bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome profile and clinical characterization of ICOS expression in brain gliomas
Authors: Wang Jin , Shi Fei , Shan Aijun 
Published: May 2022

ABSTRACTAimsInducible Co-Stimulator (ICOS), an immune costimulatory molecule, has been found to play an essential role across various malignancies. This study investigated the transcriptome profile and clinical characterization of ICOS in gliomas.MethodsClinical information and transcriptome data of 301 glioma samples were downloaded from the Chinese Glioma Genome Atlas (CGGA) data set for analysis. Furthermore, the results were validated in 697 samples with RNAseq data from the TCGA glioma data set. In addition, single-cell sequencing data from CGGA and GSE 163108 datasets were used to analyze the ICOS expression across different cell types. Statistical analyses and figure production were performed with R-language.ResultsWe found that ICOS was significantly upregulated in higher-grade, IDH wildtype, and mesenchymal subtype of gliomas. Functional enrichment analyses revealed that ICOS was mainly involved in glioma-related immune response. Moreover, ICOS showed a robust correlation with other immune checkpoints, including PD1/PD-L1/PD-L2 pathway, CTLA4, ICOSL (ICOS ligand), and IDO1. Furthermore, based on seven clusters of metagenes, GSVA identified that ICOS was tightly associated with HCK, LCK, MHC-I, MHC-II, STAT1, and interferon, especially with LCK, suggesting a strong correlation between ICOS and T-cell activity in gliomas. In cell lineage analysis, ICOS-higher gliomas tended to recruit dendritic cells, monocytes, and macrophages into the tumor microenvironment. Single-cell sequencing analysis indicated that ICOS was highly expressed by regulatory T cells (Treg). Finally, patients with higher ICOS had shortened survival. ICOS was an independent prognosticator for glioma patients.ConclusionsHigher ICOS was correlated with more malignancy of gliomas and significantly associated with Treg activity among glioma-related immune responses. Moreover, ICOS could contribute as an independent prognostic factor for gliomas. Our study highlighted the role of ICOS in glioma and may facilitate therapeutic strategies targeting ICOS for glioma.
Eulertigs: minimum plain text representation of k-mer sets without repetitions in linear time
Authors: Schmidt Sebastian , Alanko Jarno N. 
Published: May 2022

AbstractA fundamental operation in computational genomics is to reduce the input sequences to their constituent k-mers. For maximum performance of downstream applications it is important to store the k-mers in small space, while keeping the representation easy and efficient to use (i.e. without k-mer repetitions and in plain text). Recently, heuristics were presented to compute a near-minimum such representation. We present an algorithm to compute a minimum representation in optimal (linear) time and use it to evaluate the existing heuristics. For that, we present a formalisation of arc-centric bidirected de Bruijn graphs and carefully prove that it accurately models the k-mer spectrum of the input. Our algorithm first constructs the de Bruijn graph in linear time in the length of the input strings (for a fixed-size alphabet). Then it uses a Eulerian-cycle-based algorithm to compute the minimum representation, in time linear in the size of the output.2012 ACM Subject ClassificationApplied computing → Computational biology; Theory of computation → Data compression; Theory of computation → Graph algorithms analysis; Theory of computation → Data structures design and analysis
Cerebellar Bergmann Glia Integrating Noxious Information Modulate Nocifensive Behaviors
Authors: Kim Seung Ha , Lee Jaegeon , Roh Seung-Eon , Jang Mirae , Kim Soobin , Lee Ji Hwan , Seo Jewoo , Hwang Jae Yoon , Lee Yong-Seok , Shigetomi Eiji , Lee C. Justin , Koizumi Schuichi , Kim Sun Kwang , Kim Sang Jeong 
Published: May 2022

