bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifunctional optrode for opsin delivery, optical stimulation, and electrophysiological recordings in freely moving rats
Authors: Sharma Kirti , Jaeckel Zoe , Schneider Artur , Paul Oliver , Diester Ilka , Ruther Patrick 
Published: May 2021

AbstractObjectiveOptogenetics involves delivery of light-sensitive opsins to the target brain region, as well as introduction of optical and electrical devices to manipulate and record neural activity, respectively, from the targeted neural population. Combining these functionalities in a single implantable device is of great importance for a precise investigation of neural networks while minimizing tissue damage.ApproachWe report on the development, characterization, and in vivo validation of a multifunctional optrode that combines a silicon-based neural probe with an integrated microfluidic channel, and an optical glass fiber in a compact assembly. The silicon probe comprises an 11-μm-wide fluidic channel and 32 recording electrodes (diameter 30 μm) on a tapered probe shank with a length, thickness, and maximum width of 7.5 mm, 50 μm, and 150 μm, respectively. The size and position of fluidic channels, electrodes, and optical fiber can be precisely tuned according to the in vivo application.Main resultsWith a total system weight of 0.97 g, our multifunctional optrode is suitable for chronic in vivo experiments requiring simultaneous drug delivery, optical stimulation, and neural recording. We demonstrate the utility of our device in optogenetics by injecting a viral vector carrying a ChR2-construct in the prefrontal cortex and subsequent photostimulation of the transfected neurons while recording neural activity from both the target and adjacent regions in a freely moving rat. Additionally, we demonstrate a pharmacological application of our device by injecting GABA antagonist bicuculline in an anesthetized rat brain and simultaneously recording the electrophysiological response.SignificanceOur triple-modality device enables a single-step optogenetic surgery. In comparison to conventional multi-step surgeries, our approach achieves higher spatial specificity while minimizing tissue damage.Graphical abstract
Natural tolerance to transposition is associated with double-strand break repair and germ-cell differentiation
Authors: Lama Jyoti , Srivastav Satyam , Tasnim Sadia , Hubbard Donald , Hadjipanteli Savana , Kelleher Erin S. 
Published: May 2021

AbstractTransposable elements (TE) are mobile genetic parasites whose unregulated activity in the germline causes DNA damage and sterility. While the regulation of TE mobilization by hosts is studied extensively, little is known about mechanisms that could allow germline cells to persist in the face of genotoxic stress imposed by active transposition. Such tolerance mechanisms are predicted to be beneficial when new TEs invade and host repression has not yet evolved. Here we use hybrid dysgenesis—a sterility syndrome ofDrosophilacaused by transposition of invading DNA transposons—to uncover genetic variants that confer tolerance to transposition. Using a panel of highly recombinant inbred lines ofDrosophila melanogaster, we identified two linked quantitative trait loci (QTL), that determine tolerance in young and old females, respectively. Through transcriptomic and phenotypic comparisons, we provide evidence that young tolerant females exhibit enhanced repair of double-stranded breaks, explaining their ability to withstand high germline transposition rates. We furthermore identify the germline differentiation factorbratas an independent tolerance factor, whose activity may promote germline maintenance in aging dysgenic females. Together, our work reveals the diversity of potential tolerance mechanisms across development, as well as tolerant variants that may be beneficial in the context ofP-element transposition.
Signatures of copy number alterations in human cancer
Authors: Steele Christopher D. , Abbasi Ammal , Islam S. M. Ashiqul , Khandekar Azhar , Haase Kerstin , Hames Shadi , Tarabichi Maxime , Lesluyes Tom , Flanagan Adrienne M. , Mertens Fredrik , Van Loo Peter , Alexandrov Ludmil B. , Pillay Nischalan 
Published: May 2021

