bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergent evolution of venom gland transcriptomes across Metazoa
Authors: Zancolli Giulia , Reijnders Maarten , Waterhouse Robert M. , Robinson-Rechavi Marc 
Published: July 2021

AbstractAnimals have repeatedly evolved specialized organs and anatomical structures to produce and deliver a cocktail of potent bioactive molecules to subdue prey or predators – venom. This makes it one of the most widespread convergent functions in the animal kingdom. Whether animals have adopted the same genetic toolkit to evolved venom systems is a fascinating question that still eludes us. Here, we performed the first comparative analysis of venom gland transcriptomes from 20 venomous species spanning the main Metazoan lineages, to test whether different animals have independently adopted similar molecular mechanisms to perform the same function. We found a strong convergence in gene expression profiles, with venom glands being more similar to each other than to any other tissue from the same species, and their differences closely mirroring the species phylogeny. Although venom glands secrete some of the fastest evolving molecules (toxins), their gene expression does not evolve faster than evolutionarily older tissues. We found 15 venom gland specific gene modules enriched in endoplasmic reticulum stress and unfolded protein response pathways, indicating that animals have independently adopted stress response mechanisms to cope with mass production of toxins. This, in turn, activates regulatory networks for epithelial development, cell turnover and maintenance which seem composed of both convergent and lineage-specific factors, possibly reflecting the different developmental origins of venom glands. This study represents the first step towards an understanding of the molecular mechanisms underlying the repeated evolution of one of the most successful adaptive traits in the animal kingdom.
Fly Cell Atlas: a single-cell transcriptomic atlas of the adult fruit fly
Authors: Li Hongjie , Janssens Jasper , De Waegeneer Maxime , Kolluru Sai Saroja , Davie Kristofer , Gardeux Vincent , Saelens Wouter , David Fabrice , Brbić Maria , Leskovec Jure , McLaughlin Colleen N. , Xie Qijing , Jones Robert C. , Brueckner Katja , Shim Jiwon , Tattikota Sudhir Gopal , Schnorrer Frank , Rust Katja , Nystul Todd G. , Carvalho-Santos Zita , Ribeiro Carlos , Pal Soumitra , Przytycka Teresa M. , Allen Aaron M. , Goodwin Stephen F. , Berry Cameron W. , Fuller Margaret T. , White-Cooper Helen , Matunis Erika L. , DiNardo Stephen , Galenza Anthony , O’Brien Lucy Erin , Dow Julian A. T. ,   FCA Consortium, Jasper Heinrich , Oliver Brian , Perrimon Norbert , Deplancke Bart , Quake Stephen R. , Luo Liqun , Aerts Stein 
Published: July 2021

AbstractThe ability to obtain single cell transcriptomes for stable cell types and dynamic cell states is ushering in a new era for biology. We created the TabulaDrosophilae, a single cell atlas of the adult fruit fly which includes 580k cells from 15 individually dissected sexed tissues as well as the entire head and body. Over 100 researchers from the fly community contributed annotations to >250 distinct cell types across all tissues. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types that are shared between tissues, such as blood and muscle cells, allowed the discovery of rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the entireDrosophilacommunity and serves as a comprehensive reference to study genetic perturbations and disease models at single cell resolution.
De novo human brain enhancers created by single nucleotide mutations
Authors: Li Shan , Hannenhalli Sridhar , Ovcharenko Ivan 
Published: July 2021

AbstractAdvanced human cognition is attributed to increased neocortex size and complexity, but the underlying gene regulatory mechanisms are unknown. Using deep learning model of embryonic neocortical enhancers, and human and macaque embryonic neocortex H3K27ac data, we identified ~4000 enhancers gained de novo in the human, largely attributable to single-nucleotide essential mutations. The genes near de novo gained enhancers exhibit increased expression in human embryonic neocortex relative to macaque, are involved in critical neural developmental processes, and are expressed specifically in the progenitor cells and interneurons. The gained enhancers, especially the essential mutations, are associated with central nervous system disorders/traits. Integrative computational analyses suggest that the essential mutations establish enhancer activities through affecting binding of key transcription factors of embryonic neocortex. Overall, our results suggest that non-coding mutations may have led to de novo enhancer gains in the embryonic human neocortex, that orchestrate the expression of genes involved in critical developmental processes associated with human cognition.
A New Likelihood-based Test for Natural Selection
Authors: Simon Helmut , Huttley Gavin 
Published: July 2021

