bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cumulative effects of social stress on reward-guided actions and prefrontal cortical activity
Authors: Barthas Florent , Hu Melody Y. , Siniscalchi Michael J. , Ali Farhan , Mineur Yann S. , Picciotto Marina R. , Kwan Alex C. 
Published: October 2019

AbstractWhen exposed to chronic social stress, animals display behavioral changes that are relevant to depressive-like phenotypes. However, the cascading relationship between incremental stress exposure and neural dysfunctions over time remains incompletely understood. Here we characterize the longitudinal effect of social defeat on goal-directed actions and prefrontal cortical activity in mice, using a head-fixed sucrose preference task and two-photon calcium imaging. Behaviorally, stress-induced loss of reward sensitivity intensifies over days. Motivational anhedonia, the failure to translate positive reinforcements into future actions, requires multiple sessions of stress exposure to become fully established. For neural activity, individual layer 2/3 pyramidal neurons in the Cg1 and M2 subregions of the medial prefrontal cortex have heterogeneous responses to stress. Changes in ensemble activity differ significantly between susceptible and resilient animals after the first defeat session, and continue to diverge following successive stress episodes before reaching persistent abnormal levels. Collectively, these results demonstrate that the cumulative impact of an ethologically relevant stress can be observed at the level of cellular activity of individual prefrontal neurons. The distinct neural responses associated with resilience versus susceptibility raises the hypothesis that the negative impact of social stress is neutralized in resilient animals, in part through an adaptive reorganization of prefrontal cortical activity.
Single-cell RNA counting at allele- and isoform-resolution using Smart-seq3
Authors: Hagemann-Jensen Michael , Ziegenhain Christoph , Chen Ping , Ramsköld Daniel , Hendriks Gert-Jan , Larsson Anton J.M. , Faridani Omid R. , Sandberg Rickard 
Published: October 2019

AbstractLarge-scale sequencing of RNAs from individual cells can reveal patterns of gene, isoform and allelic expression across cell types and states1. However, current single-cell RNA-sequencing (scRNA-seq) methods have limited ability to count RNAs at allele- and isoform resolution, and long-read sequencing techniques lack the depth required for large-scale applications across cells2,3. Here, we introduce Smart-seq3 that combines full-length transcriptome coverage with a 5’ unique molecular identifier (UMI) RNA counting strategy that enabled in silico reconstruction of thousands of RNA molecules per cell. Importantly, a large portion of counted and reconstructed RNA molecules could be directly assigned to specific isoforms and allelic origin, and we identified significant transcript isoform regulation in mouse strains and human cell types. Moreover, Smart-seq3 showed a dramatic increase in sensitivity and typically detected thousands more genes per cell than Smart-seq2. Altogether, we developed a short-read sequencing strategy for single-cell RNA counting at isoform and allele-resolution applicable to large-scale characterization of cell types and states across tissues and organisms.
Genetic diversity and taxonomic issues inGastridiumP.Beauv (Poaceae) inferred from plastid and nuclear DNA sequence analysis
Authors: Scoppola Anna , Cardoni Simone , Pellegrino Mariangela , López-Tirado Javier , Simeone Marco Cosimo 
Published: October 2019

AbstractIncomplete taxonomic knowledge may seriously hamper biodiversity conservation efforts that are crucial in a context of global change.GastridiumP.Beauv. is a Mediterranean-Paleotropical member of the Poaceae family, inhabiting ephemeral grass habitats, whose species number and diversity are still imperfectly known. In order to progress towards a comprehensive taxonomic treatment of this genus, we examined patterns of DNA diversity in the four taxa (Gastridium lainzii,G. phleoides,G. scabrum, andG. ventricosum) that have been recently advanced by different authors, based on new morpho-ecological descriptors. We explored nucleotide sequence variation at two plastid (trnH-psbA, trnL-F) and one nuclear (ITS) DNA markers in 44 total individuals. Diversity data were treated with multiple statistical and phylogenetic tools, and integrated with available GenBank sequences ofGastridiumand other closely related genera. Despite the limited variability detected, evidence of within-taxon genetic cohesion and estimates of molecular divergence comparable with those of species in the same subtribal lineage (Agrostidinae) were recovered. The identified plastid genealogies appeared congruent with a subdivision of the genus into (at least) three distinct entities, and coherent with collected morphological descriptors. Phylogenetic reconstructions with ITS were less corresponding to taxa identities, likely due to reticulation and polyploidization. Once placed in a broader taxonomic context, the investigated dataset produced plastid and nuclear tree topologies consistent with previous assessments, highlighting the overall little resolution of species and genera within Agrostidinae. In the plastid tree, a sister relationship betweenGastridiumandTriplachnewas weakly supported. In the ITS tree, relationships among these genera were unresolved. The hypothesis of closely related but separately evolving lineages withinGastridiumis discussed, suggesting a re-evaluation of its current assessment in taxonomic authorities to enhance our knowledge of the grass family, and assist future biodiversity surveys of key Mediterranean grassland ecosystems.
A comprehensive human minimal gut metagenome extends the host’s metabolic potential
Authors: Parras-Moltó Marcos , Aguirre de Cárcer Daniel 
Published: October 2019

