bluuebunny/crossref_metadata_2025_split huggingface dataset:
A chromosome-level genome assembly of the woolly apple aphid,Eriosoma lanigerum(Hausmann) (Hemiptera: Aphididae)
Authors: Biello Roberto , Singh Archana , Godfrey Cindayniah J. , Fernández Fernández Felicidad , Mugford Sam T. , Powell Glen , Hogenhout Saskia A. , Mathers Thomas C. 
Published: May 2020

ABSTRACTWoolly apple aphid (WAA,Eriosoma lanigerumHausmann) (Hemiptera: Aphididae), is a major pest of apple trees (Malus domestica, order Rosales) and is critical to the economics of the apple industry in most parts of the world. Here, we generated a chromosome-level genome assembly of WAA – representing the first genome sequence from the aphid subfamily Eriosomatinae – using a combination of 10X Genomics linked-reads andin vivoHi-C data. The final genome assembly is 327 Mb, with 91% of the assembled sequences anchored into six chromosomes. The contig and scaffold N50 values are 158 kb and 71 Mb, respectively, and we predicted a total of 28,186 protein-coding genes. The assembly is highly complete, including 97% of conserved arthropod single-copy orthologues based on BUSCO analysis. Phylogenomic analysis of WAA and nine previously published aphid genomes, spanning four aphid tribes and three subfamilies, reveals that the tribe Eriosomatini (represented by WAA) is recovered as a sister group to Aphidini + Macrosiphini (subfamily Aphidinae). We identified syntenic blocks of genes between our WAA assembly and the genomes of other aphid species and find that two WAA chromosomes (El5 and El6) map to the conserved Macrosiphini and Aphidini X chromosome. Our high-quality WAA genome assembly and annotation provides a valuable resource for research in a broad range of areas such as comparative and population genomics, insect-plant interactions and pest resistance management.
A peptide-level multiple imputation strategy accounting for the different natures of missing values in proteomics data
Authors: Gianetto Q. Giai , Wieczorek S. , Couté Y. , Burger T. 
Published: May 2020

AbstractMotivationQuantitative mass spectrometry-based proteomics data are characterized by high rates of missing values, which may be of two kinds: missing completely-at-random (MCAR) and missing not-at-random (MNAR). Despite numerous imputation methods available in the literature, none account for this duality, for it would require to diagnose the missingness mechanism behind each missing value.ResultsA multiple imputation strategy is proposed by combining MCAR-devoted and MNAR-devoted imputation algorithms. First, we propose an estimator for the proportion of MCAR values and show it is asymptotically unbiased under assumptions adapted to label-free proteomics data. This allows us to estimate the number of MCAR values in each sample and to take into account the nature of missing values through an original multiple imputation method. We evaluate this approach on simulated data and shows it outperforms traditionally used imputation algorithms.AvailabilityThe proposed methods are implemented in the R package imp4p (available on the CRAN Giai Gianetto (2020)), which is itself accessible through Prostar software.Contactquentin.giaigianetto@pasteur.fr;thomas.burger@cea.fr
Natural variation in insect egg-induced cell death uncovers a role for L-type LECTIN RECEPTOR KINASE-I.1 in Arabidopsis
Authors: Groux Raphaël , Gouhier-Darimont Caroline , Kerdaffrec Envel , Reymond Philippe 
Published: May 2020

AbstractInArabidopsis thaliana, a hypersensitive-like response (HR-like) is triggered underneath the eggs of the large white butterflyPieris brassicae, and this response is dependent on salicylic acid (SA) accumulation and signaling. Previous reports indicate that the clade I L-type lectin receptor kinase LecRK-I.8 is involved in early steps of egg recognition. A genome-wide association study (GWAS) was used to better characterize the genetic structure of HR-like and discover loci that contribute to this response. We report here the identification of LecRK-I.1, a close homolog of LecRK-I.8, and show that two main haplotypes that explain part of the variation in HR-like segregate amongst natural Arabidopsis accessions. In addition, signatures of balancing selection at this locus suggest that it may be ecologically important. Disruption of LecRK-I.1 resulted in decreased HR-like and SA signaling, indicating that this protein is important for the observed responses. Furthermore, we provide evidence that LecRK-I.1 functions in the same signaling pathway as LecRK-I.8. Altogether, our results show that the response to eggs ofP. brassicaeis controlled by LecRKs that operate at various steps of the signaling pathway.
Development and on-site evaluation of an easy-to-perform and low-cost food pathogen diagnostic workflow for low-resource communities
Authors: Mason Michael Glenn , Botella José Ramón 
Published: May 2020

