bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased sensitivity of SARS-CoV-2 to type III interferon in human intestinal epithelial cells
Authors: Kee Carmon , Metz-Zumaran Camila , Doldan Patricio , Guo Cuncai , Stanifer Megan L. , Boulant Steeve 
Published: June 2021

AbstractThe coronavirus SARS-CoV-2 caused the COVID-19 global pandemic leading to 3.5 million deaths worldwide as of June 2021. The human intestine was found to be a major viral target which could have a strong impact on virus spread and pathogenesis since it is one of the largest organs. While type I interferons (IFNs) are key cytokines acting against systemic virus spread, in the human intestine type III IFNs play a major role by restricting virus infection and dissemination without disturbing homeostasis. Recent studies showed that both type I and III IFNs can inhibit SARS-CoV-2 infection, but it is not clear if one IFN controls SARS-CoV-2 infection of the human intestine better or with a faster kinetics. In this study, we could show that both type I and III IFNs possess antiviral activity against SARS-CoV-2 in human intestinal epithelial cells (hIECs), however type III IFN is more potent. Shorter type III IFN pretreatment times and lower concentrations were required to efficiently reduce virus load when compared to type I IFNs. Moreover, type III IFNs significantly inhibited SARS-CoV-2 even 4 hours post-infection and induced a long-lasting antiviral effect in hIECs. Importantly, the sensitivity of SARS-CoV-2 to type III IFNs was virus-specific since type III IFN did not control VSV infection as efficiently. Together these results suggest that type III IFNs have a higher potential for IFN-based treatment of SARS-CoV-2 intestinal infection as compared to type I IFNs.
NEST Desktop - An educational application for neuroscience
Authors: Spreizer Sebastian , Senk Johanna , Rotter Stefan , Diesmann Markus , Weyers Benjamin 
Published: June 2021

AbstractSimulation software for spiking neuronal network models matured in the past decades regarding performance and flexibility. But the entry barrier remains high for students and early career scientists in computational neuroscience since these simulators typically require programming skills and a complex installation. Here, we describe an installation-free Graphical User Interface (GUI) running in the web browser, which is distinct from the simulation engine running anywhere, on the student’s laptop or on a supercomputer. This architecture provides robustness against technological changes in the software stack and simplifies deployment for self-education and for teachers. Our new open source tool, NEST Desktop, comprises graphical elements for creating and configuring network models, running simulations, and visualizing and analyzing the results. NEST Desktop allows students to explore important concepts in computational neuroscience without the need to learn a simulator control language before. Our experiences so far highlight that NEST Desktop helps advancing both quality and intensity of teaching in computational neuroscience in regular university courses. We view the availability of the tool on public resources like the European ICT infrastructure for neuroscience EBRAINS as a contribution to equal opportunities.Significance StatementThe graphical user interface NEST Desktop makes neuronal network simulations accessible to non-programmers. It facilitates the interactive exploration of neuronal network models by integrating the whole workflow of wiring up the setup, simulating the neuronal dynamics, and analyzing the recorded activity data into a single tool. NEST Desktop effectively supports teaching the concepts and methods of computational neuroscience. Due to its installation-free web-based implementation, it is in particularly suitable for online courses.
Deciphering Tumour Tissue Organization by 3D Electron Microscopy and machine learning
Authors: de Senneville Baudouin Denis , Khoubai Fatma Zohra , Bevilacqua Marc , Labedade Alexandre , Flosseau Kathleen , Chardot Christophe , Branchereau Sophie , Ripoche Jean , Cairo Stefano , Gontier Etienne , Grosset Christophe F. 
Published: June 2021

