bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Strand-biased Transcription of SARS-CoV-2 and Unbalanced Inhibition by Remdesivir
Authors: Zhao Yan , Sun Jing , Li Yunfei , Li Zhengxuan , Xie Yu , Feng Ruoqing , Zhao Jincun , Hu Yuhui 
Published: October 2020

AbstractSARS-CoV-2, a positive single-stranded RNA virus, caused the COVID-19 pandemic. During the viral replication and transcription, the RNA dependent RNA polymerase (RdRp) “jumps” along the genome template, resulting in discontinuous negative-stranded transcripts. In other coronaviruses, the negative strand RNA was found functionally relevant to the activation of host innate immune responses. Although the sense-mRNA architectures of SARS-CoV-2 were reported, its negative strand was unexplored. Here, we deeply sequenced both strands of RNA and found SARS-CoV-2 transcription is strongly biased to form the sense strand. During negative strand synthesis, apart from canonical sub-genomic ORFs, numerous non-canonical fusion transcripts are formed, driven by 3-15 nt sequence homology scattered along the genome but more prone to be inhibited by SARS-CoV-2 RNA polymerase inhibitor Remdesivir. The drug also represses more of the negative than the positive strand synthesis as supported by a mathematic simulation model and experimental quantifications. Overall, this study opens new sights into SARS-CoV-2 biogenesis and may facilitate the anti-viral vaccine development and drug design.One Sentence SummaryStrand-biased transcription of SARS-CoV-2.
Large-scale analysis ofDrosophilacore promoter function using synthetic promoters
Authors: Qi Zhan , Jung Christophe , Bandilla Peter , Ludwig Claudia , Heron Mark , Kiesel Anja Sophie , Philippou-Massier Julia , Nikolov Miroslav , Renna Alessio , Schnepf Max , Unnerstall Ulrich , Soeding Johannes , Gaul Ulrike 
Published: October 2020

SUMMARYThe core promoter, the region immediately surrounding the transcription start site, plays a central role in setting metazoan gene expression levels, but how exactly it ‘computes’ expression remains poorly understood. To dissect core promoter function, we carried out a comprehensive structure-function analysis to measure synthetic promoters’ activities, with and without an external stimulus (hormonal activation). By using robotics and a dual-luciferase reporter assay, we tested ∼3000 mutational variants representing 19 differentDrosophila melanogasterpromoter architectures. We explored the impact of different types of mutations, including knockout of individual sequence motifs and motif combinations, variations of motif strength, positioning, and flanking sequences. We observe strong effects of the mutations on activity, and a linear combination of the individual motif features can largely account for the combinatorial effects on core promoter activity. Our findings shed new light on the quantitative assessment of gene expression, a fundamental process in all metazoans.
Emergence of prefrontal neuron maturation properties by training recurrent neural networks in cognitive tasks
Authors: Liu Yichen Henry , Zhu Junda , Constantinidis Christos , Zhou Xin 
Published: October 2020

ABSTRACTWorking memory and response inhibition are functions that mature relatively late in life, after adolescence, paralleling the maturation of the prefrontal cortex. The link between behavioral and neural maturation is not obvious, however, making it challenging to understand how neural activity underlies the maturation of cognitive function. To gain insights into the nature of observed changes in prefrontal activity between adolescence and adulthood, we investigated the progressive changes in unit activity of Recurrent Neural Networks (RNNs) as they were trained to perform working memory and response inhibition tasks. These included increased delay period activity during working memory tasks, and increased activation in antisaccade tasks. These findings reveal universal properties underlying the neuronal computations behind cognitive tasks and explicate the nature of changes that occur as the result of developmental maturation.
A multi-platform reference for somatic structural variation detection
Authors: Valle-Inclan Jose Espejo , Besselink Nicolle J.M. , de Bruijn Ewart , Cameron Daniel L. , Ebler Jana , Kutzera Joachim , van Lieshout Stef , Marschall Tobias , Nelen Marcel , Pang Andy Wing Chun , Priestley Peter , Renkens Ivo , Roemer Margaretha G.M. , van Roosmalen Markus J. , Wenger Aaron M. , Ylstra Bauke , Fijneman Remond J.A. , Kloosterman Wigard P. , Cuppen Edwin 
Published: October 2020

