of heterogeneous nuclear ribonucleoprotein K during skeletal muscle cell differentiation
Authors: Hitachi Keisuke , Kiyofuji Yuri , Nakatani Masashi , Tsuchida Kunihiro 
Published: July 2021

AbstractRNA-binding proteins (RBPs) regulate cell physiology via the formation of ribonucleic-protein complexes with coding and non-coding RNAs. RBPs have multiple functions in the same cells; however, the precise mechanism through which their pleiotropic functions are determined remains unknown. In this study, we revealed the multiple inhibitory functions of heterogeneous nuclear ribonucleoprotein K (hnRNPK) for myogenic differentiation. We first identified hnRNPK as a lncRNAMyoparrbinding protein. Gain- and loss-of-function experiments showed that hnRNPK repressed the expression ofmyogeninat the transcriptional level. The hnRNPK-binding region ofMyoparrwas required to repressmyogeninexpression. Moreover, hnRNPK repressed the expression of a set of genes coding for aminoacyl-tRNA synthetases in aMyoparr-independent manner. Mechanistically, hnRNPK regulated the eIF2α/Atf4 pathway, one branch of the intrinsic pathways of the endoplasmic reticulum sensors, in differentiating myoblasts. Thus, our findings demonstrate that hnRNPK plays lncRNA-associated and - independent multiple roles during myogenic differentiation, indicating that the analysis of lncRNA-binding proteins will be useful for elucidating both the physiological functions of lncRNAs and the multiple functions of RBPs.
Co‑cultivation of the anaerobic fungusCaecomyces churroviswithMethanobacterium bryantiienhances transcription of carbohydrate binding modules
Authors: Brown Jennifer L. , Swift Candice L. , Mondo Stephen , Seppala Susanna , Salamov Asaf , Singan Vasanth , Henrissat Bernard , Henske John K. , Lee Samantha , He Guifen , Yan Mi , Barry Kerrie , Grigoriev Igor V. , O’Malley Michelle A. 
Published: July 2021

AbstractAnaerobic fungi and methanogenic archaea are two classes of microorganisms found in the rumen microbiome that metabolically interact during lignocellulose breakdown. Here, stable synthetic co-cultures of the anaerobic fungusCaecomyces churrovisand the methanogenMethanobacterium bryantii(not native to the rumen) were formed, demonstrating that microbes from different environments can be paired based on metabolic ties. Transcriptional and metabolic changes induced by methanogen co-culture were evaluated inC. churrovisacross a variety of substrates to identify mechanisms that impact biomass breakdown and sugar uptake. A high-quality genome ofC. churroviswas obtained and annotated, which is the first sequenced genome of a non-rhizoid forming anaerobic fungus.C. churrovispossess an abundance of CAZymes and carbohydrate binding modules and, in agreement with previous studies of early-diverging fungal lineages, N6-methyldeoxyadenine (6mA) was associated with transcriptionally active genes. Co-culture with the methanogen increased overall transcription of CAZymes, carbohydrate binding modules, and dockerin domains in co-cultures grown on both lignocellulose and cellulose and caused upregulation of genes coding associated enzymatic machinery including carbohydrate binding modules in family 18 and dockerin domains across multiple growth substrates relative toC. churrovismonoculture. Two other fungal strains grown on a reed canary grass substrate in co-culture with the same methanogen also exhibited high log2fold change values for upregulation of genes encoding carbohydrate binding modules in families 1 and 18. Transcriptional upregulation indicated that co-culture of theC. churrovisstrain with a methanogen may enhance pyruvate formate lyase (PFL) function for growth on xylan and fructose and production of bottleneck enzymes in sugar utilization pathways, further supporting the hypothesis that co-culture with a methanogen may enhance certain fungal metabolic functions. Upregulation of CBM18 may play a role in fungal-methanogen physical associations and fungal cell wall development and remodeling.
Your head is there to move you around: Goal-driven models of the primate dorsal pathway
Authors: Mineault Patrick J , Bakhtiari Shahab , Richards Blake A , Pack Christopher C 
Published: July 2021