ABSTRACTWe present a new statistic for testing for neutral evolution from allele frequency data summarised as a site frequency spectrum, which we call the relative likelihood neutrality test orρ. Classical methods of testing for natural selection, such as Tajima’s D and its relatives, require the null model to have constant population size over time and therefore can confound demographic change with natural selection.ρcan directly incorporate a null hypothesis reflecting general demographic histories. It has a natural Bayesian interpretation as an approximation to the log-probability of the null model, given the data. We use simulations to show thatρhas greater power than Tajima’s D to detect departure from neutrality for a range of scenarios of positive and negative selection. We also show howρcan be adapted to account for sequencing error. Application to the ACKR1 (FYO) gene in humans supported previous studies inferring positive selection in sub-Saharan populations which were based on inter-population comparisons. However, we did not find the signal of selection to be maximal in the region of the FY*O or Duffy-null allele in these populations. We also appliedρto investigate in greater detail a region on the 2q11.1 band of the human genome that has previously been identified as showing evidence of selection. This was done for a range of populations: for the European populations we incorporated a demographic history with a bottleneck corresponding to the putative out of Africa event. We were able to localise signals of selection to some specific regions and genes. Overall, we suggest thatρwill be a useful tool for identifying genomic regions that may be subject to natural selection.
High Sensitivity and Low-Cost Flavin luciferase (FLUX)-based Reporter Gene for Mammalian Cell Expression
Authors: Phonbuppha Jittima , Tinikul Ruchanok , Ohmiya Yoshihiro , Chaiyen Pimchai 
Published: July 2021

ABSTRACTLuciferase-based gene reporters generating bioluminescence signals are important tools for biomedical research. Amongst the luciferases, flavin-dependent enzymes use the most common, and thus most economical chemicals. However, their applications in mammalian cells are limited due to their low signals compared to other systems. Here, we constructed Flavin Luciferase for Mammalian Cell Expression (FLUX) by engineering luciferase from Vibrio campbellii (the most thermostable bacterial luciferase reported to date) and optimizing its expression and reporter assays in mammalian cells. We found that the FLUX reporter gene can be overexpressed in various cell lines and showed outstanding signal-to-background in HepG2 cells, significantly higher than that of firefly luciferase (Fluc). The combined use of FLUX/Fluc as target/control vectors gave the most stable signals, better than the standard set of Fluc(target)/Rluc(control). We demonstrated that FLUX can be used for testing inhibitors of the NF-κB signaling pathway, validating FLUX applications for various assays in the future.
ProXs drive the formation of membraneless organelles in plants
Authors: Zhang Honghong , Peng Fangyu , Liu Yan , Deng Haiteng , Fang Xiaofeng 
Published: July 2021

AbstractMembraneless organelles (MLOs) are non-membranous structures inside cells that organize cellular space and processes. The recent discovery that MLOs can be assembled via liquid-liquid phase separation (LLPS) advanced our understanding of these structures. However, the proteins that are capable of forming MLOs are largely unknown, especially in plants. In this study, we developed a method to identify proteins that we referred as ProXs (Proteins enriched by b-isoX) in Arabidopsis. Heterologous expression in yeast cells showed that most ProXs were capable of forming MLOs autonomously. We applied this method to several model and crop species including early and higher plants. This allowed us to generate an atlas of ProXs for studying plant MLOs. Analysis of ProXs from different species revealed high degree of conservation, supporting that they play important roles in cellular functions and are positively selected during evolution. Our method will be a valuable tool to characterize novel MLOs from desired cells and the data generated in present study will be instrumental for the plant research community to investigate MLO biology.
A SUBTILISIN-LIKE SERINE PROTEASE1 (OsSUBSrP1), plays an important role in the wax and cutin pathway, is essential for panicle development in rice
Authors: Ali Asif , Wu Tingkai , Zhang Hongyu , Xu Peizhou , Zafar Syed Adeel , Liao Yongxiang , Chen Xiaoqiong , Liu Yutong , Wang Wenming , Wu Xianjun 
Published: July 2021

