bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust genetic analysis of the X-linked anophthalmic (Ie) mouse
Authors: Hernandez-Moran Brianda Areli , Papanastasiou Andrew S , Parry Dave , Meynert Alison , Gautier Phillipe , Grimes Graeme , Adams Ian R , Trejo-Reveles Violeta , Bengani Hemant , Keighren Margaret , Jackson Ian J , Adams David J , FitzPatrick David R , Rainger Joe 
Published: August 2022

AbstractAnophthalmia (missing eye) describes a failure of early embryonic ocular development. Mutations in a relatively small set of genes account for 75% of bilateral anophthalmia cases, yet 25% of families currently are left without a molecular diagnosis. Here we report our experimental work that aimed to uncover the developmental and genetic basis of the anophthalmia characterising the X-linked Ie (eye-ear reduction) X-ray induced allele in mouse that was first identified in 1947. Histological analysis of the embryonic phenotype showed failure of normal eye development after the optic vesicle stage with particularly severe malformation of the ventral retina. Linkage analysis mapped this mutation to a ∼ 6Mb region on the X chromosome. Short and long read whole-genome sequencing (WGS) of affected and unaffected male littermates confirmed the Ie linkage but identified no plausible causative variants or structural rearrangements. These analyses did reduce the critical candidate interval and revealed evidence of multiple variants within the ancestral DNA, although none were found that altered coding sequences or that were unique to Ie. To investigate early embryonic events at a genetic level, we then generated mouse ES cells derived from male Ie embryos and wild type littermates. RNA-seq and accessible chromatin sequencing (ATAC-seq) data generated from cultured optic vesicle organoids did not reveal any large differences in gene expression or accessibility of putative cis-regulatory elements between Ie and wild type. However, an unbiased TF-footprinting analysis of accessible chromatin regions did provide evidence of a genome-wide reduction in binding of transcription factors associated with ventral eye development in Ie, and evidence of an increase in binding of the Zic-family of transcription factors, including Zic3, which is located within the Ie-refined critical interval. We conclude that the refined Ie critical region at chrX: 56,145,000-58,385,000 contains multiple genetic variants that may be linked to altered cis regulation but does not contain a convincing causative mutation. Changes in the binding of key transcription factors to chromatin causing altered gene expression during development, possibly through a subtle mis-regulation of Zic3, presents a plausible cause for the anophthalmia phenotype observed in Ie, but further work is required to determine the precise causative allele and its genetic mechanism.
Transfer learning identifies sequence determinants of regulatory element accessibility
Authors: Salvatore Marco , Horlacher Marc , Marsico Annalisa , Winther Ole , Andersson Robin 
Published: August 2022

AbstractDysfunction of regulatory elements through genetic variants is a central mechanism in the pathogenesis of disease. To better understand disease etiology, there is consequently a need to understand how DNA encodes regulatory activity. Deep learning methods show great promise for modeling of biomolecular data from DNA sequence but are limited to large input data for training. Here, we develop ChromTransfer, a transfer learning method that uses a pre-trained, cell-type agnostic model of open chromatin regions as a basis for fine-tuning on regulatory sequences. We demonstrate superior performances with ChromTransfer for learning cell-type specific chromatin accessibility from sequence compared to models not informed by a pre-trained model. Importantly, ChromTransfer enables fine-tuning on small input data with minimal decrease in accuracy. We show that ChromTransfer uses sequence features matching binding site sequences of key transcription factors for prediction. Together, these results demonstrate ChromTransfer as a promising tool for learning the regulatory code.
Naturalistic language comprehension is supported by alpha and beta oscillations linked to domain-general inhibition and reactivation
Authors: Zioga Ioanna , Weissbart Hugo , Lewis Ashley G. , Haegens Saskia , Martin Andrea E. 
Published: August 2022