ABSTRACTThe gains and losses of DNA that emerge as a consequence of mitotic errors and chromosomal instability are prevalent in cancer. These copy number alterations contribute to cancer initiaition, progression and therapeutic resistance. Here, we present a conceptual framework for examining the patterns of copy number alterations in human cancer using whole-genome sequencing, whole-exome sequencing, and SNP6 microarray data making it widely applicable to diverse datasets. Deploying this framework to 9,873 cancers representing 33 human cancer types from the TCGA project revealed a set of 19 copy number signatures that explain the copy number patterns of 93% of TCGA samples. 15 copy number signatures were attributed to biological processes of whole-genome doubling, aneuploidy, loss of heterozygosity, homologous recombination deficiency, and chromothripsis. The aetiology of four copy number signatures are unexplained and some cancer types have unique patterns of amplicon signatures associated with extrachromosomal DNA, disease-specific survival, and gains of proto-oncogenes such asMDM2. In contrast to base-scale mutational signatures, no copy number signature associated with known cancer risk factors. The results provide a foundation for exploring patterns of copy number changes in cancer genomes and synthesise the global landscape of copy number alterations in human cancer by revealing a diversity of mutational processes giving rise to copy number changes.
Maternal Piwi Regulates Primordial Germ Cell Development to Ensure the Fertility of Female Progeny inDrosophila
Authors: Gonzalez Lauren E , Tang Xiongzhuo , Lin Haifan 
Published: May 2021

ABSTRACTIn many animals, germline development is initiated by proteins and RNAs that are expressed maternally. PIWI proteins and their associated small noncodingPIWI-interacting RNAs (piRNAs), which guide PIWI to target RNAs by base-pairing, are among the maternal components deposited into the germline of the early embryo inDrosophila. Piwi has been extensively studied in the adult ovary and testis, where it is required for transposon suppression, germline stem cell self-renewal, and fertility. Consequently, loss of Piwi in the adult ovary usingpiwi-null alleles or knockdown from early oogenesis results in complete sterility, limiting investigation into possible embryonic functions of maternal Piwi. In this study, we show that the maternal Piwi protein persists in the embryonic germline through gonad coalescence, suggesting that maternal Piwi can regulate germline development beyond early embryogenesis. Using a maternal knockdown strategy, we find that maternal Piwi is required for the fertility and normal gonad morphology of female, but not male, progeny. Following maternalpiwiknockdown, transposons were mildly derepressed in the early embryo but were fully repressed in the ovaries of adult progeny. Furthermore, the maternal piRNA pool was diminished, reducing the capacity of the PIWI/piRNA complex to target zygotic genes during embryogenesis. Examination of embryonic germ cell proliferation and ovarian gene expression showed that the germline of female progeny was partially masculinized by maternalpiwiknockdown. Our study reveals a novel role for maternal Piwi in the germline development of female progeny and suggests that the PIWI/piRNA pathway is involved in germline sex determination inDrosophila.
Single-molecule imaging of microRNA-mediated gene silencing in cells
Authors: Kobayashi Hotaka , Singer Robert H. 
Published: May 2021

AbstractMicroRNAs (miRNAs) are small non-coding RNAs, which regulate the expression of thousands of genes; miRNAs silence gene expression from complementary mRNAs through translational repression and mRNA decay. For decades, the function of miRNAs has been studied primarily by ensemble methods, where a bulk collection of molecules is measured outside cells. Thus, the behavior of individual molecules during miRNA-mediated gene silencing, as well as their spatiotemporal regulation inside cells, remains mostly unknown. Here we report single-molecule methods to visualize each step of miRNA-mediated gene silencingin situinside cells. Simultaneous visualization of single mRNAs, translation, and miRNA-binding revealed that miRNAs preferentially bind to translated mRNAs rather than untranslated mRNAs. Spatiotemporal analysis based on our methods uncovered that miRNAs bind to mRNAs immediately after nuclear export. Subsequently, miRNAs induced translational repression and mRNA decay within 30 and 60 min, respectively, after the binding to mRNAs. This methodology provides a framework for studying mRNA regulation at the single-molecule level with spatiotemporal information inside cells.
AutoGGN: A Gene Graph Network AutoML Tool for Multi-Omics Research
Authors: Zhang Lei , Li Ping , Shen Wen , Xu Chi , Liu Denghui , He Wenjun , Xu Zhimeng , Zhang Chenyi , Qiao Nan 
Published: May 2021