AbstractClinical studies have revealed that the cerebellum is activated by noxious stimuli or pathological pain, and its removal results in somatosensory dysfunction. However, the neural circuits and molecular mechanisms underlying the processing of noxious information in the cerebellum remain unknown. Using two-photon microscopy and optogenetics in mice, we found that the locus coeruleus (LC) terminals in the cerebellar cortex release noradrenaline (NA) in response to cutaneous noxious electrical stimuli. Most Bergmann glia (BG) accumulated this LC-NA noxious information by increasing intracellular calcium in an integrative manner. This global calcium activation of BG, referred to as “flare,” was also elicited in response to an intraplantar capsaicin injection. Chemogenetic inactivation of LC terminals or BG in the cerebellar cortex suppressed BG flares and reduced licking, a nocifensive behavior associated with capsaicin-induced pain. BG-specific knockdown of α-1 adrenergic receptors also suppressed capsaicin-induced BG flares and licking. Chemogenetic activation of BG or an intraplantar capsaicin injection reduced Purkinje cell firings, which disinhibited the output activity of the deep cerebellar nuclei. These results suggest that BG in the cerebellar cortex play an essential role in computing noxious information ascending from the LC and modulate pain-related behaviors by controlling the activity of the cerebellar neural circuits.One Sentence SummaryBergmann glia mediate noxious information processing in the cerebellum
Guided construction of single cell reference for human and mouse lung
Authors: Guo Minzhe , Morley Michael P. , Wu Yixin , Du Yina , Zhao Shuyang , Wagner Andrew , Kouril Michal , Jin Kang , Gaddis Nathan , Kitzmiller Joseph A. , Stewart Kathleen , Basil Maria C. , Lin Susan M. , Ying Yun , Babu Apoorva , Wikenheiser-Brokamp Kathryn A. , Mun Kyu Shik , Naren Anjaparavanda P. , Lin Sara , Clair Geremy , Adkins Joshua N. , Pryhuber Gloria S. , Misra Ravi S. , Aronow Bruce J. , Tickle Timothy L. , Salomonis Nathan , Sun Xin , Morrisey Edward E. , Whitsett Jeffrey A. , Xu Yan ,   NHLBI LungMAP Consortium
Published: May 2022

ABSTRACTAccurate cell type identification is a key and rate-limiting step in single cell data analysis. Single cell references with comprehensive cell types, reproducible and functional validated cell identities, and common nomenclatures are much needed by the research community to optimize automated cell type annotation and facilitate data integration, sharing, and collaboration. In the present study, we developed a novel computational pipeline to utilize the LungMAP CellCards as a dictionary to consolidate single-cell transcriptomic datasets of 104 human lungs and 17 mouse lung samples and constructed “LungMAP CellRef” and “LungMAP CellRef Seed” for both normal human and mouse lungs. “CellRef Seed” has an equivalent prediction power and produces consistent cell annotation as does “CellRef” but improves computational efficiency and simplifies its utilization for fast automated cell type annotation and online visualization. This atlas set incorporates 48 human and 40 mouse well-defined lung cell types catalogued from diverse anatomic locations and developmental time points. Using independent datasets, we demonstrated the utility of our CellRefs for automated cell type annotation analysis of both normal and disease lungs. User-friendly web interfaces were developed to support easy access and maximal utilization of the LungMAP CellRefs. LungMAP CellRefs are freely available to the pulmonary research community through fast interactive web interfaces to facilitate hypothesis generation, research discovery, and identification of cell type alterations in disease conditions.
Borg tandem repeats undergo rapid evolution and are under strong selection to create new intrinsically disordered regions in proteins
Authors: Schoelmerich Marie C. , Sachdeva Rohan , Waldburger Lucas , West-Roberts Jacob , Banfield Jillian F. 
Published: May 2022

AbstractBorgs are huge, linear extrachromosomal elements associated with anaerobic methane-oxidizing archaea. Striking features of Borg genomes are pervasive tandem direct repeat (TR) regions. Here, we present six new Borg genomes and investigate the characteristics of tandem repeats in all ten complete Borg genomes. We find that TR regions are rapidly evolving, recently formed, arise independently and are virtually absent in hostMethanoperedensgenomes. Flanking partial repeats and A-enriched character constrain the TR formation mechanism. TRs can be in intergenic regions, where they might serve as regulatory RNAs, or in open reading frames (ORFs). TRs in ORFs are under very strong selective pressure, leading to perfect amino acid TRs (aaTRs) that are commonly intrinsically disordered regions. Proteins with aaTRs are often extracellular or membrane proteins, and functionally similar or homologous proteins often have aaTRs composed of the same amino acids. We propose that Borg aaTR-proteins functionally diversifyMethanoperedensand all TRs are crucial for specific Borg-host associations and possibly co-speciation.
3D flightpaths reveal the development of spatial memory in wild hummingbirds
Authors: Pritchard David J. , Hurly T. Andrew , Photopoulou Theoni , Healy Susan D. 
Published: May 2022