AbstractFood-borne diseases are a leading cause of illness and death in many developing countries and thus, there is a real need to develop affordable and practical technologies that can help improve food safety in these countries. The ability to efficiently identify food pathogens is essential to allow national regulatory authorities to monitor food quality and implement safety protocols. In this study, we have developed a simple, low-cost ($0.76 (USD)) complete food pathogen diagnostic workflow ideally suited for deployment in low-resource environments that uses a simple four step process (sample enrichment, cell lysis, DNA amplification, and naked-eye readout). The minimal number of steps and equipment involved in our diagnostic workflow, as well as the simplicity of the yes/no flocculation readout, allows non-technical personnel to perform and interpret the assay. To evaluate the system’s performance, we tested the entire system on fresh produce samples collected from local farms and markets in Cambodia for the presence of theE. coli O157O-antigen polymerase,wzy. Although this was a proof-of-concept study, our system successfully revealed a clear correlation between the origin and condition of the produce collected and their likelihood of contamination. In conclusion, we believe that our easy-to-perform diagnostic system can have a significant impact on improving food quality and human health if adopted by regulatory authorities in developing countries due to the assay’s simplicity, affordability, and adaptability.
AutoNeuriteJ: An ImageJ plugin for measurement and classification of neuritic extensions
Authors: Boulan Benoit , Beghin Anne , Ravanello Charlotte , Deloulme Jean-Christophe , Gory-Fauré Sylvie , Andrieux Annie , Brocard Jacques , Denarier Eric 
Published: May 2020

AbstractMorphometry characterization is an important procedure in describing neuronal cultures and identifying phenotypic differences. This task usually requires labor-intensive measurements and the classification of numerous neurites from large numbers of neurons in culture. To automate these measurements, we wrote AutoNeuriteJ, an imageJ/Fiji plugin that measures and classifies neurites from a very large number of neurons. We showed that AutoNeuriteJ is able to detect variations of neuritic growth induced by several compounds known to affect the neuronal growth. In these experiments measurement of more than 5000 mouse neurons per conditions was obtained within a few hours. Moreover, by analyzing mouse neurons deficient for the microtubule associated protein 6 (MAP6) and wild type neurons we illustrate that AutoNeuriteJ is capable to detect subtle phenotypic difference in axonal length. Overall the use of AutoNeuriteJ will provide rapid, unbiased and accurate measurement of neuron morphologies.
The postsynaptic MAGUK scaffold protein MPP2 organises a distinct interactome that incorporates GABAAreceptors at the periphery of excitatory synapses
Authors: Schmerl Bettina , Gimber Niclas , Kuropka Benno , Rentsch Jakob , Kunde Stella-Amrei , Ewers Helge , Freund Christian , Schmoranzer Jan , Rademacher Nils , Shoichet Sarah A. 
Published: May 2020

AbstractRecent advances in imaging technology have highlighted that scaffold proteins and receptors are arranged in sub-synaptic nanodomains. The synaptic MAGUK scaffold protein MPP2 is a component of AMPA receptor-associated protein complexes and also binds to the synaptic cell adhesion molecule SynCAM1. Using super-resolution imaging, we now show that MPP2 and SynCAM1 are situated at the periphery of the postsynaptic density. In order to explore MPP2-associated protein complexes, we used a quantitative comparative mass spectrometry approach and identified multiple GABAAreceptor subunits among the novel synaptic MPP2 interactors. We further show that GABAAreceptors are found together with MPP2 in a subset of dendritic spines and thus highlight MPP2 as a scaffold molecule capable of acting as an adaptor molecule that links peripheral synaptic elements critical for inhibitory regulation to central structures at the PSD of glutamatergic synapses.
TSPAN1 promotes human pancreatic cancer cells proliferation by modulating CDK1 via Akt
Authors: Wang Xin , Gao Xiaozhuo , Tian Jiaxun , Zhang Rui , Qiao Yun , Hua Xiangdong , Shi Gang 
Published: May 2020