ABSTRACTAccumulating evidence suggests that humans should be considered as holobionts in which the gut microbiota plays essential functions. Initial metagenomic studies reported a pattern of shared genes in the gut microbiome of different individuals, leading to the definition of the minimal gut metagenome as the set of microbial genes necessary for homeostasis, and present in all healthy individuals. Despite its interest, this concept has received little attention following its initial description in terms of various ubiquitous pathways in Western cohorts. This study analyzes the minimal gut metagenome of the most comprehensive dataset available, including individuals from agriculturalist and industrialist societies, also embodying highly diverse ethnic and geographical backgrounds. The outcome, based on metagenomic predictions for community composition data, resulted in a minimal metagenome comprising 3,412 gene clusters, mapping to 1,856 reactions and 128 metabolic pathways predicted to occur across all individuals. These results were substantiated by the analysis of two additional datasets describing the microbial community compositions of larger Western cohorts, as well as a substantial shotgun metagenomics dataset. Subsequent analyses showed the plausible metabolic complementarity provided by the minimal gut metagenome to the human genome.
Genome-wide identification of accessible chromatin regions in bumblebee (Bombus terrestris) by ATAC-seq
Authors: Zhao Xiaomeng , Xu Weilin , Schaack Sarah , Sun Cheng 
Published: October 2019

AbstractBumblebees (Hymenoptera: Apidae) are important pollinating insects that play pivotal roles in crop production and natural ecosystem services. To date, while the protein-coding sequences of bumblebees have been extensively annotated, regulatory elements, such as promoters and enhancers, have been poorly annotated in the bumblebee genome. To achieve a comprehensive profile of accessible chromatin regions and provide clues for all possible regulatory elements in the bumblebee genome, we did ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) for B. terrestris samples derived from its four developmental stages: egg, larva, pupa, and adult, respectively. The sequencing reads of ATAC-seq were mapped to B. terrestris reference genome, and the accessible chromatin regions of bumblebee were identified and characterized by using bioinformatic methods. Our study will provide important resources not only for uncovering regulatory elements in the bumblebee genome, but also for expanding our understanding of bumblebee biology. The ATAC-seq data generated in this study has been deposited in NCBI GEO (accession#: GSE131063).
Glutathione Peroxidase 8 (GPX8)-IL6 axis is essential in maintaining breast cancer mesenchymal stem-like state and aggressive phenotype
Authors: Khatib Anees , Balakrishnan Solaimuthu , Ben-Yosef Michal , Oren Gidi , Abu Rmaileh Areej , Schlesinger Michal , Axelrod Jonathan H. , Lichtenstein Michal , Shaul Yoav D. 
Published: October 2019

AbstractMetabolic reprogramming as a downstream result of oncogenic signaling pathways has been described as a hallmark of cancer. Here, we describe a reverse scenario in which a metabolic enzyme regulates cancer cell behavior by triggering a signaling pathway. We find that glutathione peroxidase 8 (GPX8), a poorly characterized redox enzyme that resides in the endoplasmic reticulum, is upregulated during the epithelial-to-mesenchymal (EMT) program in HMLE and A549 cells. In cancer patients, high tumor levels of GPX8 correlate with mesenchymal markers and poor patient outcome. Strikingly, GPX8 knockout in mesenchymal-like cells results in an epithelial-like morphology, downregulation of EMT characteristics, loss of cancer stemness features, and impeded tumor initiation in mice. We determine the mechanism governing this reduction in cancer aggressiveness is through the repression of crucial autocrine factors, in particular, interleukin-6 (IL-6). Specifically, GPX8 knockout impairs IL-6-driven activation of the JAK-STAT3 signaling pathway, a critical regulator of a cancer-aggressive state. Altogether, we uncover the GPX8-IL-6 axis as a novel metabolic-inflammatory pathway that acts as a robust EMT activator and program to induce aggressive cancer cell characteristics.
Single-cell dissection of a rare human prostate basal cell carcinoma
Authors: Su Xianbin , Long Qi , Bo Juanjie , Shi Yi , Zhao Li-Nan , Lin Yingxin , Luo Qing , Ghazanfar Shila , Zhang Chao , Liu Qiang , Wang Lan , He Kun-Yan , He Jian , Cui Xiao-Fang , Yang Jean Y. H. , Han Ze-Guang , Sha Jian-Jun , Yang Guoliang 
Published: October 2019