ABSTRACTDespite recent progress in the characterization of tumour components, the tri-dimensional (3D) organization of this pathological tissue and the parameters determining its internal architecture remain elusive. Here, we analysed the spatial organization of patient-derived xenograft tissues generated from hepatoblastoma, the most frequent childhood liver tumour, by serial block-face scanning electron microscopy using an integrated workflow combining 3D imaging, manual and machine learning-based semi-automatic segmentations, mathematics and infographics. By digitally reconstituting an entire hepatoblastoma sample with a blood capillary, a bile canaliculus-like structure, hundreds of tumour cells and their main organelles (e.g. cytoplasm, nucleus, mitochondria), we report unique 3D ultrastructural data about the organization of tumoral tissue. We found that the size of hepatoblastoma cells correlates with the size of their nucleus, cytoplasm and mitochondrial mass. We also discovered that the blood capillary controls the planar alignment and size of tumour cells in their 3D milieu. Finally, a set of tumour cells polarized in the direction of a hot spot corresponding to a bile canaliculus-like structure. In conclusion, this pilot study allowed the identification of bioarchitectural parameters that shape the internal and spatial organization of tumours, thus paving the way for new investigations in an emerging field that we call ‘onconanotomy’.
Genomic features of Mycobacterium avium subsp. hominissuis isolated from pigs in Japan
Authors: Komatsu Tetsuya , Ohya Kenji , Ota Atsushi , Nishiuchi Yukiko , Yano Hirokazu , Matsuo Kayoko , Odoi Justice Opare , Suganuma Shota , Sawai Kotaro , Hasebe Akemi , Asai Tetsuo , Yanai Tokuma , Fukushi Hideto , Wada Takayuki , Yoshida Shiomi , Ito Toshihiro , Arikawa Kentaro , Kawai Mikihiko , Ato Manabu , Baughn Anthony D , Iwamoto Tomotada , Maruyama Fumito 
Published: June 2021

AbstractMycobacterium avium subsp. hominissuis (MAH) is one of the most important agents causing non-tuberculosis mycobacterial infection in humans and pigs. Genome analysis on MAH of human isolates has been proceeding, however, those of pigs are limited despite its potential source of infection to human. In the current study, we obtained 30 draft genome sequences of MAH of pigs reared in Japan. The 30 draft genomes consisted of 4,848,678 – 5,620,788 bp length, 4,652 – 5,388 coding genes and 46 – 75 (Med: 47) tRNAs. All isolates had restriction modification associated genes and 185 – 222 predicted virulence genes. Two isolates had tRNA arrays and one isolate had a clustered regularly interspaced short palindromic repeat (CRISPR) region. Our results will be useful for evaluation of the ecology of MAH by providing a foundation for genome-based epidemiological studies.
Evaluation of US state pollinator plans using 3 evidence-based policymaking frameworks
Authors: Whitney Kaitlin Stack , Stringer Briana Burt 
Published: June 2021

AbstractAfter the US federal government created a national pollinator protection plan in 2015, many states followed with their own. Since their goal is to promote pollinating insect conservation, we wanted to know whether the state plans are using best practices for evidence-based science policy. In early 2019 we found and downloaded every existing, publicly available US state pollinator protection plan. We then used content analysis to assess the goals, scope, and implementation of state-level pollinator protection plans across the US. This analysis was conducted using three distinct frameworks for evidence-based policymaking: US Department of Interior Adaptive Resources Management (ARM), US Environmental Protection Agency management pollinator protection plan (MP3) guidance, and Pew Trusts Pew-MacAthur Results First Project elements of evidence-based state policymaking (PEW) framework. Then we scored them using the framework criteria, to assess whether the plans were using known best practices for evidence based policymaking. Of the 31 states with a state pollinator plan, Connecticut was the state with the lowest total score across the three evaluation frameworks. The state with the highest overall scores, across the three frameworks, was Missouri. Most states did not score highly on the majority of the frameworks. Overall, many state plans were lacking policy elements that address monitoring, evaluation, and adjustment. These missing elements impact states’ ability to achieve their conservation goals. Our results indicate that states can improve their pollinator conservation policies to better match evidence-based science policy guidance, regardless of which framework is used.
Developing and deploying an integrated workshop curriculum teaching computational skills for reproducible research
Authors: Lapp Zena , Sovacool Kelly L. , Lesniak Nick , King Dana , Barnier Catherine , Flickinger Matthew , Krüger Jule , Armour Courtney R. , Lapp Maya M. , Tallant Jason , Diao Rucheng , Oneka Morgan , Tomkovich Sarah , Anderson Jacqueline Moltzau , Lucas Sarah K. , Schloss Patrick D. 
Published: June 2021

