bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract
Authors: Zaeck Luca M. , Scheibner David , Sehl Julia , Müller Martin , Hoffmann Donata , Beer Martin , Abdelwhab Elsayed M. , Mettenleiter Thomas C. , Breithaupt Angele , Finke Stefan 
Published: October 2020

AbstractThe visualization of viral pathogens in infected tissues is an invaluable tool to understand spatial virus distribution, localization, and cell tropismin vivo. Commonly, virus-infected tissues are analyzed using conventional immunohistochemistry in paraffin-embedded thin sections. Here, we demonstrate the utility of volumetric three-dimensional (3D) immunofluorescence imaging using tissue optical clearing and light sheet microscopy to investigate host-pathogen interactions of pandemic SARS-CoV-2 in ferrets at a mesoscopic scale. The superior spatial context of large, intact samples (> 150 mm3) allowed detailed quantification of interrelated parameters like focus-to-focus distance or SARS-CoV-2-infected area, facilitating an in-depth description of SARS-CoV-2 infection foci. Accordingly, we could confirm a preferential infection of the ferret upper respiratory tract by SARS-CoV-2 and emphasize a distinct focal infection pattern in nasal turbinates. Conclusively, we present a proof-of-concept study for investigating critically important respiratory pathogens in their spatial tissue morphology and demonstrate the first specific 3D visualization of SARS-CoV-2 infection.
GenOrigin: A Comprehensive Protein-coding Gene Origination Database on the Evolutionary Timescale of Life
Authors: Tong Yi-Bo , Shi Meng-Wei , Qian Sheng Hu , Chen Yu-Jie , Luo Zhi-Hui , Tu Yi-Xuan , Chen Chunyan , Chen Zhen-Xia 
Published: October 2020

ABSTRACTThe origination of new genes contributes to the biological diversity of life. New genes may quickly build their own network in the genomes, exert important functions, and generate novel phenotypes. Dating gene age and inferring the origination mechanisms of new genes, like primate-specific gene, is the basis for the functional study of the genes. However, no comprehensive resource of gene age estimates across species is available. Here, we systematically dated the age of 9,102,113 protein-coding genes from 565 species in the Ensembl and Ensembl Genomes databases, including 82 bacteria, 57 protists, 134 fungi, 58 plants, 56 metazoa, and 178 vertebrates, using protein-family-based pipeline with Wagner parsimony algorithm. We also collected gene age estimate data from other studies and uniformed the gene age estimates to time ranges in million years for comparison across studies. All the data were cataloged into GenOrigin (http://genorigin.chenzxlab.cn/), a userfriendly new database of gene age estimates, where users can browse gene age estimates by species, age and gene ontology. In GenOrigin, the information such as gene age estimates, annotation, gene ontology, ortholog and paralog, as well as detailed gene presence/absence views for gene age inference based on the species tree with evolutionary timescale, was provided to researchers for exploring gene functions.
Therapy-induced normal tissue damage promotes breast cancer metastasis
Authors: Perkins Douglas W. , Steiner Ivana , Haider Syed , Robertson David , Buus Richard , O’Leary Lynda , Isacke Clare M. 
Published: October 2020