AbstractNeurons in the dorsal visual pathway of the mammalian brain are selective for motion stimuli, with the complexity of stimulus representations increasing along the hierarchy. This progression is similar to that of the ventral visual pathway, which is well characterized by artificial neural networks (ANNs) optimized for object recognition. In contrast, there are no image-computable models of the dorsal stream with comparable explanatory power. We hypothesized that the properties of dorsal stream neurons could be explained by a simple learning objective: the need for an organism to orient itself during self-motion. To test this hypothesis, we trained a 3D ResNet to predict an agent’s self-motion parameters from visual stimuli in a simulated environment. We found that the responses in this network accounted well for the selectivity of neurons in a large database of single-neuron recordings from the dorsal visual stream of non-human primates. In contrast, ANNs trained on an action recognition dataset through supervised or self-supervised learning could not explain responses in the dorsal stream, despite also being trained on naturalistic videos with moving objects. These results demonstrate that an ecologically relevant cost function can account for dorsal stream properties in the primate brain.
Reduced neutralization of SARS-CoV-2 B.1.617 variant by inactivated and RBD-subunit vaccine
Authors: Hu Jie , Wei Xiao-yu , Xiang Jin , Peng Pai , Xu Feng-li , Wu Kang , Luo Fei-yang , Jin Ai-shun , Fang Liang , Liu Bei-zhong , Wang Kai , Tang Ni , Huang Ai-Long 
Published: July 2021

AbstractCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.
Double nerve transfer to a single target muscle: experimental model in the upper extremity
Authors: Luft Matthias , Klepetko Johanna , Muceli Silvia , Ibáñez Jaime , Tereshenko Vlad , Festin Christopher , Längle Gregor , Politikou Olga , Maierhofer Udo , Farina Dario , Aszmann Oskar C. , Bergmeister Konstantin D. 
Published: July 2021

AbstractSurgical nerve transfers are used to efficiently treat peripheral nerve injuries, neuromas, phantom limb pain or improve bionic prosthetic control. Commonly, one donor nerve is transferred to one target muscle. However, the transfer of multiple nerves onto a single target muscle may increase the number of muscle signals for myoelectric prosthetic control and facilitate the treatment of multiple neuromas. Currently, no experimental models are available for multiple nerve transfers to a common target muscle in the upper extremity. This study describes a novel experimental model to investigate the neurophysiological effects of peripheral double nerve transfers. For this purpose, we developed a forelimb model to enable tension-free transfer of one or two donor nerves in the upper extremity. Anatomic dissections were performed to design the double nerve transfer model (n=8). In 62 male Sprague-Dawley rats the ulnar nerve of the antebrachium alone (n=30) or together with the anterior interosseus nerve (n=32) was transferred to reinnervate the long head of the biceps brachii. Before neurotization, the motor branch to the biceps’ long head was transected at the motor entry point and resected up to its original branch to prevent auto-reinnervation. In all animals, coaptation of both nerves to the motor entry point could be performed tension-free. Mean duration of the procedure was 49 ± 13 min for the single nerve transfer and 78 ± 20 min for the double nerve transfer. Twelve weeks after surgery, muscle response to neurotomy, behavioral testing, retrograde labeling and structural analyses were performed to assess reinnervation. These analyses indicated that all nerves successfully reinnervated the target muscle. No aberrant reinnervation was observed by the originally innervating nerve. Our observations suggest a minimal burden for the animal with no signs of functional deficit in daily activities or auto-mutilation in both procedures. Furthermore, standard neurophysiological analyses for nerve and muscle regeneration were applicable. This newly developed nerve transfer model allows for the reliable and standardized investigation of neural and functional changes following the transfer of multiple donor nerves to one target muscle.
Temporal regulation of Pten is essential for retina regeneration in zebrafish
Authors: Gupta Shivangi , Sharma Poonam , Chaudhary Mansi , Premraj Sharanya , Kaur Simran , Vijithkumar V , Ramachandran Rajesh 
Published: July 2021