ABSTRACTMany animals learn to relocate important places and reflect this spatial knowledge in their behaviour. Traditionally evidence for learning is examined experimentally by studying spatial memory. However, tools developed for analysing tracking data from widely ranging animals allow a more holistic analysis of behaviour. Here we use the two together in novel combination of experimental and modelling approaches to analyse how patterns of hummingbird movements change as birds learn to find a reward in a location indicated by a pair of landmarks. Using hidden Markov models (HMMs) we identified two movement states which we interpret as Search and Travel and compared these to experimental behavioural measures of spatial memory. When birds had a single training trial to learn a flower’s location, both the behavioural measures and HMMs showed that hummingbirds relied on landmarks to guide search. Hummingbirds focussed hovering around the rewarded location and were more likely to be in the Search state, and more likely to switch from Travel to Search, when closer to the rewarded location, but only when the landmarks were present. When birds had had 12 additional training trials, however, the HMMs and behavioural measures showed differences in how reliant birds were on landmarks. While behaviours like hovering were still strongly affected by removing landmarks, the likelihood of being in or entered the Search state was the same regardless of whether the landmarks were present or removed. These results suggests that hummingbirds rapidly learn to use nearby landmarks to structure where they search, but as birds gain experience the role of these landmarks changes. While familiar local landmarks were still essential for precise search, experienced birds were able to use alternative cues to guide broad-scale transitions between behaviour. HMMs and traditional behavioural measures each capture a different aspect of this learning, with neither approach alone accurately described the role of landmarks in spatial learning.
Improved deterrence of birds using an artificial predator, the RobotFalcon
Authors: Storms Rolf F. , Carere Claudio , Musters Robert , van Gasteren Hans , Verhulst Simon , Hemelrijk Charlotte K. 
Published: May 2022

AbstractCollisions between birds and airplanes, bird strikes, can damage aircrafts, resulting in delays and cancellation of flights, costing the international civil aviation industry more than 1.4 billion U.S. dollars annually. Bird deterrence is therefore crucial, but the effectiveness of all available deterrence methods is limited. For example, live avian predators can be a highly effective deterrent, because potential prey will not habituate to them, but live predators cannot be controlled with sufficient precision. Thus, there is an urgent need for new deterrence methods. To this end we developed the RobotFalcon, a device that we modelled after the peregrine falcon, a cosmopolitan predator that preys on a large range of bird species. Mimicking natural hunting behaviour, we tested the effectiveness of the RobotFalcon to deter flocks of corvids, gulls, starlings and lapwings. We compared its effectiveness with that of a drone, and of conventional methods routinely applied at a military airbase. We show that the RobotFalcon scared away bird flocks from fields immediately, and these fields subsequently remained free of bird flocks for hours. The RobotFalcon outperformed the drone and the best conventional method at the airbase (distress calls). Importantly, there was no evidence that bird flocks habituated to the RobotFalcon. We propose the RobotFalcon to be a practical and ethical solution to drive away bird flocks with all advantages of live predators but without their limitations.HighlightsWe present and test a new method of deterring of deterring birds, the RobotFalcon.The RobotFalcon chased away flocks fast and prevented early returns.The RobotFalcon outperformed both a drone and convential methods.No evidence of habituation to the RobotFalcon was found during the study period.
Developmental timing of programmed DNA elimination in Paramecium tetraurelia recapitulates germline transposon evolutionary dynamics
Authors: Zangarelli Coralie , Arnaiz Olivier , Bourge Mickaël , Gorrichon Kevin , Jaszczyszyn Yan , Mathy Nathalie , Escoriza Loïc , Bétermier Mireille , Régnier Vinciane 
Published: May 2022

AbstractWith its nuclear dualism, the ciliate Paramecium constitutes an original model to study how host genomes cope with transposable elements (TEs). P. tetraurelia harbors two germline micronuclei (MIC) and a polyploid somatic macronucleus (MAC) that develops from the MIC at each sexual cycle. Throughout evolution, the MIC genome has been continuously colonized by TEs and related sequences that are removed from the somatic genome during MAC development. Whereas TE elimination is generally imprecise, excision of ∼45,000 TE-derived Internal Eliminated Sequences (IESs) is precise, allowing for functional gene assembly. Programmed DNA elimination is concomitant with genome amplification. It is guided by non-coding RNAs and repressive chromatin marks. A subset of IESs is excised independently of this epigenetic control, raising the question of how IESs are targeted for elimination. To gain insight into the determinants of IES excision, we established the developmental timing of DNA elimination genome-wide by combining fluorescence-assisted nuclear sorting with next-generation sequencing. Essentially all IESs are excised within only one endoreplication round (32C to 64C), while TEs are eliminated at a later stage. We show that time, rather than replication, controls the progression of DNA elimination. We defined four IES classes according to excision timing. The earliest excised IESs tend to be independent of epigenetic factors, display strong sequence signals at their ends and originate from the most ancient integration events. We conclude that old IESs have been optimized during evolution for early and accurate excision, by acquiring stronger sequence determinants and escaping epigenetic control.
HiCUP-Plus: a fast open-source pipeline for accurately processing large scale Hi-C sequence data
Authors: Kelly S. Thomas , Yuhara Satoshi 
Published: May 2022

