bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-view confocal microscopy enables multiple organ and whole organism live-imaging
Authors: Leroy Olivier , van Leen Eric , Girard Philippe , Villedieu Aurélien , Hubert Christian , Bosveld Floris , Bellaïche Yohanns , Renaud Olivier 
Published: May 2021

AbstractUnderstanding how development is coordinated in multiple tissues and gives rise to fully functional organs or whole organisms necessitates microscopy tools. Over the last decade numerous advances have been made in live-imaging, enabling high resolution imaging of whole organisms at cellular resolution. Yet, these advances mainly rely on mounting the specimen in agarose or aqueous solutions, precluding imaging of organisms whose oxygen uptake depends on ventilation. Here, we implemented a multi-view multi-scale microscopy strategy based on confocal spinning disk microscopy, called Multi-View confocal microScopy (MuViScopy). MuViScopy enables live-imaging of multiple organs with cellular resolution using sample rotation and confocal imaging without the need of sample embedding. We illustrate the capacity of MuViScopy by live-imagingDrosophila melanogasterpupal development throughout metamorphosis, highlighting how internal organs are formed and multiple organ development is coordinated. We foresee that MuViScopy will open the path to better understand developmental processes at the whole organism scale in living systems that necessitates gas exchange by ventilation.
TOPLESS promotes plant immunity by repressing auxin signaling and is targeted by the fungal effector Naked1
Authors: Navarrete Fernando , Gallei Michelle , Kornienko Aleksandra E. , Saado Indira , Chia Khong-Sam , Darino Martin A. , Khan Mamoona , Bindics Janos , Djamei Armin 
Published: May 2021

AbstractIn plants, the antagonism between growth and defense is hardwired by hormonal signaling. Perception of Pathogen Associated Molecular Patterns (PAMPs) from invading microorganisms inhibits auxin signaling and growth. Conversely, pathogens manipulate auxin signaling to promote disease, but how this hormone inhibits immunity is not fully understood.Ustilago maydisis a maize pathogen that induces auxin signaling in its host. We characterized anU. maydiseffector protein, Naked1 (Nkd1), that is translocated into the host nucleus. Through its native EAR motif, Nkd1 binds to the transcriptional co-repressors TOPLESS/TOPLESS related (TPL/TPRs) and prevents the recruitment of transcriptional repressors involved in hormonal signaling, leading to de-repression of auxin and jasmonate signaling. Moderate up-regulation of auxin signaling inhibits an early defense response, PAMP-triggered ROS burst. Thus, our findings establish a clear mechanism for auxin-induced pathogen susceptibility. Manipulation of TPL by Nkd1 is evolutionary well balanced as engineered Nkd1 variants with increased expression or increased EAR-mediated TPL/TPR binding trigger typical salicylic acid mediated defense reactions, leading to pathogen resistance.
Biological mechanisms of aging predict age-related disease multimorbidities in patients
Authors: Fraser Helen C , Kuan Valerie , Johnen Ronja , Zwierzyna Magdalena , Hingorani Aroon D , Beyer Andreas , Partridge Linda 
Published: May 2021

AbstractGenetic, environmental and pharmacological interventions into the aging process can confer resistance to a multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that mechanisms of aging might contribute to patterns of multimorbidity in humans, and hence could be targeted to prevent multiple conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation, and found strong, non-random associations between age-related diseases and aging mechanisms, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signalling pathway and activity of the ERK1/2 pathway played a significant role across multiple aging mechanisms and multiple, diverse age-related diseases. Mechanisms of aging therefore contribute to multiple age-related diseases and to patterns of human age-related multimorbidity, and could potentially be targeted to prevent more than one age-related condition in the same patient.
Fitness costs of female choosiness in a socially monogamous songbird
Authors: Forstmeier Wolfgang , Wang Daiping , Martin Katrin , Kempenaers Bart 
Published: May 2021