AbstractDisseminated tumour cells frequently exhibit a period of dormancy that renders them insensitive to targeting by chemotherapeutic agents, conversely the systemic delivery of chemotherapies can result in normal tissue damage. Using multiple mouse and human breast cancer models, we demonstrate that prior chemotherapy administration enhances metastatic colonisation and outgrowth.In vitro, chemotherapy treatment induces fibroblast senescence associated with a senescence associated secretory phenotype (SASP) that accelerates 3D tumour spheroid growth. These chemotherapy-treated fibroblasts, and their pro-tumourigenic function, can be effectively eliminated by targeting the anti-apoptotic protein BCL-xL.In vivo, chemotherapy treatment induces SASP expression in normal tissues, however the accumulation of senescent cells is limited and BCL-xL inhibitors are unable to reduce chemotherapy-enhanced metastasis. This likely reflects that chemotherapy-exposed normal tissues support metastatic colonisation via the secretion of pro-tumourigenic factors and remodelling of the extracellular matrix, but that damaged stromal cells do not enter a full BCL-xL-dependent senescence or switch their dependency to other anti-apoptotic BCL-2 family members. In summary, this study highlights the role of the metastatic microenvironment in controlling outgrowth of disseminated tumour cells and the need to identify novel therapeutic approaches to effectively limit the pro-tumourigenic effects of chemotherapy-induced normal tissue damage.
Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19
Authors: Tindle Courtney , Fuller MacKenzie , Fonseca Ayden , Taheri Sahar , Ibeawuchi Stella-Rita , Beutler Nathan , Katkar Gajanan D. , Claire Amanraj , Castillo Vanessa , Hernandez Moises , Russo Hana , Duran Jason , Crotty Alexander Laura E. , Tipps Ann , Lin Grace , Thistlethwaite Patricia A. , Chattopadhyay Ranajoy , Rogers Thomas F. , Sahoo Debashis , Ghosh Pradipta , Das Soumita 
Published: October 2020

SummarySARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to createin vitrolung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection, whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19, which can be immediately utilized to investigate COVID-19 pathogenesis and vet new therapies and vaccines.GRAPHIC ABSTRACTHIGHLIGHTSHuman lung organoids with mixed proximodistal epithelia are createdProximal airway cells are critical for viral infectivityDistal alveolar cells are important for emulating host responseBoth are required for the overzealous response in severe COVID-19IN BRIEFAn integrated stem cell-based disease modeling and computational approach demonstrate how both proximal airway epithelium is critical for SARS-CoV-2 infectivity, but distal differentiation of alveolar pneumocytes is critical for simulating the overzealous host response in fatal COVID-19.
Hybrid E/M phenotype(s) and stemness: a mechanistic connection embedded in network topology
Authors: Pasani Satwik , Sahoo Sarthak , Jolly Mohit Kumar 
Published: October 2020

AbstractMetastasis remains an unsolved clinical challenge. Two crucial features of metastasizing cancer cells are a) their ability to dynamically move along the epithelial-hybrid-mesenchymal spectrum and b) their tumor-initiation potential or stemness. With increasing functional characterization of hybrid epithelial/mesenchymal (E/M) phenotypes along the spectrum, recentin vitroandin vivostudies have suggested an increasing association of hybrid E/M phenotypes with stemness. However, the mechanistic underpinnings enabling this association remain unclear. Here, we develop a mechanism-based mathematical modeling framework that interrogates the emergent nonlinear dynamics of the coupled network modules regulating E/M plasticity (miR-200/ZEB) and stemness (LIN28/let-7). Simulating the dynamics of this coupled network across a large ensemble of parameter sets, we observe that hybrid E/M phenotype(s) are more likely to acquire stemness relative to ‘pure’ epithelial or mesenchymal states. We also integrate multiple ‘phenotypic stability factors’ (PSFs) that have been shown to stabilize hybrid E/M phenotypes bothin silicoandin vitro– such as OVOL1/2, GRHL2, and NRF2 – with this network, and demonstrate that the enrichment of hybrid E/M phenotype(s) with stemness is largely conserved in the presence of these PSFs. Thus, our results offer mechanistic insights into recent experimental observations of hybrid E/M phenotype(s) being essential for tumor-initiation and highlight how this feature is embedded in the underlying topology of interconnected EMT and stemness networks.
Gulf of Mexico blue hole harbors high levels of novel microbial lineages
Authors: Patin NV , Dietrich ZA , Stancil A , Quinan M , Beckler JS , Hall ER , Culter J , Smith CG , Taillefert M , Stewart FJ 
Published: October 2020