AbstractBrain oscillations are prevalent in all species and are involved in numerous perceptual operations. Alpha oscillations are thought to facilitate processing through the inhibition of task-irrelevant networks, while beta oscillations are linked to the reactivation of content representations. Can the proposed functional role of alpha and beta oscillations be generalized from low-level operations to higher-level cognitive processes? Here we address this question focusing on naturalistic spoken language processing. Twenty-two (18 female) Dutch native speakers listened to stories in spoken Dutch and French while magnetoencephalography (MEG) was recorded. We used dependency parsing to identify three dependency states at each word, as the number of (1) newly opened dependencies, (2) dependencies that remained open, and (3) resolved dependencies. We then constructed linear forward models to predict alpha and beta power from the dependency features. Results showed that dependency features predict alpha and beta power in language-related regions beyond low-level linguistic features. Left temporal, fundamental language regions are involved in language comprehension in the alpha band, while frontal and parietal, higher-order language regions, and motor regions are mostly involved in the beta band. Critically, alpha and beta band dynamics seem to subserve language comprehension tapping into syntactic structure building and semantic composition by providing low-level mechanistic operations for inhibition and reactivation processes. Overall, this study sheds light on the role of alpha and beta oscillations during naturalistic language processing, providing evidence for the generalizability of these dynamics from perceptual to complex linguistic processes.Significance StatementPrior research identified the functional role of alpha and beta oscillations in basic perceptual and motor functions. However, it remains unclear whether their proposed role can be generalized to higher-level processes during language comprehension. Here, we found that high-level syntactic features predict alpha and beta power in language-related regions beyond low-level linguistic features when listening to comprehensible naturalistic speech. Our work contributes to the debate about whether the functional roles of brain oscillations are domain-general or depend on the task at hand. We offer experimental findings that integrate a neuroscientific framework on the role of brain oscillations as “building blocks” with language comprehension as a compositional process, and novel evidence regarding the encoding of higher-level syntactic operations in the brain. This supports the view of a domain-general role of cortical oscillations across the hierarchy of cognitive functions, from low-level sensory operations to complex linguistic processes.
Genomic local adaptation of a generalist plant species to pollinator communities and abiotic factors
Authors: Frachon L. , Arrigo L. , Rusman Q. , Poveda L. , Qi W. , Scopece G. , Schiestl F.P. 
Published: August 2022

AbstractThe reproductive success of generalist flowering plants is influenced by a complex ecological network that includes interactions with a diverse pollinator community and abiotic factors. However, knowledge about of the adaptative potential of plants to complex ecological networks and the underlying genetic mechanisms is still limited. Based on a pool-sequencing approach of 21 natural populations of Brassica incana in Southern Italy, we combined a genome-environmental association analysis with a genome scan for signature of selection to discover genetic variants associated with ecological variation. We demonstrated that B. incana is locally adapted both to the identity of functional categories and overall pollinator interactions. Interestingly, we observed only few shared candidate genes associated with long-tongue bees, soil texture, and temperature variation. Our results highlight the genomic architecture of generalist flowering plant adaptation to complex biotic interactions, and the importance of considering multiple environmental factors to describe the adaptive landscape of plant populations.
SARS-CoV-2 entry route impacts a range of downstream viral and cellular processes
Authors: Qu Bingqian , Miskey Csaba , Gömer André , Potmus Dylan , Nocke Maximillian , Kleinert Robin D.V. , Itotia Tabitha K. , Valder Lara , Brückmann Janice , Höck Sebastian , Hastert Florian D. , von Rhein Christine , Schürmann Christoph , Ebenig Aileen , Widera Marek , Ciesek Sandra , Pfaender Stephanie , Ivics Zoltán , Schnierle Barbara S. , Tarr Alexander W. , Goffinet Christine , Mühlebach Michael D. , Todt Daniel , Brown Richard J.P. 
Published: August 2022