AbstractHi-C is an unbiased genome-wide assay to study 3D chromosome conformation and gene-regulation. The HiCUP pipeline is an open-source tool to process Hi-C from massively parallel sequencing while accounting for biases specific to the restriction enzyme digests used. It is an excellent solution tailored to analyse this technique, however the latest aligner supported by the current release is Bowtie2. To improve the computational performance and mapping accuracy when using the HiCUP pipeline, we have modified it to optionally call the HiSAT2 and Dragen aligners. This allows using the HiCUP pipeline with 3rd party aligners, including the commercially-licensed high performance Dragen aligner. The HiCUP+ pipeline is modified extensively to be compatible with Dragen outputs while ensuring that the same results as the original pipeline can be reproduced with the Bowtie or Bowtie2 aligners. Using the highly accurate HiSAT2 or Dragen aligners produces larger outputs with a higher proportion of uniquely mapped read pairs. It is therefore feasible to leverage the reduced compute-time of Dragen to reduce compute costs and turnaround-time without compromising quality of results. The HiCUP pipeline and Dragen both compute rich summary information.
Haplotype-phased and chromosome-level genome assembly ofPuccinia polysora, a giga-scale fungal pathogen causing southern corn rust
Authors: Liang Junmin , Li Yuanjie , Dodds Peter N. , Figueroa Melania , Sperschneider Jana , Han Shiling , Tsui Clement K.M. , Zhang Keyu , Li Leifu , Ma Zhanhong , Cai Lei 
Published: May 2022

AbstractRust fungi are characterized by large genomes with high repeat content and have two haploid nuclei in most life stages, which makes achieving high-quality genome assemblies challenging. Here, we described a pipeline using HiFi reads and Hi-C data to assemble a gigabase-sized fungal pathogen,Puccinia polysoraf.sp.zeae, to haplotype-phased and chromosome-scale. The final assembled genome is 1.71 Gbp, with ~850 Mbp and 18 chromosomes in each haplotype, being currently one of the two giga-scale fungi assembled to chromosome level. Transcript-based annotation identified 47,512 genes for dikaryotic genome with a similar number for each haplotype. A high level of interhaplotype variation was found with 10% haplotype-specific BUSCO genes, 5.8 SNPs/kbp and structural variation accounting for 3% of the genome size. TheP. polysoragenome displayed over 85% repeat contents, with genome-size expansion and copy number increasing of species-specific orthogroups. Interestingly, these features did not affect overall synteny with otherPucciniaspecies having smaller genomes. Fine-time-point transcriptomics revealed seven clusters of co-expressed secreted proteins that are conserved between two haplotypes. The fact that candidate effectors interspersed with all genes indicated the absence of a “two-speed genome” evolution inP. polysora. Genome resequencing of 79 additional isolates revealed a clonal population structure ofP. polysorain China with low geographic differentiation. Nevertheless, a minor population differentiated from the major population by having mutations on secreted proteins includingAvrRppC, indicating the ongoing virulence to evade recognition byRppC, a major resistance gene in Chinese corn cultivars. The high-quality assembly provides valuable genomic resources for future studies on disease management and the evolution ofP. polysora.
Gene Novelties in Amphioxus Illuminate the Early Evolution of Deuterostomes
Authors: Xiong Qing , Yang Kevin Yi , Zeng Xi , Wang Mingqiang , Ng Patrick Kwok-Shing , Zhou Jun-Wei , Ng Judy Kin-Wing , Law Cherie Tsz-Yiu , Du Qiao , Xu Kejin , Falkenberg Laura Jane , Mao Bingyu , Chen Jun-Yuan , Tsui Stephen Kwok-Wing 
Published: May 2022