AbstractAccurate detection of somatic structural variation (SV) in cancer genomes remains a challenging problem. This is in part due to the lack of high-quality gold standard datasets that enable the benchmarking of experimental approaches and bioinformatic analysis pipelines for comprehensive somatic SV detection. Here, we approached this challenge by genome-wide somatic SV analysis of the paired melanoma and normal lymphoblastoid COLO829 cell lines using four different technologies: Illumina HiSeq, Oxford Nanopore, Pacific Biosciences and 10x Genomics. Based on the evidence from multiple technologies combined with extensive experimental validation, including Bionano optical mapping data and targeted detection of candidate breakpoint junctions, we compiled a comprehensive set of true somatic SVs, comprising all SV types. We demonstrate the utility of this resource by determining the SV detection performance of each technology as a function of tumor purity and sequence depth, highlighting the importance of assessing these parameters in cancer genomics projects and data analysis tool evaluation. The reference truth somatic SV dataset as well as the underlying raw multi-platform sequencing data are freely available and are an important resource for community somatic benchmarking efforts.
Population scale nucleic acid delivery toCaenorhabditis elegansvia electroporation
Authors: Khodakova Anastasia S. , Vilchis Daniela Vidal , Amanor Ferdinand , Samuel Buck S. 
Published: October 2020

ABSTRACTThe free-living nematodeC.elegansremains one of the most robust and flexible genetic systems for inter-rogating the complexities of animal biology. Targeted genetic manipulations, such as RNA interference (RNAi), CRISPR/Cas9- or array-based transgenesis, all depend on initial delivery of nucleic acids. Delivery of dsRNA by feeding can be effective, but expression inE. coliis not conducive to experiments intended to remain sterile or with defined microbial communities. Soaking-based delivery requires prolonged exposure of animals to high material concentrations without a food source and is of limited throughput. Last, microinjection of individual animals can precisely deliver materials to animals’ germlines, but is limited by the need to target and inject each animal one-by-one. Thus, we sought to address some of these challenges in nucleic acid delivery by developing a population-scale delivery method. We demonstrate efficient electroporation-mediated delivery of dsRNA throughout the worm and effective RNAi-based silencing, including in the germline. Finally, we show that guide RNA delivered by electroporation can be utilized by transgenic Cas9 expressing worms for population-scale genetic targeting. Together, these methods expand the scale and scope of genetic methodologies that can be applied to theC.eleganssystem.
Natural selection reverses the exaggeration of a male sexually selected trait, which increases female fitness
Authors: Okada Kensuke , Katsuki Masako , Sharma Manmohan D. , Kiyose Katsuya , Seko Tomokazu , Okada Yasukazu , Wilson Alastair J. , Hosken David J. 
Published: October 2020

AbstractTheory shows how sexual selection can exaggerate male traits beyond naturally selected optima and also how natural selection can ultimately halt trait elaboration. Empirical evidence supports this theory, but to date, there have been no experimental evolution studies directly testing this logic, and little examination of possible associated effects on female fitness. Here we used experimental evolution of replicate populations of broad-horned flour-beetles to test for evolutionary effects of sex-specific predation on an exaggerated sexually selected male trait, while also testing for effects on female lifetime reproductive success. We found that populations subjected to male-specific predation evolved smaller sexually selected traits and this indirectly increased female fitness, seemingly through intersexual genetic correlations we documented. Predation solely on females had no effects. Our findings support fundamental theory, but also reveal novel outcomes when natural selection targets sex-limited sexually selected characters.
Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes
Authors: Zerbi V. , Pagani M. , Markicevic M. , Matteoli M. , Pozzi D. , Fagiolini M. , Bozzi Y. , Galbusera A. , Scattoni ML , Provenzano G. , Banerjee A. , Helmchen F. , Albert Basson M. , Ellegood J. , Lerch J. P. , Rudin M. , Gozzi A. , Wenderoth N. 
Published: October 2020