AbstractPanicle degeneration is a severe physiological defect and causes reduction in grain yield. In this study, we characterized and presented the functional analysis of our previously reported mutant apa1331 (apical panicle abortion1331) that showed apical spikelet degeneration. The anthers from the apical spikelets of apa1331 were degenerated, pollen-less and showed lack of cuticle formation. Transverse sections showed normal meiosis till stage 5-6, however, defects in post-meiotic microspore development were found at stage 8-9 in apa1331. Measurement of wax and cutin analysis showed a significant reduction in anthers of apa1331 compared to Wildtype (WT). Quantification of H2O2 and MDA has indicated the excessive ROS (reactive oxygen species) in apa1331. Trypan blue staining, and TUNEL assay revealed cell death and excessive DNA fragmentation in apa1331. Map-based cloning and Mutmap analysis identified a candidate gene (LOC_Os04g40720) that is a SUBTILISIN-LIKE SERINE PROTEASE (OsSUBSrP1) which harbored an SNP (A>G) in apa1331. CRISPR-mediated knock-out lines of OsSUBSrP1 displayed spikelet degeneration comparable to apa1331. Global gene expression analysis revealed a significant downregulation of wax and cutin biosynthesis genes e.g., OsWDA1, OsMS2 and OsCER4 in apa1331. Our study reports the novel role of SUBSrP1 in ROS-mediated cell death in panicle development.Highlights1.OsSUBSrP1 plays an important role in maintaining ROS-mediated programmed cell death.2.OsSUBSrP1 is essential for apical spikelet development.3.OsSUBSrP1 regulates the expression of wax and cutin biosynthesis pathway genes.
Global evolutionary dynamics and resistome analysis of Clostridioides difficile ribotype 017
Authors: Imwattana Korakrit , Putsathit Papanin , Collins Deirdre A , Leepattarakit Teera , Kiratisin Pattarachai , Riley Thomas V , Knight Daniel R 
Published: July 2021

AbstractClostridioides difficile PCR ribotype (RT) 017 ranks among the most successful strains of C. difficile in the world. In the past three decades, it has caused outbreaks on four continents, more than other “epidemic” strains, however, our understanding of the genomic epidemiology underpinning the spread of C. difficile RT 017 is limited. Here, we performed high-resolution phylogenomic and Bayesian evolutionary analyses on an updated and more representative dataset of 282 non-clonal C. difficile RT 017 isolates collected worldwide between 1981 and 2019. These analyses place an estimated time of global dissemination between 1953 and 1983 and identified the acquisition of the ermB-positive transposon Tn6194 as a key factor behind global emergence. This coincided with the introduction of clindamycin, a key inciter of C. difficile infection, into clinical practice in the 1960s. Based on the genomic data alone, the origin of C. difficile RT 017 could not be determined, however, geographical data and records of population movement suggest that C. difficile RT 017 had been moving between Asia and Europe since the Middle Ages and was later transported to North America around 1860 (95% CI: 1622 – 1954). A focused epidemiological study of 45 clinical C. difficile RT 017 genomes from a cluster in a tertiary hospital in Thailand revealed that the population consisted of two groups of multidrug-resistant (MDR) C. difficile RT 017 and a group of early, non-MDR C. difficile RT 017. The significant genomic diversity within each MDR group suggests that although they were all isolated from hospitalised patients, there was likely a reservoir of C. difficile RT 017 in the community that contributed to the spread of this pathogen.Impact statementThis study utilises genomic sequence data from 282 non-clonal C. difficile ribotype (RT) 017 isolates collected from around the world to delineate the origin and spread of this epidemic lineage, as well as explore possible factors that have driven its success. It also reports a focused epidemiological investigation of a cluster of C. difficile RT 017 in a tertiary hospital in Thailand to identify possible sources of transmission in this specific setting.Data summaryAll new WGS data generated in this study has been submitted to the European Nucleotide Archive under the BioProject PRJEB44406 (sample accession ERS6268756 – ERS6268798). The complete genome of C. difficile MAR286 was submitted to GenBank under BioProject PRJNA679085 (accession CP072118). Details of all genomes included in the final analyses are available in the Supplementary Document, available at 10.6084/m9.figshare.14544792.
Model-informed target product profiles of long acting-injectables for use as seasonal malaria prevention
Authors: Burgert Lydia , Reiker Theresa , Golumbeanu Monica , Möhrle Jörg J. , Penny Melissa A. 
Published: July 2021