AbstractExploration of oxygen-depleted marine environments has consistently revealed novel microbial taxa and metabolic capabilities that expand our understanding of microbial evolution and ecology. Marine blue holes are shallow karst formations characterized by low oxygen and high organic matter content. They are logistically challenging to sample, and thus our understanding of their biogeochemistry and microbial ecology is limited. We present a metagenomic characterization of Amberjack Hole on the Florida continental shelf (Gulf of Mexico). Dissolved oxygen became depleted at the hole’s rim (32 m water depth), remained low but detectable in an intermediate hypoxic zone (40-75 m), and then increased to a secondary peak before falling below detection in the bottom layer (80-110 m), concomitant with increases in nutrients, dissolved iron, and a series of sequentially more reduced sulfur species. Microbial communities in the bottom layer contained heretofore undocumented levels of the recently discovered phylum Woesearchaeota (up to 58% of the community), along with lineages in the bacterial Candidate Phyla Radiation (CPR). Thirty-one high-quality metagenome-assembled genomes (MAGs) showed extensive biochemical capabilities for sulfur and nitrogen cycling, as well as for resisting and respiring arsenic. One uncharacterized gene associated with a CPR lineage differentiated hypoxic from anoxic zone communities. Overall, microbial communities and geochemical profiles were stable across two sampling dates in the spring and fall of 2019. The blue hole habitat is a natural marine laboratory that provides opportunities for sampling taxa with under-characterized but potentially important roles in redox-stratified microbial processes.
The Genomic History of the Middle East
Authors: Almarri Mohamed A. , Haber Marc , Lootah Reem A. , Hallast Pille , Turki Saeed Al , Martin Hilary C. , Xue Yali , Tyler-Smith Chris 
Published: October 2020

AbstractThe Middle East is an important region to understand human evolution and migrations, but is underrepresented in genetic studies. We generated and analysed 137 high-coverage physically-phased genome sequences from eight Middle Eastern populations using linked-read sequencing. We found no genetic traces of early expansions out-of-Africa in present-day populations, but find Arabians have elevated Basal Eurasian ancestry that dilutes their Neanderthal ancestry. A divergence in population size within the region starts before the Neolithic, when Levantines expanded while Arabians maintained small populations that could have derived ancestry from local epipaleolithic hunter-gatherers. All populations suffered a bottleneck overlapping documented aridification events, while regional migrations increased genetic structure, and may have contributed to the spread of the Semitic languages. We identify new variants that show evidence of selection, some dating from the onset of the desert climate in the region. Our results thus provide detailed insights into the genomic and selective histories of the Middle East.
Functional Exploration of Copy Number Alterations in aDrosophilaModel of Triple Negative Breast Cancer
Authors: Diaz Jennifer E. L. , Barcessat Vanessa , Bahamon Christian , Cagan Ross L. 
Published: October 2020

AbstractAccounting for 10-20% of breast cancer cases, TNBC is associated with a disproportionate number of breast cancer deaths. Despite recent progress, many patients fail to respond to current targeted therapies. Responses to chemotherapy are variable, and the tumor characteristics that determine response are poorly understood. One challenge in studying TNBC is its genomic profile: outside ofTP53loss, most cases are characterized by copy number alterations (CNAs), making modeling the disease in whole animals challenging. We analyzed 186 previously identified CNA regions in breast cancer to rank genes within each region by likelihood of acting as a tumor driver. We characterized aDrosophilap53-Myc model of TNBC, demonstrating aspects of transformation. We then used this model to assess highly ranked genes, identifying 48 as functional drivers. To demonstrate the utility of this functional database, we combined six of these drivers with p53-Myc to generate six 3-hit genotypes. These 3-hit models showed increased aspects of transformation as well as resistance to the standard-of-care chemotherapeutic drug fluorouracil. Our work provides a functional database of CNA-associated TNBC drivers, and uses this database to support the model that increased genetic complexity leads to increased therapeutic resistance. Further, we provide a template for an integrated computational/whole animal approach to identify functional drivers of transformation and drug resistance within CNAs for other tumor types.
Derivation of human extended pluripotent stem cells in feeder-free condition
Authors: Zheng Ran , Geng Ting , Wu Dan-Ya , Zhang Tianzhe , He Hai-Nan , Wang Liyan , Du Haining , Zhang Donghui , Miao Yi-Liang , Jiang Wei 
Published: October 2020

