bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gaining comprehensive biological insight into chloroplast RNA editing by performing a broad-spectrum RNA-seq analysis
Authors: Zhang Aidi , Fang Jing , Jiang Xiaohan , Wang Tengfei , Zhang Xiujun 
Published: June 2020

AbstractBackgroundRNA editing is a post-transcriptional modification that complement variation at the DNA level. Until now, different RNA editing systems were found in the major eukaryotic lineages. However, the evolution trajectory in plant chloroplast remains unclear. To gain a better understanding of RNA editing in plant chloroplast, in this study, based on publicly available RNA-seq data across three plant lineages (fern, gymnosperm, and angiosperm), we provided a detailed analysis of RNA editing events in plant chloroplasts and discussed the evolution of RNA editing in land plants.ResultsThere were a total of 5,389 editing sites located in leaf chloroplast identified across 21 plants after rigorous screening. We found that the cluster of RNA editing sites across 21 plants complied with the phylogenetic tree based on linked protein sequences approximately, and majority (∼ 95%) of the editing events resulted in non-synonymous codon changes, RNA editing occurred in second codon position was mainly the largest. Additionally, RNA editing caused an overall increase in hydrophobicity of the resulting proteins. The analyses also revealed that there is an uneven distribution of editing sites among species, genes, and codon positions, the average RNA editing extent varied among different plant species as well as genes. Finally, we found that the loss of editing sites along angiosperm evolution is mainly occurring by reduce of cytosines content, fern plants has the highest cytosine content, with the evolution of plants, cytosine were lost in RNA edited genes.ConclusionsMany of the identified sites in our study have not been previously reported and represent a valuable data set for future research community. Our findings provide valuable information for evolution of RNA editing in plants.
Comprehensive characterization of internal and cuticle surface microbiota of laboratory-reared F1Anopheles albimanusoriginating from different sites
Authors: Dada Nsa , Benedict Ana Cristina , López Francisco , Lol Juan C. , Sheth Mili , Dzuris Nicole , Padilla Norma , Lenhart Audrey 
Published: June 2020

AbstractBackgroundResearch on mosquito-microbe interactions may lead to new tools for mosquito and mosquito-borne disease control. To date, such research has largely utilized laboratory-reared mosquitoes that typically lack the microbial diversity of wild populations. A logical progression in this area involves working under controlled settings using field-collected mosquitoes or, in most cases, their progeny. Thus, an understanding of how laboratory colonization affects the assemblage of mosquito microbiota would aid in advancing mosquito microbiome studies and their applications beyond laboratory settings.MethodsUsing high throughput 16S rRNA amplicon sequencing, we characterized the internal and cuticle surface microbiota of F1progeny of wild-caught adultAnopheles albimanusfrom four locations in Guatemala. A total of 132 late instar larvae and 135 2-5day old, non-blood-fed virgin adult females that were reared under identical laboratory conditions, were pooled (3 individuals/pool) and analyzed.ResultsResults showed geographical heterogeneity in both F1larval internal (p=0.001; pseudo-F= 9.53) and cuticle surface (p=0.001; pseudo-F= 8.51) microbiota, and only F1adult cuticle surface (p=0.001; pseudo-F= 4.5) microbiota, with a more homogenous adult internal microbiota (p=0.12; pseudo-F= 1.6) across collection sites. Overall, ASVs assigned toLeucobacter, Thorsellia, Chryseobacteriumand uncharacterizedEnterobacteriaceae, dominated F1larval internal microbiota, whileAcidovorax, Paucibacter, and uncharacterizedComamonadaceae, dominated the larval cuticle surface. F1adults comprised a less diverse microbiota compared to larvae, with ASVs assigned to the genusAsaiadominating both internal and cuticle surface microbiota, and constituting at least 70% of taxa in each microbial niche.ConclusionsThese results suggest that location-specific heterogeneity in filed mosquito microbiota can be transferred to F1progeny under normal laboratory conditions, but this may not last beyond the F1larval stage without adjustments to maintain field-derived microbiota. Our findings provide the first comprehensive characterization of laboratory-colonized F1An. albimanusprogeny from field-derived mothers. This provides a background for studying how parentage and environmental conditions differentially or concomitantly affect mosquito microbiome composition, and how this can be exploited in advancing mosquito microbiome studies and their applications beyond laboratory settings.
Ferrochelatase regulates retinal neovascularization
Authors: Sheik Pran Babu Sardar Pasha , White Darcy , Corson Timothy W. 
Published: June 2020