AbstractOmics data identifies biological characteristics from genetic to phenotypic levels during the life span. Molecular interaction networks have a fundamental impact on life activities. Integrating omics data and molecular interaction networks will help researchers delve into comprehensive information underlying the data. Here, we proposed a new multimodal method called AutoGGN to aggregate multi-omics data and molecular interaction networks based on graph convolutional neural networks. We evaluated AutoGGN using two different tasks: cancer type classification and single-cell stage classification. On both tasks, AutoGGN showed better performance compared to other methods, the trend is relevant to the ability of utilizing much more information from biological data. The phenomenon indicated AutoGGN has the potential to incorporate valuable information from molecular interaction networks and multi-omics data effectively. Furthermore, in order to provide a better understanding of the mechanism of prediction results, we assessed the explanation using SHAP module and identified the key genes contributing to the prediction of classification, which will provide insights for the downstream design of biological experiments.
Metagenomic investigation of the equine faecal microbiome reveals extensive taxonomic and functional diversity
Authors: Gilroy Rachel , Leng Joy , Ravi Anuradha , Adriaenssens Evelien M. , Oren Aharon , Baker David , La Ragione Roberto M. , Proudman Christopher , Pallen Mark J. 
Published: May 2021

AbstractBackgroundThe horse plays crucial roles across the globe, including in horseracing, as a working and companion animal and as a food animal. The horse hindgut microbiome makes a key contribution in turning a high fiber diet into body mass and horsepower. However, despite its importance, the horse hindgut microbiome remains largely undefined. Here, we applied culture-independent shotgun metagenomics to thoroughbred equine faecal samples to deliver novel insights into this complex microbial community.ResultsWe performed metagenomic sequencing on five equine faecal samples to construct 123 high- or medium-quality metagenome-assembled genomes from Bacteria and Archaea. In addition, we recovered nearly 200 bacteriophage genomes. We document surprising taxonomic and functional diversity, encompassing dozens of novel or unnamed bacterial genera and species, to which we have assigned newCandidatusnames. Many of these genera are conserved across a range of mammalian gut microbiomes.ConclusionsOur metagenomic analyses provide new insights into the bacterial, archaeal and bacteriophage components of the horse gut microbiome. The resulting datasets provide a key resource for future high-resolution taxonomic and functional studies on the equine gut microbiome.
Diverse mechanisms for epigenetic imprinting in mammals
Authors: Andergassen Daniel , Smith Zachary D. , Rinn John L. , Meissner Alexander 
Published: May 2021

SUMMARYGenomic imprinting and X chromosome inactivation (XCI) require epigenetic mechanisms to direct allele-specific expression. Despite their critical roles in embryonic development, how universal epigenetic regulators coordinate these specific tasks from single locus to chromosome-scale remains understudied. Here, we systematically disrupted multiple essential epigenetic pathways within polymorphic F1 zygotes to examine postimplantation effects on canonical and non-canonical genomic imprinting as well as X chromosome inactivation. We find that DNA methylation and Polycomb group repressors are both indispensable for autosomal imprinting, albeit at distinct gene sets. Moreover, the extraembryonic ectoderm relies on a broader spectrum of unique imprinting mechanisms, including non-canonical targeting of maternal endogenous retrovirus (ERV) driven promoters by G9a. We further utilize our data to identify Polycomb dependent and independent gene clusters on the imprinted X chromosome, which appears to reflect distinct domains of Xist-mediated suppression. Our data has allowed us to assemble a comprehensive inventory of the epigenetic mechanisms utilized in eutherian mammals to maintain parent-specific imprinting, including an expanded view of the placental lineage that comprises multiple unique pathways.
Neurodegenerative and functional signatures of the cerebellar cortex in m.3243A>G patients
Authors: Haast Roy AM. , De Coo Irenaeus FM. , Ivanov Dimo , Khan Ali R , Jansen Jacobus FA. , Smeets Hubert JM. , Uludağ Kâmil 
Published: May 2021