AbstractAs a rare subtype of prostate carcinoma, basal cell carcinoma (BCC) has not been studied extensively and thus lacks systematic molecular characterization. Here we applied single-cell genomic amplification and RNA-Seq to a specimen of human prostate BCC (CK34βE12+/P63+/PAP−/PSA−). The mutational landscape was obtained via whole exome sequencing of the amplification mixture of 49 single cells, and the 5 putative driver genes mutated areCASC5,NUTM1,PTPRC,KMT2CandTBX3. The top 3 nucleotide substitutions are C>T, T>C and C>A, similar to common prostate cancer. The distribution of the variant allele frequency values indicated these single cells are from the same tumor clone. The transcriptomes of 69 single cells were obtained, and they were clustered into tumor, stromal and immune cells based on their global transcriptomic profiles. The tumor cells specifically express basal cell markers likeKRT5,KRT14andKRT23, and epithelial markersEPCAM,CDH1andCD24. The transcription factor (TF) co-variance network analysis showed that the BCC tumor cells have distinct regulatory networks. By comparison with current prostate cancer datasets, we found that some of the bulk samples exhibit basal-cell signatures. Interestingly, at single-cell resolution the gene expression patterns of prostate BCC tumor cells show uniqueness compared with that of common prostate cancer-derived circulating tumor cells. This study, for the first time, discloses the comprehensive mutational and transcriptomic landscapes of prostate BCC, which lays a foundation for the understanding of its tumorigenesis mechanism and provides new insights into prostate cancers in general.
Synthesis and Characterisation of Aqueous Haemoglobin-based Microcapsules Coated by Genipin-Cross-Linked Albumin
Authors: Schakowski Kai Melvin , Linders Jürgen , Ferenz Katja Bettina , Kirsch Michael 
Published: October 2019

AbstractBovine serum albumin (BSA)-coated haemoglobin (Hb)-microcapsules prepared by co-precipitation of Hb and MnCO3may present an alternative type of artificial blood substitute. Prepared microcapsules were analysed by Scanning electron microscopy (SEM) and Respirometry, cytotoxicity was evaluated by addition of microcapsules to murine fibroblast-derived cell line L929 (American Type Culture Collection, NCTC clone 929 of strain L). The capsules come along with a mean diameter of approximately 0.6 μm and a mean volume of 1.13 ∙ 10−19L, thus an average human red blood cell with a volume of 9 ∙ 10−14L is about 800,000 times bigger. Hb-microcapsules are fully regenerable by ascorbic acid and maintain oxygen affinity because oxygen is able to pass the BSA wall of the capsules and thereby binding to the ferrous iron of the haemoglobin entity. Therefore, these microcapsules present a suitable type of potential artificial haemoglobin-based oxygen carrier (HbOC).
The Toxin Cercosporin is a Virulence Factor for Infection of Coffee byCercospora coffeicola
Authors: Souza A. G. C. , Herrero S. , Daub M. E. 
Published: October 2019