AbstractBackgroundTo explore the potential therapeutic target to treat pancreatic cancers, Tspan1 was detected in human pancreatic cancer tissue and human pancreatic ductal adenocarcinoma cells and functional role of Tspan1 on proliferation was explored and the mechanism was investigated.Materials and MethodsTspan1 in PCC tissue and PDAC cell lines was measured by qRT-PCR and Western blot. Tspan1 was knock-downed and over-expressed in cells via transfection with Tspan1-siRNA and pLNCX-TSPAN1-cDNA, cell survival, proliferation and cell cycle were measured with MTT, Alamar blue and Flow Cytometry assay. The mRNA and protein expression were assessed by qRT-PCR and Western blotting. The expression of PI3K, Akt and p-Akt were detected, and CDK1 siRNA and specific inhibitor of Akt were used to explore the mechanism of TSPAN1 promoting PDAC cells proliferation.ResultsTspan1 expression in PCC tissue and PDAC cells was increased. Transfection of siRNA targeting Tspan1 in BxPC3 and PNAC-1 cells obviously decreased cell proliferation and down-regulated CDK1 expression. Consistently, both cell proliferation and CDK1 expression in BxPC3 and PNAC-1 cells were up-regulated with pLNCX-TSPAN1-cDNA transfection. Cell cycle analysis showed that after knockdown of Tspan1 the G2/M phase ratio was increased to cause mitosis arrest, and TSPAN1 overexpression caused cell cycle transition from G2 to M phase to promote cell proliferation. And these were dependent on the modulation of CDK1 expression via Akt.ConclusionTspan1 up-regulates CDK1 expression via activating Akt to promote human PCC cell proliferation and silencing of Tspan1 may be a potential therapeutic target to treat pancreatic cancers.
CD147 (BSG) but notACE2expression is detectable in vascular endothelial cells within single cell RNA sequencing datasets derived from multiple tissues in healthy individuals
Authors: Ganier C , Du-Harpur X , Harun N , Wan B , Arthurs C , Luscombe NM , Watt FM , Lynch MD 
Published: May 2020

ABSTRACTCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with a wide range of systemic manifestations. Several observations support a role for vascular endothelial dysfunction in the pathogenesis including an increased incidence of thrombotic events and coagulopathy and the presence of vascular risk factors as an independent predictor of poor prognosis. It has recently been reported that endothelitis is associated with viral inclusion bodies suggesting a direct role for SARS-CoV-2 in the pathogenesis. The ACE2 receptor has been shown to mediate SARS-CoV-2 uptake and it has been proposed that CD147 (BSG) can function as an alternative cell surface receptor. To define the endothelial cell populations that are susceptible to infection with SARS-CoV-2, we investigated the expression of ACE2 as well as other genes implicated in the cellular entry of SARS-Cov-2 in the vascular endothelium through the analysis of single cell sequencing data derived from multiple human tissues (skin, liver, kidney, lung and intestine). We found that CD147 (BSG) but notACE2is detectable in vascular endothelial cells within single cell sequencing datasets derived from multiple tissues in healthy individuals. This implies that eitherACE2is not expressed in healthy tissue but is instead induced in response to SARS-Cov2 or that SARS-Cov2 enters endothelial cells via an alternative receptor such as CD147.
A Heat-Shock Inducible System for Flexible Gene Expression in Cereals
Authors: Harrington Sophie A. , Backhaus Anna E. , Fox Samantha , Rogers Christian , Borrill Philippa , Uauy Cristobal , Richardson Annis 
Published: May 2020