SummaryInspired by well-established material and pedagogy provided by The Carpentries (Wilson 2016), we developed a two-day workshop curriculum that teaches introductory R programming for managing, analyzing, plotting and reporting data using packages from the tidyverse (Wickham et al. 2019), the Unix shell, version control with git, and GitHub. While the official Software Carpentry curriculum is comprehensive, we found that it contains too much content for a two-day workshop. We also felt that the independent nature of the lessons left learners confused about how to integrate the newly acquired programming skills in their own work. Thus, we developed a new curriculum that aims to teach novices how to implement reproducible research principles in their own data analysis. The curriculum integrates live coding lessons with individual-level and group-based practice exercises, and also serves as a succinct resource that learners can reference both during and after the workshop. Moreover, it lowers the entry barrier for new instructors as they do not have to develop their own teaching materials or sift through extensive content. We developed this curriculum during a two-day sprint, successfully used it to host a two-day virtual workshop with almost 40 participants, and updated the material based on instructor and learner feedback. We hope that our new curriculum will prove useful to future instructors interested in teaching workshops with similar learning objectives.
Seascape genomics reveals population structure and local adaptation in a widespread coral reef snail,Coralliophila violacea(Kiener, 1836)
Authors: Simmonds Sara E. , Cheng Samantha H. , Fritts-Penniman Allison L. , Mahardika Gusti Ngurah , Barber Paul H. 
Published: June 2021

ABSTRACTLocal adaptation to different environments may reinforce neutral evolutionary divergence, especially in populations in the periphery of a species’ geographic range. Seascape genomics (high-throughput genomics coupled with ocean climate databases) facilitates the exploration of neutral and adaptive variation in concert, developing a clearer picture of processes driving local adaptation in marine populations. This study used a seascape genomics approach to test the relative roles of neutral and adaptive processes shaping population divergence of a widespread coral reef snail,Coralliophila violacea. We collectedC. violaceafrom colonies of their coral host (Poritesspp.) at ten locations spanning a large portion of their geographic range. We used RAD-seq to investigate possible local adaptation via genetic-environmental associations with five ocean climate variables. Four genetic partitions were concordant with regions previously observed in mtDNA (Indian Ocean, Coral Triangle, and Hawaiian Islands), with the addition of Vietnam and varying isolation and admixture levels. We identified outlier loci (FDR = 0.10,N= 72) among individual localities and between regions (FDR = 0.10,N= 34), suggesting that some loci are putatively under divergent selection. Association analyses showed that the two strongest drivers of local adaptation were the annual range and mean of sea surface temperature. Populations that experience lower sea surface temperatures at the periphery ofC. violacea’sgeographic range drive these associations. Our results show that local adaptation to different environments likely reinforces neutral divergence, especially in peripheral populations.
A new adaptive procedure for estimating perceptual thresholds: the effects of observer bias and its correction
Authors: Fioravanti Chiara , Braun Christoph , Lindner Axel , Ruiz Sergio , Sitaram Ranganatha , Kajal Diljit Singh 
Published: June 2021

AbstractAdaptive threshold estimation procedures sample close to a subject’s perceptual threshold by dynamically adapting the stimulation based on the subject’s performance. Yet, perceptual thresholds not only depend on the observers’ sensory capabilities but also on any bias in terms of their expectations and response preferences, thus distorting the precision of the threshold estimates. Using the framework of signal detection theory (SDT), independent estimates of both, an observer’s sensitivity and internal processing bias can be delineated from threshold estimates. While this approach is commonly available for estimation procedures engaging the method of constant stimuli (MCS), correction procedures for adaptive methods (AM) are only scarcely applied. In this article, we introduce a new AM that takes individual biases into account, and that allows for a bias-corrected assessment of subjects’ sensitivity. This novel AM is validated with simulations and compared to a typical MCS-procedure, for which the implementation of bias correction has been previously demonstrated.Comparing AM and MCS demonstrates the viability of the presented AM. Besides its feasibility, the results of the simulation reveal both, advantages, and limitations of the proposed AM. The procedure has considerable practical implications, in particular for the design of shaping procedures in sensory training experiments, in which task difficulty has to be constantly adapted to an observer’s performance, to improve training efficiency.
15 years of introgression studies: quantifying gene flow across Eukaryotes
Authors: Dagilis Andrius J. , Peede David , Coughlan Jenn M. , Jofre Gaston I. , D’Agostino Emmanuel R. R. , Mavengere Heidi , Tate Alexander D. , Matute Daniel R. 
Published: June 2021