ABSTRACTBrown eye spot, caused byCercospora coffeicola, causes significant losses in both quality and quantity of coffee production. As manyCercosporaspp. produce the photoactivated toxin cercosporin, this study aimed to determine the role of cercosporin inC. coffeicolapathogenesis by creating disruption mutants unable to produce the toxin. SixC. coffeicolaisolates from Brazilian fields, representing organic and conventional production systems in the Minas Gerais state, were evaluated for their ability to produce cercosporinin vitro. Toxin production varied among isolates, ranging from 3.5 – 25.3 µM/ 5 mm mycelial plug; production was undetectable in one isolate. TheC. coffeicolahomolog of the polyketide synthase gene (CTB1) involved in cercosporin production was amplified using a degenerate primer strategy. The 7044 ntccCTB1gene sequence was 90.3% identical to thecnCTB1gene inCercospora nicotianaeand encoded a putative protein of 2196 amino acids with 98.2% similarity and 97.5% identity to its counterpart inC. nicotianae. Transformation of two isolates ofC. coffeicolawith aCTB1disruption construct resulted in the recovery of sixctb1disruption mutants. All of thectb1disruptants were deficient in cercosporin production. Disruption mutants did not differ significantly from the wild type for either growth or sporulation, but were significantly altered in virulence on coffee. As compared to wild type, time to lesion development was significantly increased and numbers of lesions were significantly decreased in coffee plants inoculated withctb1disruption mutants. These results show that cercosporin toxin is a virulence factor forC. coffeicolainfection of coffee.
Machine Learning Approaches Identify Genes Containing Spatial Information from Single-Cell Transcriptomics Data
Authors: Loher Phillipe , Karathanasis Nestoras 
Published: October 2019

AbstractMotivationWe participated in the DREAM Single Cell Transcriptomics Challenge. The challenge’s focus was two-fold; a) to identify the top 60, 40 and 20 genes that contain the most spatial information, and b) to reconstruct the 3-D arrangement of the D. melanogaster embryo using information from those genes.ResultsWe developed two independent approaches, leveraging machine learning models from Lasso and Deep Neural Networks, that we successfully apply to high-dimensional single-cell sequencing data. Our methods allowed us to achieve top performance when compared to the ground truth. Among ~40 participating teams, the resulting solutions placed 10th, 6th, and 4th in the three DREAM sub-challenges #1, #2 and #3, respectively. Notably, for the Lasso approach we introduced a feature selection technique, Lasso-TopX, that allows a user to define a specific number of features they are interested in and the Neural Network approach utilizes weak supervision for linear regression to accommodate for uncertain or probabilistic training labels. Furthermore, we identified novel D. melanogaster genes that carry important positional information and were not previously suspected. Lastly, we show how the indirect use of the full datasets’ information can lead to data leakage and generate bias in overestimating the model’s performance.Availabilityhttps://github.com/TJU-CMC-Org/SingleCell-DREAM/.ContactNestoras.Karathanasis@jefferson.edu
Neural representation of bat predation risk and evasive flight in moths: a modelling approach
Authors: Goerlitz Holger R. , ter Hofstede Hannah M. , Holderied Marc W. 
Published: October 2019

AbstractMost animals are at risk from multiple predators and can vary anti-predator behaviour based on the level of threat posed by each predator. Animals use sensory systems to detect predator cues, but the relationship between the tuning of sensory systems and the sensory cues related to predator threat are not well-studied at the community level. Noctuid moths have ultrasound-sensitive ears to detect the echolocation calls of predatory bats. Here, combining empirical data and mathematical modelling, we show that moth hearing is adapted to provide information about the threat posed by different sympatric bat species. First, we found that multiple characteristics related to the threat posed by bats to moths correlate with bat echolocation call frequency. Second, the frequency tuning of the most sensitive auditory receptor in noctuid moth ears provides information allowing moths to escape detection by all sympatric bats with similar safety margin distances. Third, the least sensitive auditory receptor usually responds to bat echolocation calls at a similar distance across all moth species for a given bat species. If this neuron triggers last-ditch evasive flight, it suggests that there is an ideal reaction distance for each bat species, regardless of moth size. This study shows that even a very simple sensory system can adapt to deliver information suitable for triggering appropriate defensive reactions to each predator in a multiple predator community.
Detection and discrimination of influenza B Victoria lineage deletion variant viruses by real-time RT-PCR
Authors: Shu Bo , Kirby Marie K. , Warnes Christine , Sessions Wendy M. , Davis William G. , Liu Ji , Wilson Malania M. , Wentworth David E. , Barnes John R. 
Published: October 2019