AbstractFemale mate choice is thought to be responsible for the evolution of many extravagant male ornaments and displays, but the costs of being too selective may hinder the evolution of choosiness. Selection against choosiness should be strongest in socially monogamous mating systems, because females may end up without a partner and forego reproduction, especially when many females prefer the same few partners (frequency-dependent selection). Here we quantify the fitness costs of having mating preferences that are difficult to satisfy. We capitalise on the recent discovery that female zebra finches (Taeniopygia guttata) prefer males of familiar song dialect. We measured female fitness in captive breeding colonies in which one third of females were given ample opportunity to choose a mate of their preferred dialect (two thirds of all males; ‘relaxed competition’), while two thirds of the females had to compete over a limited pool of mates they preferred (one third of all males; ‘high competition’). As expected, social pairings were strongly assortative with regard to song dialect. In the high-competition group, 26% of the females remained unpaired, yet they still obtained relatively high fitness by using brood parasitism as an alternative reproductive tactic. Another 31% of high-competition females paired disassortatively for song dialect. These females showed increased levels of extra-pair paternity, mostly with same-dialect males as sires, suggesting that preferences were not abolished after social pairing. However, females that paired disassortatively for song dialect did not have lower reproductive success. Overall, females in the high-competition group reached equal fitness as those that experienced relaxed competition. Our study suggests that alternative reproductive tactics such as egg dumping can help overcome the frequency-dependent costs of being highly selective in a monogamous mating system, thereby facilitating the evolution of female choosiness.
Evaluation of genotoxic and cytogenetic effects of saponins and aluminum hydroxide adjuvant on viral vaccine
Authors: Magnelli Roberta Fiusa , de Cássia Stocco Rita , da Silva Junior Pedro Ismael , Mendonça Ronaldo Zucatelli 
Published: May 2021

ABSTRACTBovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious disease characterized by the presence of benign tumors that can progress to malignancy. The phylogenetic classification of the PVs is performed based on the sequence homology of the Open Reading Frame L1, the most conserved among different viral serotypes. Given the immunogenicity of saponins, it,s has been used as a candidate as adjuvant use. For this reason, the safety of using saponin as an adjuvant has to be better determined to human or veterinary vaccine use. So, this study aimed to evaluate the mutagenic and genotoxic effect of saponins in comparison with the adjuvant widely used aluminum hydroxide using an isolated and purified L1 protein from BPV as model. In this study, genomic lesions, which after processed without repair can result in mutations, were detected by comet assay. Possible damages to genetic material caused by structural chromosomal changes (clastogenesis), as well as chromosomal losses (aneugenesis) were evaluated by the micronucleus test. Both tests were done on polychromatic erythrocytes and Vero cells. The evaluation of apoptosis and necrosis of treated Vero cells was made by Annexin V / PI staining and flow cytometry. The two vaccine products (L1 +Saponin and L1 + Aluminum Hydroxide) showed damages compatible with the positive control in the comet assay and both slightly elevated the micronucleus levels, in the Cell Viability Assay the results with Aluminum Hydroxide were satisfactory, characterizing Aluminum Hydroxide as a safer adjuvant according to the proposed tests, better than the saponins. Some fractions of the saponin extract separated by High Performance Liquid Chromatography were evaluated against genotoxic activity by comet assay, and their identities were confirmed by similarity to the reference standard by mass spectrometry.
Telomere-to-telomere genome assembly ofPhaeodactylum tricornutum
Authors: Giguere Daniel J. , Bahcheli Alexander T. , Slattery Samuel S. , Patel Rushali R. , Flatley Martin , Karas Bogumil J. , Edgell David R. , Gloor Gregory B. 
Published: May 2021

ABSTRACTPhaeodactylum tricornutumis a marine diatom with a growing genetic toolbox available and is being used in many synthetic biology applications. While most of the genome has been assembled, the currently available genome assembly is not a completed telomere-to-telomere assembly. Here, we used Oxford Nanopore long reads to build a telomere-to-telomere genome forPhaeodactylum tricornutum. We developed a graph-based approach to extract all unique telomeres, and used this information to manually correct assembly errors. In total, we found 25 nuclear chromosomes that comprise all previously assembled fragments, in addition to the chloroplast and mitochondrial genomes. We found that chromosome 19 has filtered long-read coverage and a quality estimate that suggests significantly less haplotype sequence variation than the other chromosomes. This work improves upon the previous genome assembly and provides new opportunities for genetic engineering of this species, including creating designer synthetic chromosomes.
The adenoviral E1B-55k protein present in HEK293 cells mediates abnormal accumulation of key WNT signaling proteins in large cytoplasmic aggregates
Authors: Olsen Petter Angell , Krauss Stefan 
Published: May 2021

ABSTRACTHEK293 cells are one of the most widely used cell lines in research and HEK293 cells are frequently used as anin vitromodel for studying the WNT signaling pathway. The HEK293 cell line was originally established by transfection of human embryonic kidney cells with sheared adenovirus 5 DNA and it is known that that HEK293 cells stably express the adenoviral E1A and E1B-55k proteins. Here we show that HEK293 cells display an unexpected distribution of key components of the WNT/β-catenin signaling pathway where AXIN1, APC, DVL2 and tankyrase are all co-localized in large spherical cytoplasmic aggregates. The cytoplasmic aggregates are enclosed by a narrow layer of the adenoviral E1B-55k protein. Reduction of E1B-55k protein levels leads to disappearance of the cytoplasmic aggregates thus corroborating an essential role of the E1B-55k protein in mediating the formation of the aggregates. Furthermore, HEK293 cells with reduced E1B-55k protein levels display reduced levels of transcriptional activation of WNT/β-catenin signaling upon stimulation by the Wnt3A agonist. The demonstrated influence of the E1B-55k protein on the cellular localization of WNT/β-catenin signaling components and on transcriptional regulation of WNT/β-catenin signaling asks for caution in the interpretation of data derived from the HEK293 cell line.
Systematic temporal analysis of peripheral blood transcriptomes usingTrendCatcheridentifies early and persistent neutrophil activation as a hallmark of severe COVID-19
Authors: Wang Xinge , Sanborn Mark , Dai Yang , Rehman Jalees 
Published: May 2021