AbstractFerrochelatase (FECH) is the terminal enzyme in heme biosynthesis. We previously showed that FECH is required for endothelial cell growth in vitro and choroidal neovascularization in vivo. But FECH has not been explored in retinal neovascularization, which underlies diseases like proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the inhibition of FECH using genetic and chemical approaches in the oxygen-induced retinopathy (OIR) mouse model. In OIR mice, FECH expression is upregulated and co-localized with neovascular tufts. Partial loss-of-functionFechm1Pasmutant mice showed reduced retinal neovascularization and endothelial cell proliferation in OIR. An intravitreal injection of the FECH inhibitorN-methyl protoporphyrin had similar effects. Griseofulvin is an anti-fungal drug that inhibits FECH as an off-target effect. Strikingly, intravitreal griseofulvin blocked pathological tuft formation and revascularized areas of vasoobliteration faster than vehicle, suggesting potential as a FECH-targeting therapy. Ocular toxicity studies revealed that intravitreal injection of griseofulvin in adult mice does not disrupt retinal vasculature, function, or morphology. In sum, mutation and chemical inhibition ofFechreduces retinal neovascularization and promotes physiological angiogenesis, suggesting a dual effect on vascular repair upon FECH inhibition, without ocular toxicity. These findings suggest that FECH inhibitors could be repurposed to treat retinal neovascularization.
Microengineered 3D pulmonary interstitial mimetics highlight a critical role for matrix degradation in idiopathic pulmonary fibrosis
Authors: Matera Daniel L. , DiLillo Katarina M. , Smith Makenzee R. , Davidson Christopher D. , Parikh Ritika , Said Mohammed , Wilke Carole A. , Lombaert Isabelle M. , Arnold Kelly B. , Moore Bethany B. , Baker Brendon M. 
Published: June 2020

AbstractFibrosis is often untreatable and is characterized by aberrant tissue scarring from activated myofibroblasts. Although the extracellular matrix becomes increasingly stiff and fibrous during disease progression, how these physical cues impact myofibroblast differentiation in 3D is poorly understood. Here we describe a multicomponent hydrogel that recapitulates the 3D fibrous structure hallmark to the interstitial tissue regions where idiopathic pulmonary fibrosis (IPF) initiates. In contrast to findings on 2D hydrogels, myofibroblast differentiation in 3D was inversely correlated with hydrogel stiffness, but positively correlated with matrix fiber density. Employing a multi-step bioinformatics analysis of IPF patient transcriptomes andin vitropharmacologic screening, we identify matrix-metalloprotease activity to be essential for 3D but not 2D myofibroblast differentiation. Given our observation that compliant degradable 3D matrices amply support fibrogenesis, these studies demonstrate a departure from the established relationship between stiffness and myofibroblast differentiation in 2D, and provide a new 3D model for studying fibrosis.
A population-genomic approach for estimating selection on polygenic traits in heterogeneous environments
Authors: Gompert Zachariah 
Published: June 2020