AbstractSARS-CoV-2 entry is promoted by both cell-surface TMPRSS2 and endolysosomal cathepsins. To investigate the impact of differentially routed virions on host and viral processes, lung epithelial cells expressing distinct combinations of entry factors were infected with authentic viruses. Entry route determined early rates of viral replication and transcription, egress and inhibitor sensitivity, with differences observed between virus strains. Transcriptional profiling revealed that induction of innate immunity was correlated to viral genome and transcript abundance in infected cells. Surface entry triggered early activation of antiviral responses, reducing cumulative virion production, while endolysosomal entry delayed antiviral responses and prolonged virus shedding due to extended cell viability. The likely molecular footprints of escape from antiviral effector targeting were also recorded in viral genomes and correlated with entry route-dependent immune status of cells. TMPRSS2 orthologues from diverse mammals, but not zebra fish, facilitated infection enhancement, which was more pronounced for ancestral strains. Leveraging RNA-seq and scRNA-seq datasets from SARS-CoV-2 infected hamsters, we validate aspects of our model in vivo. In summary, we demonstrate that distinct cellular and viral processes are linked to viral entry route, collectively modulating virus shedding, cell-death rates and viral genome evolution.
Dynamics of hinged wings in strong upward gusts
Authors: Stevenson Jonathan P. J. , Cheney Jorn A. , Usherwood James R. , Bomphrey Richard J. , Windsor Shane P. 
Published: August 2022

AbstractA bird’s wings are articulated to its body via highly mobile shoulder joints. The wings possess an impressive range of motion, which allows for movements that can modulate the production of aerodynamic load in flight. This is crucial for stability and control—particularly in gusty or turbulent environments. In this study, we develop a dynamics model to examine how a bird-scale gliding aircraft can use wing-root hinges (analogous to avian shoulder joints) to reject the initial impact of a strong upward gust. Our idea requires that the spanwise centre of pressure and the centre of percussion of the hinging wing start, and stay, in good initial alignment (the centre of percussion here is related to the idea of a ‘sweet spot’ on a bat, as in cricket or baseball). We propose a method for achieving this rejection passively, for which the essential ingredients are: (i) well-considered lift and mass distributions; (ii) constant-torque hinges; and (iii) a wing whose sections stall softly. When configured correctly, the gusted wings will first pivot on their hinges without disturbing the fuselage of the aircraft, affording time for other corrective actions to engage. We expect this system to enhance the control of aircraft that fly in gusty conditions.
Multiscale Analysis of Pangenome Enables Improved Representation of Genomic Diversity For Repetitive And Clinically Relevant Genes
Authors: Chin Chen-Shan , Behera Sairam , Khalak Asif , Sedlazeck Fritz J , Wagner Justin , Zook Justin M. 
Published: August 2022

AbstractThe advancements in sequencing technologies and assembly methods enable the regular production of high-quality genome assemblies characterizing complex regions. However, challenges remain in efficiently interpreting variations at various scales, from smaller tandem repeats to megabase re-arrangements, across many human genomes. We present a pangenome research toolkit enabling analyses of complex pangenome variations at multiple scales. A graph decomposition method is developed for interpreting such variations. Surveying a set of 395 challenging and medically important genes in pangenome provides quantitative insights into repetitiveness and diversity that could impact the accuracy of variant calls. We apply the graph decomposition methods to the Y-chromosome gene, DAZ1/DAZ2/DAZ3/DAZ4, of which structural variants have been linked to male infertility, and X-chromosome genes OPN1LW and OPN1MW linked to eye disorders, highlighting the power of PGR-TK and pangenomics to resolve complex variation in regions of the genome that were previously too complex to analyze across many haplotypes.
Phanta: Phage-inclusive profiling of human gut metagenomes
Authors: Pinto Yishay , Chakraborty Meenakshi , Jain Navami , Bhatt Ami S 
Published: August 2022