AbstractUnlike mammals, zebrafish possess a remarkable ability to regenerate damaged retina after an acute injury. Retina regeneration in zebrafish involves the induction of Müller glia-derived progenitor cells (MGPCs) exhibiting stem cell-like characteristics, which are capable of restoring all retinal cell-types. Here, we explored the importance of Phosphatase and tensin homolog (Pten), a dual-specificity phosphatase and tumor suppressor during retina regeneration. The Pten undergo rapid downregulation in the Müller glia and is absent in MGPCs, which is essential to trigger Akt-mediated cell proliferation to cause retina regeneration. We found that the forced downregulation of Pten accelerates MGPCs formation, while its overexpression restricts the regenerative response. We observed that Pten regulates the proliferation of MGPCs not only through Akt pathway but also by Mmp9/Notch signaling. Mmp9-activity is essential to induce the proliferation of MGPCs in the absence of Pten. Lastly, we show that Pten expression is fine-tuned through Mycb/histone deacetylase1 and Tgf-β signaling. The present study emphasizes on the stringent regulation of Pten and its crucial involvement during the zebrafish retina regeneration.
The 3D enhancer network of the developing T cell genome is controlled by SATB1
Authors: Zelenka Tomas , Klonizakis Antonios , Tsoukatou Despina , Franzenburg Sören , Tzerpos Petros , Papamatheakis Dionysios-Alexandros , Tzonevrakis Ioannis-Rafail , Nikolaou Christoforos , Plewczynski Dariusz , Spilianakis Charalampos 
Published: July 2021

SummaryMechanisms of tissue-specific gene expression regulation via spatial coordination of gene promoters and distal regulatory elements are still poorly understood. We investigated the 3D genome organization of developing murine T cells and identified SATB1, a tissue-specific genome organizer, enriched at the anchors of promoter-enhancer chromatin loops. We assessed the function of SATB1 in T cell chromatin organization and compared it to the conventional genome organizer CTCF. SATB1 builds a more refined layer of genome organization upon a CTCF scaffold. To understand the regulatory implications of SATB1 loopscape structure, we generatedSatb1fl/flCd4-Cre+(Satb1cKO) conditional knockout animals which suffered from autoimmunity. We aimed to identify molecular mechanisms responsible for the deregulation of the immune system inSatb1cKO animals. H3K27ac HiChIP and Hi-C experiments indicated that SATB1 primarily mediates promoter-enhancer loops affecting master regulator genes (such asBcl6), the T cell receptor locus and adhesion molecule genes, collectively being critical for cell lineage specification and immune system homeostasis. Our findings unravel the function of a tissue-specific factor that controls transcription programs, via spatial chromatin arrangements complementary to the chromatin structure imposed by ubiquitously expressed genome organizers.
A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses
Authors: Meunier Thomas , Desmarets Lowiese , Bordage Simon , Bamba Moussa , Hervouet Kévin , Rouillé Yves , François Nathan , Decossas Marion , Bi Fézan Honora Tra , Lambert Olivier , Dubuisson Jean , Belouzard Sandrine , Sahpaz Sevser , Séron Karin 
Published: July 2021

ABSTRACTThe SARS-CoV-2 outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against HCoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and MERS-CoV, and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly, the antiviral activity of Pba depends on light exposure, and Pba was shown to inhibit virus-cell fusion by stiffening the viral membrane as demonstrated by cryo-electron microscopy. Moreover, Pba was shown to be broadly active against several other enveloped viruses, and reduced SARS-CoV-2 and MERS-CoV replication in primary human bronchial epithelial cells. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity that holds potential for COVID-19 therapy or disinfection of SARS-CoV-2 contaminated surfaces.
Structural covariance of amygdala subregions is associated with trait aggression and endogenous testosterone in healthy individuals
Authors: Göttlich Martin , Buades-Rotger Macià , Wiechert Juliana , Beyer Frederike , Krämer Ulrike M. 
Published: July 2021