AbstractMutations of the mitochondrial DNA are an important cause of inherited diseases that can severely affect the tissue’s homeostasis and integrity. The m.3243A>G mutation is the most commonly observed across mitochondrial disorders and is linked to multisystemic complications, including cognitive deficits. In line with in vitro experiments demonstrating the m.3243A>G’s negative impact on neuronal energy production and integrity, m.3243A>G patients show cerebral gray matter tissue changes. However, its impact on the most neuron-dense, and therefore energy-consuming brain structure – the cerebellum – remains elusive.In this work, we used high resolution structural and functional data acquired using 7 Tesla MRI to characterize the neurodegenerative and functional signatures of the cerebellar cortex in m.3243A>G patients. Our results reveal altered tissue integrity within distinct clusters across the cerebellar cortex, apparent by their significantly reduced volume and longitudinal relaxation rate compared to healthy controls, indicating macroscopic atrophy and microstructural pathology. Spatial characterization reveals that these changes occur especially in regions related to the frontoparietal brain network that is involved in information processing and selective attention. In addition, based on resting-state fMRI data, these clusters exhibit reduced functional connectivity to frontal and parietal cortical regions, especially in patients characterized by (i) a severe disease phenotype and (ii) reduced information processing speed and attention control.Combined with our previous work, these results provide insight into the neuropathological changes and a solid base to guide longitudinal studies aimed to track disease progression.
The impact of multiple species invasion on soil and plant communities increases with invader diversity
Authors: Dušanka Vujanović , Gianalberto Losapio , Stanko Milić , Dubravka Milić 
Published: May 2021

AbstractDespite increasing evidence indicating that invasive species are harming ecological systems and processes, impacts of multiple invasions, and the linkages between these events and changes in vegetation and soil are inadequately documented and remain poorly understood. Addressing multiple invasions would help to highlight high priority invaders and would aid in designing more effective control strategies, contributing to environmental restoration and sustainability. In this work, we tested the impact of three concurring invasive plant species,Amorpha fruticosa, Fraxinus pennsylvanicaandAcer negundo, on soil conditions and native plant diversity. The research was conducted in riparian ecosystem and included the following treatments: (1) co-occurrence of the three invasive plant species, (2) occurrence of a single invasive species, and (3) control, i.e., absence of invasive species. Our findings revealed that the impact of invasive plants on soil properties and native plant diversity is magnified by their co-occurrence. Soil in mixed plots (those populated with all three invaders) contained much higher levels of nitrifying bacteria (NB), organic matter (Om), nitrogen (N), and carbon (C) as well as lower carbon to nitrogen ratio (C:N) levels, compared to single species invaded plots and control plots. Mixed plots were also characterized by reduced native plant diversity compared to single species invaded and control plots. Differences in soil conditions and native plant diversity revealed the interactive potential of invasive plants in depleting biodiversity, and thus in affecting ecological and biogeochemical processes. Our results highlight the need to study the impact of multispecies invasion and suggest that sites in riparian areas affected by co-occurring invaders, should be prioritized for ecosystem restoration.
Genetic diversity and connectivity of the Ostreid herpesvirus 1 populations in France: a first attempt to phylogeographic inference for a marine mollusc disease
Authors: Delmotte Jean , Pelletier Camille , Morga Benjamin , Galinier Richard , Petton Bruno , Lamy Jean-Baptiste , Kaltz Oliver , Avarre Jean-Christophe , Jacquot Maude , Montagnani Caroline , Escoubas Jean-Michel 
Published: May 2021