AbstractThe human gut microbiome is a diverse ecosystem that encompasses multiple domains of life and plays a vital role in human health. Due to technical limitations, most microbiome studies have focused on gut prokaryotes, overlooking bacteriophages and other gut viruses. The most common method to profile viruses is to assemble shotgun metagenomic reads - often from virus-enriched samples - and identify viral genomes de novo. While valuable, this resource-intensive and reference-independent method has limited sensitivity. To overcome these drawbacks, we developed Phanta, which profiles human gut metagenomes in a virus-inclusive manner directly from short reads utilizing recently published catalogs of gut viral genomes. Phanta incorporates k-mer based classification tools and was developed with virus-specific properties in mind. Specifically, it includes optimizations considering viruses’ small genome size, sequence homology with prokaryotes, and interactions with other members of the gut microbial community. Based on simulations, the workflow is fast and accurate with respect to both prokaryotes and viruses, minimizing false positive species identification using a novel genome coverage-based strategy. When applied to metagenomes from healthy adults, Phanta identified ~200 viral species per sample, ~5x more than the standard assembly-based methods. Notably, we observed a 2:1 ratio between gut viruses and bacteria, with higher interindividual variability of the gut virome compared to the gut bacteriome. Phanta performs equally well on bulk vs. virus-enriched metagenomes, making it possible to study prokaryotes and viruses in a single experiment, with a single analysis. Phanta can tandemly profile gut viruses and prokaryotes in existing and novel datasets, and can therefore identify cross-domain interactions with likely relevance to human health. We expect that Phanta will reduce the barrier to virus-inclusive studies of the human gut microbiome, thus making it standard practice.
Alveolar Repair Following Lipopolysaccharide-induced Injury Requires Cell-Extracellular Matrix Interactions
Authors: Sucre Jennifer M.S. , Bock Fabian , Negretti Nicholas M. , Benjamin John T. , Gulleman Peter M. , Dong Xinyu , Ferguson Kimberly T. , Jetter Christopher S. , Han Wei , Liu Yang , Kook Seunghyi , Gokey Jason J. , Guttentag Susan H. , Kropski Jonathan A. , Blackwell Timothy S. , Zent Roy , Plosa Erin J. 
Published: August 2022

AbstractDuring alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat type 1 alveolar epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if β1-containing integrins are required during repair following acute injury, we administeredE. colilipopolysaccharide (LPS) by intratracheal injection to mice with a post-developmental deletion of β1 integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, β1-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells co-expressing type 2, type 1, and mixed intermediate cell state markers, with few mature type 1 cells. β1-deficient AT2 cells showed persistently increased proliferation after injury, which was blocked by inhibiting NF-κB activation in these cells. Lineage tracing experiments revealed that β1-deficient AT2 cells failed to differentiate into mature type 1 alveolar epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires β1-containing integrins.
Severity Predictors of COVID-19 in SARS-CoV-2 Variant, Delta and Omicron Period; Single Center Study
Authors: Ogawa Fumihiro , Oi Yasufumi , Honzawa Hiroshi , Misawa Naho , Takeda Tomoaki , Kikuchi Yuusuke , Fukui Ryosuke , Tanaka Katsushi , Kano Daiki , Kato Hideaki , Abe Takeru , Takeuchi Ichiro 
Published: August 2022

AbstractBackgroundThe outcomes of coronavirus disease 2019 (COVID-19) treatment have improved due to vaccination and the establishment of better treatment regimens. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, and the corresponding changes in the characteristics of the disease present new challenges in patient management. This study aimed to analyze predictors of COVID-19 severity caused by the delta and omicron variants of SARS-CoV-2.MethodsWe retrospectively analyzed the data of patients who were admitted for COVID-19 at Yokohama City University Hospital from August 2021 to March 2022.ResultsA total of 141 patients were included in this study. Of these, 91 had moderate COVID-19, whereas 50 had severe COVID-19. There were significant differences in sex, vaccination status, dyspnea, sore throat symptoms, and body mass index (BMI) (p <0.0001, p <0.001, p <0.001, p=0.02, p< 0.0001, respectively) between the moderate and severe COVID-19 groups. Regarding comorbidities, smoking habit and renal dysfunction were significantly different between the two groups (p=0.007 and p=0.01, respectively). Regarding laboratory data, only LDH level on the first day of hospitalization was significantly different between the two groups (p<0.001). Multiple logistic regression analysis revealed that time from the onset of COVID-19 to hospitalization, BMI, smoking habit, and LDH level were significantly different between the two groups (p<0.03, p=0.039, p=0.008, p<0.001, respectively). The cut-off value for the time from onset of COVID-19 to hospitalization was four days (sensitivity, 0.73; specificity, 0.70).ConclusionsTime from the onset of COVID-19 to hospitalization is the most important factor in the prevention of the aggravation of COVID-19 caused by the delta and omicron SARS-CoV-2 variants. Appropriate medical management within four days after the onset of COVID-19 is essential for preventing the progression of COVID-19, especially in patients with smoking habits.
Alcanivorax borkumensisBiofilms Enhance Oil Degradation By Interfacial Tubulation
Authors: Prasad M. , Obana N. , Lin S.-Z. , Sakai K. , Blanch-Mercader C. , Prost J. , Nomura N. , Rupprecht J.-F. , Fattaccioli J. , Utada A. S. 
Published: August 2022