AbstractAutism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy and relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation of fMRI-based connectivity in the mouse, in which specific ASD-relevant mutations can be isolated and modelled minimizing environmental contributions. By performing brain-wide connectivity mapping across 16 mouse mutants, we show that different ASD-associated etiologies cause a broad spectrum of connectional abnormalities in which diverse, often diverging, connectivity signatures are recognizable. Despite this heterogeneity, the identified connectivity alterations could be classified into four subtypes characterized by discrete signatures of network dysfunction. Our findings show that etiological variability is a key determinant of connectivity heterogeneity in ASD, hence reconciling conflicting findings in clinical populations. The identification of etiologically-relevant connectivity subtypes could improve diagnostic label accuracy in the non-syndromic ASD population and paves the way for personalized treatment approaches.
Nanoscape, a data-driven 3D real-time interactive virtual cell environment
Authors: Kadir Shereen R. , Lilja Andrew , Gunn Nick , Strong Campbell , Hughes Rowan T. , Bailey Benjamin J. , Rae James , Parton Robert G. , McGhee John 
Published: October 2020

AbstractKnowledge of cellular and structural biology has reached unprecedented levels of detail. In conjunction with advances in 3D computer visualisation techniques this has allowed exploration of cellular ultrastructure and environments by a virtual user. The extraction and integration of relevant scientific information, along with consideration of the best representation of data, is often a bottleneck in the visualisation process for many 3D biomedical artists. Here we introduce ‘Nanoscape’, a collaborative project between 3D computer artists, computer graphics developers, and cell biologists that enables a user to navigate a cell in a complex 3D computer visualised environment. We combine actual data from various scientific disciplines (including structural biology, cell biology and multiple microscopic techniques) and apply artistic expression and design aesthetics to create a unique new experience where a real-time virtual explorer can traverse a cell surface, observe and interact with a more scientifically accurate cell surface environment.
Integrated characterization of SARS-CoV-2 genome, microbiome, antibiotic resistance and host response from single throat swabs
Authors: Lu Bo , Yan Yi , Dong Liting , Han Lingling , Liu Yawei , Yu Junping , Chen Jianjun , Yi Danyang , Zhang Meiling , Wang Chao , Wang Runkun , Wang Dengpeng , Wei Hongping , Liu Di , Yi Chengqi 
Published: October 2020

AbstractThe ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, poses a severe threat to humanity. Rapid and comprehensive analysis of both pathogen and host sequencing data is critical to track infection and inform therapies. In this study, we performed unbiased metatranscriptomic analysis of clinical samples from COVID-19 patients using a newly-developed RNA-seq library construction method (TRACE-seq), which utilizes tagmentation activity of Tn5 on RNA/DNA hybrids. This approach avoids the laborious and time-consuming steps in traditional RNA-seq procedure, and hence is fast, sensitive and convenient. We demonstrated that TRACE-seq allowed integrated characterization of full genome information of SARS-CoV-2, putative pathogens causing coinfection, antibiotic resistance and host response from single throat swabs. We believe that the integrated information will deepen our understanding of pathogenesis and improve diagnostic accuracy for infectious diseases.
Latent Feature Representations for Human Gene Expression Data Improve Phenotypic Predictions
Authors: Pantazis Yannis , Tselas Christos , Lakiotaki Kleanthi , Lagani Vincenzo , Tsamardinos Ioannis 
Published: October 2020