SUMMARYHuman extended pluripotent stem cells (EPSCs), with bidirectional chimeric ability to contribute to both embryonic and extra-embryonic lineages, can be obtained and maintained by converting embryonic stem cells (ESCs) using chemicals. However, the transition system is based on inactivated mouse fibroblast, which greatly hinders the mechanistic studies of extended pluripotency and further applications. Here we reported a Matrigel-based feeder-free method to convert human ESCs and iPSCs into EPSCs and demonstrated the extended pluripotency in terms of molecular features, chimeric ability, and transcriptome. We further improved the protocol by applying chemicals targeting glycolysis and histone methyltransferase. Altogether, our data established a feeder-free system to generate human EPSCs and provided additional insights into the acquisition of extended pluripotency.
Architectural Affordance Impacts Human Sensorimotor Brain Dynamics
Authors: Djebbara Zakaria , Fich Lars Brorson , Gramann Klaus 
Published: October 2020

AbstractAction is a medium of collecting sensory information about the environment, which in turn is shaped by architectural affordances. Affordances characterize the fit between the physical structure of the body and capacities for movement and interaction with the environment, thus relying on sensorimotor processes associated with exploring the surroundings. Central to sensorimotor brain dynamics, the attentional mechanisms directing the gating function of sensory signals share neuronal resources with motor-related processes necessary to inferring the external causes of sensory signals. Such a predictive coding approach suggests that sensorimotor dynamics are sensitive to architectural affordances that support or suppress specific kinds of actions for an individual. However, how architectural affordances relate to the attentional mechanisms underlying the gating function for sensory signals remains unknown. Here we demonstrate that event-related desynchronization of alpha-band oscillations in parieto-occipital and medio-temporal regions covary with the architectural affordances. Source-level time-frequency analysis of data recorded in a motor-priming Mobile Brain/Body Imaging experiment revealed strong event-related desynchronization of the alpha band to originate from the posterior cingulate complex and bilateral parahippocampal areas. Our results firstly contribute to the understanding of how the brain resolves architectural affordances relevant to behaviour. Second, our results indicate that the alpha-band originating from the posterior cingulate complex covaries with the architectural affordances before participants interact with the environment. During the interaction, the bilateral parahippocampal areas dynamically reflect the affordable behaviour as perceived through the visual system. We conclude that the sensorimotor dynamics are developed for processing behaviour-relevant features in the designed environment.
Transovarial transmission fuels persistent infections of a core virome in the Chagas disease vector Rhodnius prolixus
Authors: de Brito Tarcísio Fontenele , Coelho Vitor Lima , Cardoso Maira Arruda , de Abreu Brito Ingrid Alexandre , Zenk Fides Lea , Iovino Nicola , Pane Attilio 
Published: October 2020