AbstractStudying temporal gene expression shifts during disease progression provides important insights into the biological mechanisms that distinguish adaptive and maladaptive responses. Existing tools for the analysis of time course transcriptomic data are not designed to optimally identify distinct temporal patterns when analyzing dynamic differentially expressed genes (DDEGs). Moreover, there is a lack of methods to assess and visualize the temporal progression of biological pathways mapped from time course transcriptomic datasets. In this study, we developed an open-source R packageTrendCatcher(https://github.com/jaleesr/TrendCatcher), which applies the smoothing spline ANOVA model and break point searching strategy to identify and visualize distinct dynamic transcriptional gene signatures and biological processes from longitudinal datasets. We usedTrendCatcherto perform a systematic temporal analysis of COVID-19 peripheral blood transcriptomes, including bulk RNA-seq and scRNA-seq time course data.TrendCatcheruncovered the early and persistent activation of neutrophils and coagulation pathways as well as impaired type I interferon (IFN-I) signaling in circulating cells as a hallmark of patients who progressed to severe COVID-19, whereas no such patterns were identified in individuals receiving SARS- CoV-2 vaccinations or patients with mild COVID-19. These results underscore the importance of systematic temporal analysis to identify early biomarkers and possible pathogenic therapeutic targets.
Multivalent interactions make adherens junction-cytoskeletal linkage robust during morphogenesis
Authors: Perez-Vale Kia Z. , Yow Kristi D. , Byrnes Amy E. , Finegan Tara M. , Slep Kevin C. , Peifer Mark 
Published: May 2021

AbstractEmbryogenesis requires cells to change shape and move without disrupting epithelial integrity. This requires robust, responsive linkage between adherens junctions and the actomyosin cytoskeleton. UsingDrosophilamorphogenesis we define molecular mechanisms mediating junction-cytoskeletal linkage and explore the role of mechanosensing. We focus on the junction-cytoskeletal linker Canoe, a multidomain protein. We engineered thecanoelocus to define how its domains mediate its mechanism of action. To our surprise, the PDZ and FAB domains, which we thought connected junctions and F-actin, are not required for viability or mechanosensitive recruitment to junctions under tension. The FAB domain stabilizes junctions experiencing elevated force, but in its absence most cells recover, suggesting redundant interactions. In contrast, the Rap1-binding RA domains are critical for all Cno functions and for enrichment at junctions under tension. This supports a model in which junctional robustness derives from a large protein network assembled via multivalent interactions, with proteins at network nodes and some node connections more critical than others.
Single gene initiates evolution of epithelial architecture and function
Authors: Noeske Viola , Caglayan Emre , Lemke Steffen 
Published: May 2021

AbstractEpithelial monolayers are a hallmark of the architecture of metazoan tissues: they provide stability, serve as barriers, and fold into organs. Epithelial cells vary in shape, ranging from flat and spread out to tall and slim. Dynamic epithelial shape changes have been explored in the context of tissue folding, where local cytoskeletal modulations cause epithelial bending and folding. Comparatively little is known about how entire tissues are transformed from a short to tall architecture. Here we show that shape regulation in epithelia can be governed by the activity of a single gene. We use a comparative approach in distantly related flies to experimentally decode the developmental program that directs the formation of columnar epithelia in the blastoderm and thus determines the physiological features of the resulting epithelium. We uncover an evolutionary novel, membrane-associated protein that emerged in flies and triggered a new development program, the cuboidal-to-columnar transformation of epithelial tissues. slow-as-molasses (slam) encodes a Dia/F-actin regulator that exploits an intrinsic morphological plasticity of cells to transform tissues. Our findings demonstrate that a single, newly emerged factor that amplifies its activity in epithelia provides the basis for adaptation and initiates the evolution of novel developmental programs.
Wikidata and the bibliography of life
Authors: Page Roderic D. M. 
Published: May 2021