AbstractAmphioxus, as the best living proxy to the chordate ancestor, is considered an irreplaceable model organism for evolutionary studies of chordates and deuterostomes. In this study, a high-quality genome of the Beihai amphioxus,Branchiostoma belcheribeihai, wasde novoassembled and annotated. Within four amphioxus genomes, a wide range of gene novelties were identified, revealing new genes that share unexpectedly high similarities with those from non-metazoan species. These gene innovation events have played roles in a range of amphioxus adaptations, including innate immunity responses, adaptation to anaerobic environments, and regulation of calcium balance. The gene novelties related to innate immunity, such as a group of lipoxygenases and a DEAD-box helicase, boosted amphioxus immune responses. The novel genes for alcohol dehydrogenase and ferredoxin could aid in the anaerobic tolerance of amphioxus. A proximally arrayed cluster of EF-hand calcium-binding protein genes were identified to resemble those of bacteria. The copy number of this gene cluster was linearly correlated to the sea salinity of the collection region, suggesting that it may enhance their survival at different calcium concentrations. Collectively, this comprehensive study on gene novelties of amphioxus reveals insights into the early genome evolution of chordates and deuterostomes and provides valuable resources for future research.
Structure-Guided Identification of Critical Residues in the Vacuolar Na+,K+/H+ Antiporter NHX1 from Arabidopsis thaliana
Authors: Rombola-Caldentey Belen , Mendoza Imelda , Quintero Francisco J. , Pardo José M. 
Published: May 2022

ABSTRACTCation/Proton Antiporters (CPA) acting in all biological membranes help regulate the volume and pH of cells and of intracellular organelles. A key issue with these proteins is their structure-function relationships since they present intrinsic regulatory features that rely on structural determinants, including pH-sensitivity and the stoichiometry of ion exchange. Crystal structures are only available for prokaryotic CPA, whereas the eukaryotic ones have been modeled using the former as templates. Here we show an updated and improved structural model of the tonoplast-localized K+,Na+/H+ antiporter NHX1 of Arabidopsis as a representative of the vacuolar NHX family that is key to the accumulation of K+ into plant vacuoles. Conserved residues judged as functionally important were mutated and the resulting protein variants were tested for activity in the yeast Saccharomyces cerevisiae. Results indicate that residue N184 in the ND-motif characteristic of CPA1 could be replaced by the DD-motif of CPA2 family members with minimal consequences on activity, yet this residue may help to regulate the optimal pH range of the exchanger. Attempts to alter the electroneutrality of AtNHX1 by different combinations of amino acid replacements at N184, R353 and R390 residues resulted in inactive or partly active proteins with differential ability to control the vacuolar pH of the yeast.
The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency
Authors: Athanasouli Paraskevi , Balli Martina , De Jaime-Soguero Anchel , Boel Annekatrien , Papanikolaou Sofia , van der Veer Bernard K. , Janiszewski Adrian , Francis Annick , El Laithy Youssef , Lo Nigro Antonio , Aulicino Francesco , Koh Kian Peng , Pasque Vincent , Cosma Maria Pia , Verfaille Catherine , Zwijsen An , Heindryckx Bjorn , Nikolaou Christoforos , Lluis Frederic 
Published: May 2022

AbstractEarly during preimplantation development and in heterogeneous mouse embryonic stem cells (mESC) culture, pluripotent cells are specified towards either the primed epiblast or the primitive endoderm (PE) lineage. Canonical Wnt signaling is crucial for safeguarding naive pluripotency and embryo implantation, yet the role and relevance of canonical Wnt inhibition during early mammalian development remains unknown. Here, we demonstrate that transcriptional repression exerted by Wnt/TCF7L1 promotes PE differentiation of mESCs and in preimplantation inner cell mass. Time-series RNA sequencing and promoter occupancy data reveal that TCF7L1 binds and represses genes encoding essential naive pluripotency factors and indispensable regulators of the formative pluripotency program, including Otx2 and Lef1. Consequently, TCF7L1 promotes pluripotency exit and suppresses epiblast lineage formation, thereby driving cells into PE specification. Conversely, deletion of Tcf7l1 abrogates PE differentiation without restraining epiblast priming. Taken together, our study underscores the importance of transcriptional Wnt inhibition in regulating lineage segregation in ESCs and preimplantation embryo development as well as identifies TCF7L1 as key regulator of this process.