AbstractTriatomine assassin bugs comprise hematophagous insect vectors ofTrypanosoma cruzi, the causative agent of the Chagas disease. Although the microbiome of these species has been investigated to some extent, only one virus infectingTriatoma infestanshas been identified to date. Here, we describe for the first time seven (+) single-strand RNA viruses (RpV1-7) infectingRhodnius prolixus, a primary vector of the Chagas disease in Central and South America. We show that the RpVs belong to the Picorna-Calici, Permutotetra and Luteo-Sobemo clades and are vertically transmitted from the mothers to the progeny via transovarial transmission. Consistent with this, all the RpVs, except RpV2 that is related to the entomopathogenic Slow bee paralysis virus, established persistent infections in ourR. prolixuscolony. Furthermore, we show thatR. prolixusovaries express 22-nucleotide viral siRNAs (vsiRNAs), but not viral piRNAs, that originate from the processing of dsRNA intermediates during viral replication of the RpVs. Interestingly, the Permutotetra and Luteo-Sobemo viruses display shared pools of visRNAs that might provide the basis for a cross-immunity system. The vsiRNAs are maternally deposited in the eggs, where they likely contribute to reduce the viral load and protect the developing embryos. Our results unveil for the first time a complex core virome inR. prolixusand begin to shed light on the RNAi-based antiviral defenses in triatomines.Author summaryRhodnius prolixusis a triatomine insect and a primary vector ofTrypanosoma cruzi, the etiologic agent of the Chagas disease, in Central and South America. Despite the medical relevance, very little is known about the viruses that infect these so-called assassin bugs. In this study, we show for the first time that triatomines can support the concomitant infection of a variety of RNA viruses belonging to distantly related viral families. Remarkably, we show that the viruses are vertically transmitted from the mothers to the progeny via transovarial transmission. The detection of 22-nucleotide viral small interfering RNAs in mature eggs strongly suggests that RNAi mechanisms contribute to reduce the viral load during oogenesis and embryogenesis inR. prolixus, thus safeguarding the development of embryos and nymphs. In agreement with these findings, all the viruses, except one, could establish persistent infections in our colony. Our results substantially expand the knowledge of the virus complexity in triatomine species. This viral toolkit might be harnessed to develop novel insect population control strategies to reduce the diffusion of the Chagas disease.
No support for intra-nor inter-locus sexual conflict over mating latency and copulation duration in a polyandrous fruit fly
Authors: Collet Julie M. , Sztepanacz Jacqueline L 
Published: October 2020

AbstractThe total strength of sexual selection on males depends on the relationship between various components of pre- and post-copulatory fitness. Misalignment between male and female interests creates inter-locus sexual conflict, where the fitness of one sex is increased at the expense of the other. Although rarely considered, mating behaviours can also be genetically correlated between males and females, creating intra-locus sexual conflict, where beneficial alleles in one sex are costly when expressed in the other sex. How inter- and intra-locus sexual conflicts operate on the expression of mating behaviours remains little understood. Here, we study male attractiveness, mating latency and copulation duration in two populations of the polyandrousDrosophila serrata. Univariate analyses show little genetic variance in mating latency, and that males, but not females, contribute to copulation duration genetic variance. Further, multivariate analyses revealed little covariance between the studied traits. However, analyses considering male and female contribution in a single framework supported genetic contributions from both sexes for mating behaviours and complex patterns of between sexes correlations. Finally, our study did not find any association between those mating behaviours and fitness component, specifically (i) no phenotypic covariance between male attractiveness and mating latency and, (ii) longer copulations did not result in the production of more offspring. With no detectable fitness benefits in any sexes for shorter mating latency or longer copulation duration, our results do not support the presence of inter-nor intra-locus sexual conflict for these mating traits.
Biological traits and threats interact to drive extinctions in a simulation study
Authors: Chichorro Filipe , Correia Luís , Cardoso Pedro 
Published: October 2020

AbstractHow a particular threat influences extinction risk may depend on biological traits. Empirical studies relating threats and traits are needed, but data are scarce, making simulations useful. We implemented an eco-evolutionary model to analyse how five threat types influence the extinction risk of virtual organisms differing in body size, maturity age, fecundity, and dispersal ability. Results show that direct killing mostly affected slow-living and low dispersal organisms. Habitat loss and fragmentation both affected larger and less fecund organisms, but drove contrasting responses according to dispersal ability. Habitat degradation and the introduction of invasive competitors had similar effects, mostly affecting large, fast-living, and highly fecund organisms. Many of the reported results confirm previous studies, while others were never tested, creating new hypotheses for future empirical work.Statement of authorshipFC, LC and PC designed the study, FC implemented the model and ran the statistical analyses. FC and PC wrote the first draft, and all authors contributed substantially to further revisions.