AbstractBackgroundFunctional characterisation of genes using transgenic methods is increasingly common in cereal crops. Yet standard methods of gene over-expression can lead to undesirable developmental phenotypes, or even embryo lethality, due to ectopic gene expression. Inducible expression systems allow the study of such genes by preventing their expression until treatment with the specific inducer. When combined with the Cre-Lox recombination system, inducible promoters can be used to initiate constitutive expression of a gene of interest. Yet while these systems are well established in dicot model plants, likeArabidopsis thaliana, they have not yet been implemented in grasses.ResultsHere we present an irreversible heat-shock inducible system developed using Golden Gate-compatible components which utilises Cre recombinase to drive constitutive gene expression in barley and wheat. We show that a heat shock treatment of 38 °C is sufficient to activate the construct and drive expression of the gene of interest. Modulating the duration of heat shock controls the density of induced cells. Short durations of heat shock cause activation of the construct in isolated single cells, while longer durations lead to global construct activation. The system can be successfully activated in multiple tissues and at multiple developmental stages and shows no activation at standard growth temperatures (~ 20 °C).ConclusionsThis system provides an adaptable framework for use in gene functional characterisation in cereal crops. The developed vectors can be easily adapted for specific genes of interest within the Golden Gate cloning system. By using an environmental signal to induce activation of the construct, the system avoids pitfalls associated with consistent and complete application of chemical inducers. As with any inducible system, care must be taken to ensure that the expected construct activation has indeed taken place.
SCAN-ATAC-Sim: a scalable and efficient method for simulating single-cell ATAC-seq data from bulk-tissue experiments
Authors: Chen Zhanlin , Zhang Jing , Liu Jason , Zhang Zixuan , Zhu Jiangqi , Lee Donghoon , Xu Min , Gerstein Mark 
Published: May 2020

AbstractSummaryscATAC-seq is a powerful approach for characterizing cell-type-specific regulatory landscapes. However, it is difficult to benchmark the performance of various scATAC-seq analysis techniques (such as clustering and deconvolution) without havinga prioria known set of gold-standard cell types. To simulate scATAC-seq experiments with known cell-type labels, we introduce an efficient and scalable scATAC-seq simulation method (SCAN-ATAC-Sim) that down-samples bulk ATAC-seq data (e.g., from representative cell lines or tissues). Our protocol uses a consistent but tunable signal-to-noise ratio across cell types in a scATAC-seq simulation for integrating bulk experiments with different levels of background noise, and it independently samples twice without replacement to account for the diploid genome. Because it uses an efficient weighted reservoir sampling algorithm and is highly parallelizable with OpenMP, our implementation in C++ allows millions of cells to be simulated in less than an hour on a laptop computer.AvailabilitySCAN-ATAC-Sim is available atscan-atac-sim.gersteinlab.org.Contactpi@gersteinlab.orgSupplementary informationSupplementary data are available atBioinformaticsonline.
Identification and analysis of splicing quantitative trait loci across multiple tissues in the human genome
Authors: Garrido-Martín Diego , Borsari Beatrice , Calvo Miquel , Reverter Ferran , Guigó Roderic 
Published: May 2020

AbstractWe have developed an efficient and reproducible pipeline for the discovery of genetic variants affecting splicing (sQTLs), based on an approach that captures the intrinsically multivariate nature of this phenomenon. We employed it to analyze the multi-tissue transcriptome GTEx dataset, generating a comprehensive catalogue of sQTLs in the human genome. A core set of these sQTLs is shared across multiple tissues. Downstream analyses of this catalogue contribute to the understanding of the mechanisms underlying splicing regulation. We found that sQTLs often target the global splicing pattern of genes, rather than individual splicing events. Many of them also affect gene expression, but not always of the same gene, potentially uncovering regulatory loci that act on different genes through different mechanisms. sQTLs tend to be preferentially located in introns that are post-transcriptionally spliced, which would act as hotspots for splicing regulation. While many variants affect splicing patterns by directly altering the sequence of splice sites, many more modify the binding of RNA-binding proteins (RBPs) to target sequences within the transcripts. Genetic variants affecting splicing can have a phenotypic impact comparable or even stronger than variants affecting expression, with those that alter RBP binding playing a prominent role in disease.
Effects of Post-Myocardial Infarction Heart Failure on the Bone Vascular Niche
Authors: Hoffmann Jedrzej , Luxán Guillermo , Abplanalp Wesley Tyler , Glaser Simone-Franziska , Rasper Tina , Fischer Ariane , Muhly-Reinholz Marion , John David , Assmus Birgit , Zeiher Andreas Michael , Dimmeler Stefanie 
Published: May 2020