1.AbstractSeasonal malaria chemoprevention (SMC) has proven highly efficacious in reducing malaria incidence. However, the continued success of SMC is threatened by the spread of resistance against one of its main preventive ingredients, Sulfadoxine-Pyrimethamine(SP), operational challenges in delivery, and incomplete adherence to the regimens. Via a simulation study with an individual-based model of malaria dynamics, we provide quantitative evidence to assess long-acting injectables (LAIs) as potential alternatives to SMC. We explored the predicted impact of a range of novel preventive LAIs as a seasonal prevention tool in children aged three months to five years old during late-stage clinical trials and at implementation. LAIs were co-administered with a blood-stage clearing drug once at the beginning of the transmission season. We found the establishment of non-inferiority of LAIs to standard 3 or 4 rounds of SMC with SP-amodiaquine was challenging in clinical trial stages due to high intervention deployment coverage. However, our analysis of implementation settings where the achievable SMC coverage was much lower, LAIs with fewer visits per season are potential suitable replacements to SMC. Suitability as a replacement with higher impact is possible if the duration of protection of LAIs covered the duration of the transmission season. Furthermore, optimizing LAIs coverage and protective efficacy half-life via simulation analysis in settings with an SMC coverage of 60% revealed important trade-offs between protective efficacy decay and deployment coverage. Our analysis additionally highlights that for seasonal deployment for LAIs, it will be necessary to investigate the protective efficacy decay as early as possible during clinical development to ensure a well-informed candidate selection process.
Early life trauma leads to escalated aggressive behavior and its inheritance by impairing thyroid hormone availability in brain
Authors: Rawat Rohit Singh , Bhambri Aksheev , Pal Muneesh , Roy Avishek , Jain Suman , Pillai Beena , Konar Arpita 
Published: July 2021

AbstractEscalated and inappropriate levels of aggressive behavior referred to as pathological in psychiatry can lead to violent outcomes with detrimental impact on health and society. Early life trauma triggers adulthood violence and criminality, though molecular mechanisms remain elusive. Here, we provide prefrontal cortex and hypothalamus specific transcriptome profiles of peripubertal stress (PPS) exposed Balb/c adult male mice exhibiting escalated aggression and adult female mice resilient to such aberrant behavioral responses. We identify transthyretin (TTR) as a key regulator of PPS induced escalated aggression and its intergenerational inheritance. TTR mediated long-term perturbation in hypothalamic thyroid hormone (TH) availability contributed to male aggressive behavior without affecting circulating hormone. Ttr gene ablation in hypothalamus impaired local TH signaling including levels of TH transporters (Mct8, Oatp1c1), deiodinase 2(DIO2) and TH responsive genes (Nrgn, Trh and Hr). Escalated aggressive behavior and impaired TTR-TH signaling was also inherited in F1 male progenies. Further, we deciphered Ttr promoter hyper methylation in hypothalamus of such abnormally aggressive males across generations. Interestingly prefrontal cortex showed opposite pattern of Ttr expression as well as long term epigenetic changes. Also, T4 increase by levothyroxine in PFC did not produce any behavioral changes. Our findings reveal that trauma during puberty trigger lasting escalated aggression by epigenetic programming of TTR and consequent impaired thyroid availability in brain. TTR-TH signaling in brain can serve as potential target in reversal of escalated aggression and related psychopathologies.
Polygenic routes lead to parallel altitudinal adaptation in Heliosperma pusillum (Caryophyllaceae)
Authors: Szukala Aglaia , Lovegrove-Walsh Jessica , Luqman Hirzi , Fior Simone , Wolfe Thomas , Frajman Božo , Schönswetter Peter , Paun Ovidiu 
Published: July 2021