AbstractStrong selection can cause rapid evolutionary change, but temporal fluctuations in the form, direction and intensity of selection can limit net evolutionary change over longer time periods. Fluctuating selection could affect molecular diversity levels and the evolution of plasticity and ecological specialization. Nonetheless, this phenomenon remains understudied, in part because of analytical limitations and the general difficulty of detecting selection that does not occur in a consistent manner. Herein, I fill this analytical gap by presenting an approximate Bayesian computation (ABC) method to detect and quantify fluctuating selection on poly-genic traits from population-genomic time-series data. I propose a model for environment-dependent phenotypic selection. The evolutionary genetic consequences of selection are then modeled based on a genotype-phenotype map. Using simulations, I show that the proposed method generates accurate and precise estimates of selection when the generative model for the data is similar to the model assumed by the method. Performance of the method when applied to an evolve-and-resequence study of host adaptation in the cowpea seed beetle (Cal-losobruchus maculatus) was more idiosyncratic and depended on specific analytical choices. Despite some limitations, these results suggest the proposed method provides a powerful approach to connect causes of (variable) selection to traits and genome-wide patterns of evolution. Documentation and open source computer software (fsabc) implementing this method are available from GitHub (https://github.com/zgompert/fsabc.git).
The burden of rare protein-truncating genetic variants on human lifespan
Authors: Liu Jimmy Z. , Chen Chia-Yen , Tsai Ellen A. , Whelan Christopher D. , Sexton David , John Sally , Runz Heiko 
Published: June 2020

AbstractGenetic predisposition is believed to contribute substantially to the age at which we die. Genome-wide association studies (GWAS) have implicated more than 20 genetic loci to phenotypes related to human lifespan1. However, little is known about how lifespan is impacted by gene loss-of-function. Through whole-exome sequencing of 238,239 UK Biobank participants, we assessed the relevance of protein-truncating variant (PTV) gene burden on individual and parental survival. We identified exome-wide (P<2.5e-6) significant associations betweenBRCA2, BRCA1, TET2, PPM1D, LDLR, EML2andDEDD2PTV-burden with human lifespan. Gene and gene-set PTV-burden phenome-wide association studies (PheWAS) further highlighted the roles of these genes in cancer and cardiovascular disease as relevant for overall survival. The overlap between PTV-burden and prior GWAS results was modest, underscoring the value of sequencing in well-powered cohorts to complement GWAS for identifying loci associated with complex traits and disease.
Cortical beta oscillations reflect the contextual gating of visual action feedback
Authors: Limanowski Jakub , Litvak Vladimir , Friston Karl 
Published: June 2020

AbstractIn sensorimotor integration, the brain needs to decide how its predictions should accommodate novel evidence by ‘gating’ sensory data depending on the current context. Here, we examined the oscillatory correlates of this process using magnetoencephalography (MEG). We used virtual reality to decouple visual (virtual) and proprioceptive (real) hand postures during a task requiring matching either modality’s grasping movements to a target oscillation. Thus, we rendered visual information either task-relevant or a (to-be-ignored) distractor. Under visuo-proprioceptive incongruence, occipital beta power decreased relative to congruence when vision was task-relevant but increased when it had to be ignored. Dynamic causal modelling (DCM) revealed that this interaction was best explained by diametrical, task-dependent changes in visual gain. These results suggest a crucial role for beta oscillations in sensorimotor integration; particularly, in the contextual gating (i.e., gain or precision control) of visual vs proprioceptive action feedback, depending on concurrent behavioral demands.
NON-AVIAN DINOSAUR EGGSHELL CALCITE CONTAINS ANCIENT, ENDOGENOUS AMINO ACIDS
Authors: Saitta Evan T. , Vinther Jakob , Crisp Molly K. , Abbott Geoffrey D. , Kaye Thomas G. , Pittman Michael , Bull Ian , Fletcher Ian , Chen Xinqi , Collins Matthew J. , Sakalauskaite Jorune , Mackie Meaghan , Dal Bello Federica , Dickinson Marc R. , Stevenson Mark A. , Donohoe Paul , Heck Philipp R. , Demarchi Beatrice , Penkman Kirsty E. H. 
Published: June 2020