SummaryBone vasculature provides protection and signals necessary to control stem cell quiescence and renewal1. Specifically, type H capillaries, which highly express Endomucin, constitute the endothelial niche supporting a microenvironment of osteoprogenitors and long-term hematopoietic stem cells2–4. The age-dependent decline in type H endothelial cells was shown to be associated with bone dysregulation and accumulation of hematopoietic stem cells, which display cell-intrinsic alterations and reduced functionality3. The regulation of bone vasculature by chronic diseases, such as heart failure is unknown. Here, we describe the effects of myocardial infarction and post-infarction heart failure on the vascular bone cell composition. We demonstrate an age-independent loss of type H bone endothelium in heart failure after myocardial infarction in both mice and in humans. Using single-cell RNA sequencing, we delineate the transcriptional heterogeneity of human bone marrow endothelium showing increased expression of inflammatory genes, includingIL1BandMYC, in ischemic heart failure. Inhibition of NLRP3-dependent IL-1β production partially prevents the post-myocardial infarction loss of type H vasculature in mice. These results provide a rationale for using anti-inflammatory therapies to prevent or reverse the deterioration of vascular bone function in ischemic heart disease.
ATM Inhibition Synergizes with Fenofibrate in High Grade Serous Ovarian Cancer Cells
Authors: Chen Chi-Wei , Buj Raquel , Dahl Erika S. , Leon Kelly E. , Aird Katherine M. 
Published: May 2020

AbstractBackgroundEpithelial ovarian cancer (EOC) is the deadliest gynecological malignancy in the United States with high grade serous ovarian cancer (HGSOC) as the most commonly diagnosed subtype. While therapies targeting deficiencies in the homologous recombination (HR) pathway are emerging as the standard treatment for HGSOC patients, this strategy is limited to the 50% of patients with a deficiency in this pathway. Therefore, patients with HR-proficient tumors are likely to be resistant to these therapies and require alternative strategies.MethodsData from HGSOC patients in The Cancer Genome Atlas (TCGA) were analyzed for ATM status, ATM and PPARα expression, and used to perform Gene Set Enrichment Analysis (GSEA). Screening data from the Dependency Map were analyzed to identify FDA-approved drugs that preferentially inhibit ATM-low cancer cells.In vitrostudies were performed to determine whether ATM inhibitors synergize with the PPARα agonist fenofibrate in HGSOC cell lines.ResultsThe HR gene Ataxia Telangiectasia Mutated (ATM) is wildtype in the majority of HGSOC patients and its kinase activity is upregulated compared to normal fallopian tube tissue. As high ATM has been associated with poor overall and progression-free survival, targeting ATM may be beneficial for a subset of HGSOC patients. Clinical trials of ATM inhibitors are commencing; however, ATM inhibitors are not effective as single agents. We aimed to explore novel therapeutic vulnerabilities of ATM deficient cells to develop a combinatorial therapy. Using data from TCGA, we found that multiple pathways related to metabolism are inversely correlated with ATM expression, suggesting that combining ATM inhibition and metabolic inhibition would be effective. Indeed, analysis of FDA-approved drugs from the Dependency Map demonstrated that ATM low cell lines are more sensitive to fenofibrate, a PPARα agonist that has been previously shown to affect multiple cellular metabolic pathways. Consistently, PPARα signaling is associated with ATM expression. We validated that combined inhibition of ATM and treatment with fenofibrate is synergistic in multiple HGSOC cell lines by inducing senescence.ConclusionsOur results suggest that metabolic changes induced by ATM inhibitors are a potential target for the treatment for HGSOC.