ABSTRACTWith the rise of affordable next generation sequencing technology, introgression — or the exchange of genetic materials between taxa — is widely perceived to be a ubiquitous phenomenon in nature. Although this claim is supported by several keystone studies, no thorough assessment on the frequency of introgression in nature has been performed to date. In this manuscript, we aim to address this knowledge gap by providing a meta-analysis of the most comprehensive survey of introgression studies in Eukaryotes to date (724 papers with claims of introgression). We first examined the evidence given to support introgression, and if/how the lines of evidence have changed across time. We then collated a single statistic, Patterson’sD, that quantifies the strength of introgression across 123 studies to further assess how taxonomic group, divergence time, and aspects of life history influence introgression. We find three main results. Studies on introgression are much more frequent in plants and mammals than any other taxonomic group. The study of introgression has shifted from a largely qualitative assessment of whether introgression happens, to a focus on when and how much introgression has occurred across taxa. The most often used introgression statistic, Patterson’sD, shows several intriguing patterns suggesting introgression reports may be biased by both differences in reporting criteria and sequencing technology, but may also differ across taxonomic systems and throughout the process of speciation. Together, these results suggest the need for a unified approach to quantifying introgression in natural communities, and highlight important areas of future research that can be better assessed once this unified approach is met.
Cyanolichen microbiome contains novel viruses that encode genes to promote microbial metabolism
Authors: Ponsero Alise J. , Hurwitz Bonnie L. , Magain Nicolas , Miadlikowska Jolanta , Lutzoni François , U’Ren Jana M. 
Published: June 2021

AbstractLichen thalli are formed through the symbiotic association of a filamentous fungus and photosynthetic green alga and/or cyanobacterium. Recent studies have revealed lichens also host highly diverse communities of secondary fungal and bacterial symbionts, yet few studies have examined the viral component within these complex symbioses. Here, we describe viral biodiversity and functions in cyanolichens collected from across North America and Europe. As current machine learning viral-detection tools are not trained on complex eukaryotic metagenomes, we first developed efficient methods to remove eukaryotic reads prior to viral detection and a custom pipeline to validate viral contigs predicted with three machine-learning methods. Our resulting high-quality viral data illustrate that every cyanolichen thallus contains diverse viruses that are distinct from viruses in other terrestrial ecosystems. In addition to cyanobacteria, predicted viral hosts include other lichen-associated bacterial lineages and algae, although a large fraction of viral contigs had no host prediction. Functional annotation of cyanolichen viral sequences reveals numerous viral-encoded auxiliary metabolic genes (AMGs) involved in amino acid, nucleotide, and carbohydrate metabolism, including AMGs for secondary metabolism (antibiotics and antimicrobials) and fatty acid biosynthesis. Overall, the diversity of cyanolichen AMGs suggests that viruses may alter microbial interactions within these complex symbiotic assemblages.
A type VII secretion system in Group B Streptococcus mediates cytotoxicity and virulence
Authors: Spencer BL , Tak U , Mendonça JC , Nagao PE , Niederweis M , Doran KS 
Published: June 2021