AbstractUnderstanding how organisms adapt to the environment is a major goal of modern biology. Parallel evolution - the independent evolution of similar phenotypes in different populations - provides a powerful framework to investigate the evolutionary potential of populations, the constraints of evolution, its repeatability and therefore its predictability. Here, we quantified the degree of gene expression and functional parallelism across replicated ecotype formation in Heliosperma pusillum (Caryophyllaceae), and gained insights into the architecture of adaptive traits. Population structure analyses and demographic modelling support a previously formulated hypothesis of parallel polytopic divergence of montane and alpine ecotypes. We detect a large proportion of differentially expressed genes (DEGs) underlying divergence within each replicate ecotype pair, with a strikingly low amount of shared DEGs across pairs. Functional enrichment of DEGs reveals that the traits affected by significant expression divergence are largely consistent across ecotype pairs, in strong contrast to the non-shared genetic basis. The remarkable redundancy of differential gene expression indicates a polygenic architecture for the diverged adaptive traits. We conclude that polygenic traits appear key to opening multiple routes for adaptation, widening the adaptive potential of organisms.
circFL-seq reveals full-length circular RNAs with rolling circular reverse transcription and nanopore sequencing
Authors: Liu Zelin , Tao Changyu , Li Shiwei , Du Minghao , Bai Yongtai , Hu Xueyan , Li Yu , Chen Jian , Yang Ence 
Published: July 2021

AbstractCircular RNAs (circRNAs) act through multiple mechanisms with their sequence features to fine-tune gene expression networks. Due to overlapping sequences with linear cognates, identifying internal sequences of circRNAs remains a great challenge, which hinders comprehensive understanding of circRNA functions and mechanisms. Here, based on rolling circular reverse transcription (RCRT) and nanopore sequencing, we developed circFL-seq, a full-length circRNA sequencing method, to profile circRNA at the isoform level. With a customized computational pipeline circfull to directly identify full-length sequences from rolling circular reads, we reconstructed 77,606 high-quality circRNAs from seven human cell lines and two human tissues. Benefiting from rolling circles and long-read sequencing, circFL-seq showed more than tenfold enrichment of circRNA reads and advantages for both detection and quantification at the isoform level compared to short-read RNA sequencing. The concordance of RT-qPCR and circFL-seq results for the identification of differential alternative splicing suggested wide application prospects for functional studies of internal variants in circRNAs. Moreover, the detection of cancer-related fusion circRNAs at the omics scale may further expand the application of circFL-seq. Together, the accurate identification and quantification of full-length circRNAs make circFL-seq a potential tool for large-scale screening of functional circRNAs.
Novel microbial syntrophies identified by longitudinal metagenomics
Authors: Raguideau Sebastien , Trego Anna , Farrell Fred , Collins Gavin , Quince Christopher , Soyer Orkun S 
Published: July 2021

ABSTRACTIdentifying species interactions in a microbial community and how this relates to community function is a key challenge. Towards addressing this challenge, we present here an extensive genome-resolved, longitudinal dataset and associated metadata. We collected weekly samples of microbial communities and recorded operating conditions from industrial methane producing anaerobic digestion reactors for a year. This allowed us to recover 2240 dereplicated metagenome assembled genomes (dMAGs), together with their coverage dynamics and functional annotations from which functional traits were inferred. Of these dMAGs, 1910 were novel species, with 22 representing novel orders and classes. Methanogenic communities are expected to be strongly structured by syntrophic and other associations between the methanogens and syntrophs that produce their substrates. We identified 450 potential syntrophic dMAGs by searching for pairs of methanogenic and non-methanogenic dMAGs that had highly correlated time-series. Genomes of potential syntrophs were enriched for oxidoreductases and sugar transport genes and there was a strong taxonomic signal in their associations with methanogens. Of particular note, we found that Bathyarchaeiea associated specifically with methanogens from the Thermoplasmata, and Thermococci classes. Same syntrophic associations were only rarely observed across multiple reactors, suggesting that syntrophies might be facultative, with particular strains within a species forming syntrophic associations only sometimes and not necessarily always with the same methanogenic partner. The presented results show that longitudinal metagenomics is a highly valuable approach for identifying species and their interactions in microbial communities.One Sentence SummaryLongitudinal study of microbial communities identifies novel species and predicts their interactions and role in community function.