AbstractMany studies point toward volume reductions in the amygdala as a potential neurostructural marker for trait aggression. However, most of these findings stem from clinical samples, rendering unclear whether the findings generalize to non-clinical populations. Furthermore, the notion of neural networks suggests that interregional correlations in grey matter volume (i.e., structural covariance) can explain individual differences in aggressive behavior beyond local univariate associations. Here, we tested whether structural covariance between amygdala subregions and the rest of the brain is associated with self-reported aggression in a large sample of healthy young students (n=263; 51% women). Salivary testosterone concentrations were measured for a subset of n=76 participants (45% women), allowing us to investigate the influence of endogenous testosterone on structural covariance. Aggressive individuals showed enhanced covariance between superficial amygdala (SFA) and dorsal anterior insula (dAI), but lower covariance between laterobasal amygdala (LBA) and dorsolateral prefrontal cortex (dlPFC). These structural patterns overlap with functional networks involved in the genesis and regulation of aggressive behavior, respectively. With increasing endogenous testosterone, we observed stronger structural covariance between centromedial amygdala (CMA) and medial prefrontal cortex in men and between CMA and orbitofrontal cortex in women. These results speak for structural covariance of amygdala subregions as a robust correlate of trait aggression in healthy individuals. Moreover, regions that showed structural covariance with the amygdala modulated by either testosterone or aggression did not overlap, speaking for a more complex role of testosterone in human social behavior rather than the simple assumption that testosterone only increases aggressiveness.
Serotonergic neural network related to behavioral inhibition system
Authors: Kojima Kazuho , Hirano Shigeki , Kimura Yasuyuki , Seki Chie , Ikoma Yoko , Takahata Keisuke , Ito Takehito , Yokokawa Keita , Hashimoto Hiroki , Kawamura Kazunori , Zhang Ming-Rong , Ito Hiroshi , Higuchi Makoto , Kuwabara Satoshi , Suhara Tetsuya , Yamada Makiko 
Published: July 2021

AbstractRationale The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. Objectives To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Results Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Conclusions Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.
SUPT3H-less SAGA coactivator can assemble and function without significantly perturbing RNA polymerase II transcription in mammalian cells
Authors: Fischer Veronique , Scheer Elisabeth , Lata Elisabeth , Morlet Bastian , Plassard Damien , Vincent Stéphane D. , Helmlinger Dominique , Devys Didier , Tora László 
Published: July 2021

AbstractCoactivator complexes regulate chromatin accessibility and transcription. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved coactivator complex. The core module scaffolds the entire SAGA complex and adopts a histone octamer-like structure, which consists of six histone fold domain (HFD)-containing proteins forming three histone fold (HF) pairs, to which the double HFD-containing SUPT3H adds an HF pair. Spt3, the yeast ortholog of SUPT3H, interacts genetically and biochemically with the TATA binding protein (TBP) and contributes to global RNA polymerase II (Pol II) transcription. Here we demonstrate that i) SAGA purified from human U2OS or mouse embryonic stem cells (mESC) can assemble without SUPT3H; ii) SUPT3H is not essential for mESC survival, iii) SUPT3H is required for mESC growth and self-renewal, and iv) the loss of SUPT3H from mammalian cells affects the transcription of only a specific subset of genes. Accordingly, in the absence of SUPT3H no major change in TBP accumulation at gene promoters was observed. Thus, SUPT3H is not required for the assembly of SAGA, TBP recruitment, or overall Pol II transcription, but plays a role in mESC growth and self-renewal. Our data further suggest that yeast and mammalian SAGA complexes contribute to transcription regulation by distinct mechanisms.