AbstractThe genetic diversity of viral populations is a key driver of the spatial and temporal diffusion of viruses; yet, studying the diversity of whole genomes from natural populations still remains a challenge. Phylodynamic approaches are commonly used for RNA viruses harboring small genomes, but have only rarely been applied to DNA viruses with larger genomes. Here, we used the Pacific Oyster Mortality Syndrome (POMS, a disease that affects oyster farms around the world) as a model to study the genetic diversity of its causative agent, the Ostreid herpesvirus 1 (OsHV-1) in the three main French oyster-farming areas. Using ultra-deep sequencing on individual moribund oysters and an innovative combination of bioinformatics tools, wede novoassembled 21 OsHV-1 new genomes. Combining quantification of major and minor genetic variations, phylogenetic analysis and ancestral state reconstruction of discrete traits approaches; we assessed the connectivity of OsHV-1 viral populations between the three oyster-farming areas. Our results suggest that the Marennes- Oléron Bay represents the main source of OsHV-1 diversity, from where the virus has dispersed to other farming areas, a scenario consistent with current practices of oyster transfers in France. We demonstrate that phylodynamic approaches can be applied to aquatic DNA viruses to determine how epidemiological, immunological, and evolutionary processes act and potentially interact to shape their diversity patterns.ImportancePhylogeography is a field of research that attempts to reconstruct the relationships between individual genotypes within a species and then correlate these genealogical relationships with their geographic and temporal origin. This field of research has become an essential step in the understanding of pandemics, in particular to determine the origin, spread and evolution of a pathogen as currently illustrated in studies on viral pandemics. However, because phylogeographic analyses are based on genome variation, stable genomes yield less information than labile genomes. Accordingly, viruses with double-stranded DNA (dsDNA) genomes generally have lower nucleotide diversity than RNA viruses. In this study, by combining the use of both major and minor genetic variations with phylogeographic analyses of the oyster herpesvirus OsHV-1, we highlight genealogical relationships that are not depicted in phylogenetic trees based on consensus viral genomes only. These data offer a plausible scenario reflecting the origin and spread of OsHV-1 populations between oyster- farming sites.
A comparison of tools for copy-number variation detection in germline whole exome and whole genome sequencing data
Authors: Gabrielaite Migle , Torp Mathias Husted , Rasmussen Malthe Sebro , Andreu-Sánchez Sergio , Vieira Filipe Garrett , Pedersen Christina Bligaard , Kinalis Savvas , Madsen Majbritt Busk , Yde Christina Westmose , Rønn Olsen Lars , Marvig Rasmus L. , Østrup Olga , Rossing Maria , Nielsen Finn Cilius , Winther Ole , Bagger Frederik Otzen 
Published: May 2021

AbstractBackgroundCopy-number variations (CNVs) have important clinical implications for several diseases and cancers. The clinically relevant CNVs are hard to detect because CNVs are common structural variations that define large parts of the normal human genome. CNV calling from short-read sequencing data has the potential to leverage available cohort studies and allow full genomic profiling in the clinic without the need for additional data modalities. Questions regarding performance of CNV calling tools for clinical use and suitable sequencing protocols remain poorly addressed, mainly because of the lack of good reference data sets.MethodsWe reviewed 50 popular CNV calling tools and included 11 tools for benchmarking in a unique reference cohort encompassing 39 whole genome sequencing (WGS) samples paired with analysis by the current clinical standard —SNP-array based CNV calling. Additionally, for nine of these samples we performed whole exome sequencing (WES) performed, in order to address the effect of sequencing protocol on CNV calling. Furthermore, we included Gold Standard reference sample NA12878, and tested 12 samples with CNVs confirmed by multiplex ligation-dependent probe amplification (MLPA).ResultsTool performance varied greatly in the number of called CNVs and bias for CNV lengths. Some tools had near-perfect recall of CNVs from arrays for some samples, but poor precision. Filtering output by CNV ranks from tools did not salvage precision. Several tools had better performance patterns for NA12878, and we hypothesize that this is the result of overfitting during the tool development.ConclusionsWe suggest combining tools with the best recall: GATK gCNV, Lumpy, DELLY, and cn.MOPS. These tools also capture different CNVs. Further improvements in precision requires additional development of tools, reference data sets, and annotation of CNVs, potentially assisted by the use of background panels for filtering of frequently called variants.