ABSTRACTAlcanivorax borkumensisare prominent actors in oil spill bioremediation; however, the interfacial dynamics of their biofilms and its role in oil degradation remain unclear. Longitudinal tracking of biofilm-covered oil microdroplets using microfluidics reveals a spontaneous morphological transition from a thick biofilm phenotype to a thin dendritic phenotype optimized for high oil consumption rates. We show experimentally that biofilm dendrites emerge from aster-like nematic defects in the thin biofilms. We develop a theoretical model that elucidates the transition between phenotypes, linking tubulation to decreased interfacial tension and increased cell hydrophobicity, which we verify experimentally. We demonstrate positional control over the nematic defects on the droplets using microfluidics, causing the biofilm to dimple the droplets. Our results reveal howA. borkumensisbiofilms utilize topological defects to increase oil access to achieve superior oil consumption rates, which may be a general strategy in oil-consuming bacteria.ONE SENTENCE SUMMARYA. borkumensisadapt their interfacial properties over time to evolve their biofilm phenotype and increase their oil consumption
Beyond variance: simple random distributions are not a good proxy for intraspecific variability in systems with environmental structure
Authors: Girard-Tercieux Camille , Vieilledent Ghislain , Clark Adam , Clark James S. , Courbaud Benoit , Fortunel Claire , Kunstler Georges , Pélissier Raphaël , Rüger Nadja , Maréchaux Isabelle 
Published: August 2022

AbstractThe role of intraspecific variability (IV) in shaping community dynamics and species coexistence has been intensively discussed over the past decade and modelling studies have played an important role in that respect. However, these studies often implicitly assume that IV can be represented by independent random draws around speciesspecific mean parameters. This major assumption has largely remained undiscussed, although a great part of observed IV is structured in space or time, in particular when environmental dimensions that influence individual performance are imperfectly characterised or unobserved in the field. To test the impact of this strong assumption on the outcome of community dynamics models, we designed a simulation experiment where we varied the level of knowledge of the environment in virtual communities, resulting in different relative importance of explainedvsunexplained spatial individual variation in performance. We used a community dynamics simulator to generate communities where the unexplained individual variation is, or is not, added as an unstructured random noise. Communities simulated with unstructured IV never reached the community diversity and composition of those where all the variation was explained and structured (perfect knowledge model). This highlights that incorporating unstructured IV (i.e. a random noise) to account for unexplained (but structured) variation can lead to incorrect simulations of community dynamics. In addition, the effects of unstructured IV on community diversity and composition depended on the relative importance of structuredvsunstructured IV,i.e. on the level of knowledge of the environment, which may partly explain the contrasting results of previous studies on the effect of IV on species coexistence. In particular, the effect of unstructured IV on community diversity was positive when the proportion of structured IVvsunstructured IV in the model was low, but negative when this proportion was high. This is because unstructured random noise can either limit the competitive exclusion of inferior competitors in low dimensions or destabilise tight niche partitioning in high dimension. Our study suggests that it is crucial to account for the sources and structure of observed IV in real communities to better understand its effect on community assembly and properly include it in community dynamics models.