AbstractHigh-throughput technologies such as microarrays and RNA-sequencing (RNA-seq) allow to precisely quantify transcriptomic profiles, generating datasets that are inevitably high-dimensional. In this work, we investigate whether the whole human transcriptome can be represented in a compressed, low dimensional latent space without loosing relevant information. We thus constructed low-dimensional latent feature spaces of the human genome, by utilizing three dimensionality reduction approaches and a diverse set of curated datasets. We applied standard Principal Component Analysis (PCA), kernel PCA and Autoencoder Neural Networks on 1360 datasets from four different measurement technologies. The latent feature spaces are tested for their ability to (a) reconstruct the original data and (b) improve predictive performance on validation datasets not used during the creation of the feature space. While linear techniques show better reconstruction performance, nonlinear approaches, particularly, neural-based models seem to be able to capture non-additive interaction effects, and thus enjoy stronger predictive capabilities. Our results show that low dimensional representations of the human transcriptome can be achieved by integrating hundreds of datasets, despite the limited sample size of each dataset and the biological / technological heterogeneity across studies. The created space is two to three orders of magnitude smaller compared to the raw data, offering the ability of capturing a large portion of the original data variability and eventually reducing computational time for downstream analyses.
Early maternal loss affects diurnal cortisol slopes in immature but not mature wild chimpanzees
Authors: Girard-Buttoz Cédric , Tkaczynski Patrick J. , Samuni Liran , Fedurek Pawel , Gomes Cristina , Löhrich Therese , Manin Virgile , Preis Anna , Valé Prince , Deschner Tobias , Wittig Roman M. , Crockford Catherine 
Published: October 2020

AbstractIn mammals, early life adversity negatively affects survival and reproductive success. A key causal mechanism is proposed by the biological embedding model which posits that adversity experienced early in life has deleterious consequences on individual physiology across the lifespan. In particular, early life adversity is expected to be a severe stressor leading to long-term alteration of the hypothalamic pituitary adrenal (HPA) axis activity. Here we tested this idea by assessing whether, as in humans, maternal loss had short and long-term impacts on orphan chimpanzee urinary cortisol levels and diurnal urinary cortisol slopes, as an indicator of the HPA axis functioning. We used 18 years of data on 50 immature and 28 mature male wild chimpanzees belonging to four communities in Taï National Park, Ivory Coast. Immature orphans who experienced early maternal loss had diurnal cortisol slopes characterised by higher early morning and late afternoon cortisol levels indicative of high activation of the HPA axis. Recently orphaned immatures had higher cortisol levels than other immatures, possibly reflecting social and nutritional stress. However, unlike in humans, we did not find significantly different cortisol profiles in orphan and non-orphan adult male chimpanzees. Our study highlights that long-term alteration of stress physiology related to early life adversity may not be viable in some wild animal populations and/or that chimpanzees, as humans, may have access to mechanisms that buffer this physiological stress, such as adoption. Our results suggest that biological embedding of altered HPA axis function is unlikely to be a mechanism contributing to the demonstrated long-term fitness consequences of maternal loss, such as reduced reproductive success, in wild long-lived mammals.
Multiple decisions about one object involve parallel sensory acquisition but time-multiplexed evidence incorporation
Authors: Kang Yul HR , Löffler Anne , Jeurissen Danique , Zylberberg Ariel , Wolpert Daniel M , Shadlen Michael N 
Published: October 2020

AbstractThe brain is capable of processing several streams of information that bear on different aspects of the same problem. Here we address the problem of making two decisions about one object, by studying difficult perceptual decisions about the color and motion of a dynamic random dot display. We find that the accuracy of one decision is unaffected by the difficulty of the other decision. However, the response times reveal that the two decisions do not form simultaneously. We show that both stimulus dimensions are acquired in parallel for the initial ~0.1 s but are then incorporated serially in time-multiplexed bouts. Thus there is a bottleneck that precludes updating more than one decision at a time, and a buffer that stores samples of evidence while access to the decision is blocked. We suggest that this bottleneck is responsible for the long timescales of many cognitive operations framed as decisions.
iTRAQ-Based Proteomic Profiling of PLC-Mediated Expression of 20E-Induced Protein inApolygus lucorum(Meyer-Dür)
Authors: Tan Yong-An , Zhao Xu-Dong , Zhao Jing , Ji Qin-Qin , Xiao Liu-Bin , Hao De-Jun 
Published: October 2020