AbstractType VII secretion systems (T7SS) have been identified in Actinobacteria and Firmicutes and have been shown to secrete effector proteins with functions in virulence, host toxicity, or interbacterial killing in a few genera. Bioinformatic analysis indicates that Group B streptococcal (GBS) isolates encode four distinct subtypes of T7SS machinery, three of which encode adjacent putative T7SS effectors with WXG and LXG motifs. However, the function of T7SS in GBS pathogenesis is not known. Here we show that the most abundant GBS T7SS subtype is important for virulence and cytotoxicity in brain endothelium and that these phenotypes are dependent on the WXG100 effector EsxA. We further show that the WXG motif is required for cytotoxicity in brain endothelium and that EsxA is a pore-forming protein. This work reveals the importance of a T7SS in host–GBS interactions and has implications for the functions of T7SS effectors in other Gram-positive bacteria.
Restoring statistical validity in group analyses of motion-corrupted MRI data
Authors: Lutti Antoine , Corbin Nadège , Ashburner John , Ziegler Gabriel , Draganski Bogdan , Phillips Christophe , Kherif Ferath , Callaghan Martina F. , Di Domenicantonio Giulia 
Published: June 2021

AbstractMotion during the acquisition of magnetic resonance imaging (MRI) data degrades image quality, hindering our capacity to characterize disease in patient populations. Quality control procedures allow the exclusion of the most affected images from analysis. However, the criterion for exclusion is difficult to determine objectively and exclusion can lead to a suboptimal compromise between image quality and sample size. We provide an alternative, data-driven solution that assigns weights to each image, computed from an index of image quality using restricted maximum likelihood. We illustrate this method through the analysis of brain MRI data. The proposed method restores the validity of statistical tests, and performs near optimally in all brain regions, despite local effects of head motion. This method is amenable to the analysis of a broad type of MRI data and can accommodate any measure of image quality.
RASSF1A independence and early Galectin-1 upregulation in PIK3CA induced hepatocarcinogenesis: new therapeutic venues
Authors: Scheiter Alexander , Evert Katja , Reibenspies Lucas , Cigliano Antonio , Annweiler Katharina , Müller Karolina , Pöhmerer Laura-Maria-Giovanna , Itzel Timo , Materna-Reichelt Silvia , Coluccio Andrea , Honarnejad Kamran , Teufel Andreas , Brochhausen Christoph , Dombrowski Frank , Chen Xin , Evert Matthias , Calvisi Diego F. , Utpatel Kirsten 
Published: June 2021

AbstractAberrant activation of the PI3K/AKT/mTOR and Ras/Mitogen-Activated Protein Kinase pathways is a hepatocarcinogenesis hallmark. In a subset of hepatocellular carcinomas (HCC), PI3K/AKT/mTOR signaling dysregulation depends on PIK3CA mutations, while RAS/MAPK activation is partly attributed to promoter methylation of the tumor suppressorRASSF1A. To evaluate a possible co-carcinogenic effect of PIK3CA activation andRASSF1Aknockout, plasmids expressing oncogenic forms of PIK3CA (E545K or H1047R mutants) were delivered to the liver of RASSF1A knockout and wildtype mice by hydrodynamic tail vein injection combined with Sleeping Beauty–mediated somatic integration. Transfection of either PIK3CA E545K or H1047R mutants sufficed to induce hepatocellular carcinomas in mice irrespective ofRASSF1Amutational background. The related tumors displayed a lipogenic phenotype with upregulation of Fatty acid synthase and Stearoyl-CoA desaturase-1 (SCD1). Galectin-1, which was commonly upregulated in preneoplastic lesions and tumors, emerged as a regulator of SCD1. Co-inhibitory treatment with PIK3CA inhibitors and the Galectin-1 inhibitor OTX-008 resulted in synergistic cytotoxicity in human HCC cell lines, suggesting novel therapeutic venues.Graphical AbstractHydrodynamic tail vein injection of Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutant forms E545K and H1047R induces stepwise hepatocarcinogenesis in mice, independent of Ras association domain-containing protein 1 (RASSF1A) status. Gene expression analyses revealed an early increase in Galectin-1, which regulates the lipogenic enzyme Stearoyl-CoA desaturase-1 (SCD1). PIK3CA- and Galectin1 inhibitors act synergistically, pointing at novel therapeutic strategies.