AbstractBiological taxonomy rests on a long tail of publications spanning nearly three centuries. Not only is this literature vital to resolving disputes about taxonomy and nomenclature, for many species it represents a key source - indeed sometimes the only source - of information about that species. Unlike other disciplines such as biomedicine, the taxonomic community lacks a centralised, curated literature database (the “bibliography of life”). This paper argues that Wikidata can be that database as it has flexible and sophisticated models of bibliographic information, and an active community of people and programs (“bots”) adding, editing, and curating that information. The paper also describes a tool to visualise and explore bibliography information in Wikidata and how it links to both taxa and taxonomists.
Explainable Sleep Stage Classification with Multimodal Electrophysiology Time-series
Authors: Ellis Charles A. , Zhang Rongen , Carbajal Darwin A. , Miller Robyn L. , Calhoun Vince D. , Wang May D. 
Published: May 2021

AbstractMany automated sleep staging studies have used deep learning approaches, and a growing number have used multimodal data to improve their classification performance. However, few studies using multimodal data have provided model explainability. Some have used traditional ablation approaches that “zero out” a modality. However, the samples that result from this ablation are unlikely to be found in real electroencephalography (EEG) data, which could adversely affect the importance estimates that result. Here, we train a convolutional neural network for sleep stage classification with EEG, electrooculograms (EOG), and electromyograms (EMG) and propose an ablation approach that replaces each modality with values that approximate the line-related noise commonly found in electrophysiology data. The relative importance that we identify for each modality is consistent with sleep staging guidelines, with EEG being important for most sleep stages and EOG being important for Rapid Eye Movement (REM) and nonREM stages. EMG showed low relative importance across classes. A comparison of our approach with a “zero out” ablation approach indicates that while the importance results are consistent for the most part, our method accentuates the importance of modalities to the model for the classification of some stages like REM (p < 0.05). These results suggest that a careful, domain-specific selection of an ablation approach may provide a clearer indicator of modality importance. Further, this study provides guidance for future research on using explainability methods with multimodal electrophysiology data.
Metamodal Coupling of Vibrotactile and Auditory Speech Processing Systems Through Matched Stimulus Representations
Authors: Damera Srikanth R. , Malone Patrick S. , Stevens Benson W. , Klein Richard , Eberhardt Silvio P. , Auer Edward T. , Bernstein Lynne E. , Riesenhuber Maximilian 
Published: May 2021

SummaryIt has been postulated that the brain is organized by “metamodal”, sensory-independent cortical modules implementing particular computations, leading to the intriguing hypothesis that brain areas can perform tasks (such as word recognition) not just in “standard” sensory modalities but also in novel sensory modalities. Yet, evidence for this theory, especially in neurotypical subjects, has been variable. We hypothesized that effective metamodal engagement of a brain area requires congruence between the novel and standard sensory modalities not only at the task level (e.g., “word recognition”) but critically also a match at the algorithmic level (in Marr’s terminology), i.e., at the level of neural representation of the information of interest. To test this hypothesis, we trained participants to recognize vibrotactile versions of auditory words using two encoding schemes. The vocoded approach preserved the dynamics and representational similarities of auditory speech while the token-based approach used an abstract phoneme-based code. Although both groups learned the vibrotactile word recognition task, only in the vocoded group did trained vibrotactile stimuli recruit the auditory speech network and lead to increased coupling between somatosensory and auditory speech areas. In contrast, the token-based encoding appeared to rely on paired-associate learning. Thus, matching neural input representations is a critical factor for assessing and leveraging the metamodal potential of cortical modules.
SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination
Authors: Hoffmann Markus , Hofmann-Winkler Heike , Krüger Nadine , Kempf Amy , Nehlmeier Inga , Graichen Luise , Sidarovich Anzhalika , Moldenhauer Anna-Sophie , Winkler Martin S. , Schulz Sebastian , Jäck Hans-Martin , Stankov Metodi V. , Behrens Georg M. N. , Pöhlmann Stefan 
Published: May 2021

SUMMARYThe emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic. The number of COVID-19 cases and deaths in India has risen steeply in recent weeks and a novel SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein of B.1.617 harbors two mutations in the receptor binding domain, which interacts with the ACE2 receptor and constitutes the main target of neutralizing antibodies. Therefore, we analyzed whether B.1.617 is more adept in entering cells and/or evades antibody responses. B.1.617 entered two out of eight cell lines tested with slightly increased efficiency and was blocked by entry inhibitors. In contrast, B.1.617 was resistant against Bamlanivimab, an antibody used for COVID-19 treatment. Finally, B.1.617 evaded antibodies induced by infection or vaccination, although with moderate efficiency. Collectively, our study reveals that antibody evasion of B.1.617 may contribute to the rapid spread of this variant.