AbstractThe polyphagous pestApolygus lucorumhas become the dominant insect inBacillus thuringiensis(Bt) cotton fields. The hormone 20-hydroxyecdysone (20E) regulates multiple events in insect development and physiology. 20E responses are controlled by pathways triggered by phospholipase C (PLC)-associated proteins. However, 20E-modulated genes whose expression is affected by PLC remain unknown. Here, isobaric tag for relative and absolute quantitation (iTRAQ) and immunoblot were carried out for comparing differentially expressed proteins (DEPs) inA. lucorumin response to 20E and the PLC inhibitor U73122, respectively. Totally 1624 DEPs were, respectively, found in the 20E/control, U73122/control, and 20E+U73122/control groups. Venn diagram analysis further revealed 8 DEPs that were shared among the three groups. Immunoblot validated these findings, which corroborated and highlighted the reliability of proteomics. KEGG enrichment analysis showed that the DEPs were included in diverse signaling pathways. The largest portion of DEPs among the three groups were categorized in metabolic pathways. In addition, DEPs among the three groups were also found to regulate the Ras-MAPK and PI3K-AKT pathways. This is the first time that iTRAQ was carried out to assess proteome alteration inA. lucorumnymphs in response to 20E and a PLC inhibitor. These findings provide novel insights into protein expression inA. lucorumin response to 20E, and a more comprehensive understanding of the function of PLC in 20E signal transduction.
Synaptic diversity naturally arises from neural decoding of heterogeneous populations
Authors: Yates Jacob L. , Scholl Benjamin 
Published: October 2020

AbstractThe synaptic inputs to single cortical neurons exhibit substantial diversity in their sensory-driven activity. What this diversity reflects is unclear, and appears counter-productive in generating selective somatic responses to specific stimuli. We propose that synaptic diversity arises because neurons decode information from upstream populations. Focusing on a single sensory variable, orientation, we construct a probabilistic decoder that estimates the stimulus orientation from the responses of a realistic, hypothetical input population of neurons. We provide a straightforward mapping from the decoder weights to real excitatory synapses, and find that optimal decoding requires diverse input weights. Analytically derived weights exhibit diversity whenever upstream input populations consist of noisy, correlated, and heterogeneous neurons, as is typically foundin vivo. In fact, in silico weight diversity was necessary to accurately decode orientation and matched the functional heterogeneity of dendritic spines imaged in vivo. Our results indicate that synaptic diversity is a necessary component of information transmission and reframes studies of connectivity through the lens of probabilistic population codes. These results suggest that the mapping from synaptic inputs to somatic selectivity may not be directly interpretable without considering input covariance and highlights the importance of population codes in pursuit of the cortical connectome.
The Effects of Inter-Individual Biological Differences and Taphonomic Alteration on Human Bone Protein Profiles: Implications for the Development of PMI/AAD Estimation Methods
Authors: Mickleburgh Hayley L. , Schwalbe Ed , Mizukami Haruka , Sellitto Federica , Starace Sefora , Wescott Daniel J. , Carter David O. , Procopio Noemi 
Published: October 2020

AbstractBone proteomics studies using animal proxies and skeletonized human remains have delivered encouraging results in the search for potential biomarkers for precise and accurate post-mortem interval (PMI) and the age-at-death (AAD) estimation in medico-legal investigations. At present, however, the effects of inter-individual biological differences and taphonomic alteration on recovered human bone protein profiles are not well understood. This study investigated the human bone proteome in four human body donors studied throughout decomposition outdoors. The effects of ageing phenomena (in vivoand post-mortem), and intrinsic and extrinsic variables on the variety and abundancy of the bone proteome were assessed. Results identified a new potential biomarker for PMI estimation, as well as three potential biomarkers for AAD estimation. The results also suggest that bone mineral density (BMD) may be an important variable affecting the survival and extraction of proteins.Highlights- CO3, CO9, COBA2, CO3A1, MGP, PGS2 and TTHY are potential biomarkers for post-mortem interval estimation in skeletonized human remains- FETUA, ALBU and OLFL3 are potential biomarkers for age-at-death estimation in human remains- Taphonomic and biological variables play a significant role in survival and extraction rates of proteins in bone- Bone mineral density may affect survival of proteins in bone, probably due to the effects of the mineral matrix on the movement of decomposer microbes- Higher bone mineral density may affect the survival and the extraction rate of collagen and mineral-binding proteins