ABSTRACTInfluenza B viruses have two genetically and antigenically distinct lineages, B/Victoria/2/1987-like (VIC) and B/Yamagata/16/1988-like (YAM) viruses, that emerged in the 1980s and co-circulate annually during the influenza season. During the 2016-2017 influenza season, influenza B/VIC lineage variant viruses emerged with two (K162N163) or three (K162N163D164) amino acid (AA) deletions in the hemagglutinin protein. Hemagglutination inhibition assays demonstrate that these deletion variant influenza B/VIC viruses are antigenically distinct from each other and from the progenitor B/VIC virus that lacks the deletion. Therefore, there are currently four antigenically distinct HA proteins expressed by influenza B co-circulating: B/YAM, B/VIC V1A (no deletion), B/VIC V1A.1 (two-AA deletion), and B/VIC V1A.2 and V1A.3 (three-AA deletion). The prevalence of these viruses differs across geographic regions, making it critical to have a sensitive, rapid diagnostic assay(s) that detect and distinguish these Influenza B variant viruses during surveillance. Here, we present a real time RT-PCR assay that targets the influenza B/VIC deletion region in the HA gene and detects and distinguishes the influenza B/VIC V1A, B/VIC V1A.1, B/VIC V1A.2 and B/VIC V1A.3 variant viruses, with no cross-reactivity. This assay can be run as a multiplex reaction, allowing for increased testing efficiency and reduced cost. Coupling this assay with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel Influenza B Lineage Genotyping Kit results in rapid detection and characterization of circulating influenza B viruses. Having accurate and detailed surveillance information on these distinct Influenza B variant viruses will provide insight into the prevalence and geographic distribution and could aid in vaccine recommendations.
A theophylline-responsive riboswitch regulates expression of nuclear-encoded genes in Arabidopsis
Authors: Shanidze Nana , Lenkeit Felina , Hartig Jörg S. , Funck Dietmar 
Published: October 2019

ABSTRACTLigand-responsive synthetic riboswitches are versatile and innovative tools for external gene regulation in pro- and eukaryotes. Riboswitches are smallcis-regulatory RNA elements that regulate gene expression by conformational changes in response to ligand binding. In plants, synthetic riboswitches were used to regulate gene expression in plastids, but the application of synthetic riboswitches for the regulation of nuclear-encoded genesin plantahas not been reported so far. Here we characterize the properties of a theophylline-responsive synthetic aptazyme for control of nuclear-encoded transgenes in Arabidopsis (Arabidopsis thaliana). Activation of the aptazyme, inserted in the 3-UTR of the target gene, resulted in rapid self-cleavage and subsequent decay of the mRNA. This riboswitch allowed reversible, theophylline-dependent downregulation of theGreen Fluorescent Protein(GFP) reporter gene in a dose- and time- dependent manner. Insertion of the riboswitch into theOne Helix Protein 1(OHP1) gene allowed complementation ofohp1mutants and induction of the mutant phenotype by theophylline.GFPorOHP1transcript levels were downregulated by maximally 90%, and GFP protein levels by 95%. These results establish artificial riboswitches as tools for externally controlled gene expression in synthetic biology in plants or functional crop design.One sentence summaryArtificial, ligand-responsive RNA aptazymes are an efficient tool for dose- and time-dependent external control of nuclear gene expression in plants.
Genome assembly of the common pheasantPhasianus colchicus, a model for speciation and ecological genomics
Authors: Liu Yang , Liu Simin , Zhang Nan , Chen De , Que Pinjia , Liu Naijia , Höglund Jacob , Zhang Zhengwang , Wang Biao 
Published: October 2019

AbstractThe common pheasant (Phasianus colchicus) in the order Galliformes and the family Phasianidae, has 30 subspecies distributed across its native range in the Palearctic realm and has been introduced to Europe, North America, and Australia. It is an important game bird often subjected to wildlife management as well as a model species to study speciation, biogeography and local adaptation. However, the genomic resources for the common pheasant are generally lacking. We sequenced a male individual of the subspeciestorquatusof the common pheasant with the Illumina Hiseq platform. We obtained 94.88 Gb of usable sequences by filtering out low-quality reads of the raw data generated. This resulted in a 1.02 Gb final assembly, which equals the estimated genome size. BUSCO analysis using chicken as a model showed that 93.3% of genes were complete. The contig N50 and scaffold N50 sizes were 178 kb and 10.2 Mb, respectively. All these indicate that we obtained a high-quality genome assembly. We annotated 16,485 protein-coding genes and 123.3 Mb (12.05 % of the genome) of repetitive sequences by ab initio and homology-based prediction. Furthermore, we applied a RAD-sequencing approach for another 45 individuals of seven representative subspecies in China and identified 4,376,351 novel single nucleotide polymorphism (SNPs) markers. Using this unprecedented dataset, we uncover the geographic population structure and genetic introgression among common pheasants in China. Our results provide the first high-quality reference genome for the common pheasant and a valuable genome-wide SNP database for studying population genomics and demographic history.