AbstractRates of peptide bond hydrolysis and other diagenetic reactions are not favourable for Mesozoic protein survival. Proteins hydrolyse into peptide fragments and free amino acids that, in open systems such as bone, can leach from the specimen and be further degraded. However, closed systems are more likely to retain degradation products derived from endogenous proteins. Amino acid racemisation data in experimental and subfossil material suggests that mollusc shell and avian eggshell calcite crystals can demonstrate closed system behaviour, retaining endogenous amino acids. Here, high-performance liquid chromatography reveals that the intra-crystalline fraction of Late Cretaceous (estimated ~80 Ma) titanosaur sauropod eggshell is enriched in some of the most stable amino acids (Glx, Gly, Ala, and possibly Val) and those that racemise are fully racemic, despite being some of the slowest racemising amino acids. These results are consistent with degradation trends deduced from modern, thermally matured, sub-fossil, and ~3.8 Ma avian eggshell, as well as ~30 Ma calcitic mollusc opercula. Selective preservation of certain fully racemic amino acids, which do not racemise in-chain, along with similar concentrations of free versus total hydrolysable amino acids, likely suggests complete hydrolysis of original peptides. Liquid chromatography-tandem mass spectrometry supports this hypothesis by failing to detect any non-contamination peptide sequences from the Mesozoic eggshell. Pyrolysis-gas chromatography-mass spectrometry reveals pyrolysates consistent with amino acids as well as aliphatic hydrocarbon homologues that are not present in modern eggshell, suggestive of kerogen formation deriving from eggshell lipids. Raman spectroscopy yields bands consistent with various organic molecules, possibly including N-bearing molecules or geopolymers. These closed-system amino acids are possibly the most thoroughly supported non-avian dinosaur endogenous protein-derived constituents, at least those that have not undergone oxidative condensation with other classes of biomolecules. Biocrystal matrices can help preserve mobile organic molecules by trapping them (perhaps with the assistance of resistant organic polymers), but trapped organics are nevertheless prone to diagenetic degradation even if such reactions might be slowed in exceptional circumstances. The evidence for complete hydrolysis and degradation of most amino acids in the eggshell raises concern about the validity of reported polypeptide sequences from open-system non-avian dinosaur bone and other Mesozoic fossils.
Microplastics have shape- and polymer-dependent effects on soil processes
Authors: Lehmann Anika , Leifheit Eva F. , Gerdawischke Maurice , Rillig Matthias C. 
Published: June 2020

AbstractMicroplastics are a diverse and ubiquitous contaminant, a global change driver with potential to alter ecosystem properties and processes. Microplastic-induced effects in soils are manifold as microplastics differ in a variety of properties among which the shape is of special interest. Microplastic shapes can resemble natural forms or be dissimilar from natural objects. Our knowledge is limited regarding the impact of various microplastic shapes on soil processes. Therefore, we conducted this two-part research comprising a meta-analysis on published literature and a lab experiment focusing on microplastic shapes- and polymer-induced effects on soil aggregation and organic matter decomposition. We here focus on fibers, films, foams and fragments as microplastic shapes.In the meta-analysis, we revealed a strong research focus on fibrous and particulate microplastic materials, with films and foams neglected.Our experiment showed that microplastic shapes are important modulators of responses in soil aggregation and organic matter decomposition. Fibers, irrespective of their chemistry, negatively affected the formation of aggregates. This supported the shape dissimilarity hypothesis. However, for other shapes like foams and fragments, the polymer identity is clearly an important factor co-modulating the soil responses.Further research is needed to generate a data-driven foundation to build on our developing mechanistic understanding of the importance and consequences of microplastic shapes added to our soils.
Identification of long regulatory elements in the genome ofPlasmodium falciparumand other eukaryotes
Authors: Menichelli Christophe , Guitard Vincent , Martins Rafael M. , Lèbre Sophie , Lopez-Rubio Jose-Juan , Lecellier Charles-Henri , Bréhélin Laurent 
Published: June 2020

AbstractLong regulatory elements (LREs), such as CpG islands, polydA:dT tracts or AU-rich elements, are thought to play key roles in gene regulation but, as opposed to conventional binding sites of transcription factors, few methods have been proposed to formally and automatically characterize them. We present here a computational approach named DExTER dedicated to the identification of LREs and apply it to the analysis of the genomes of different eukaryotes includingP. falciparum. Our analyses show that all tested genomes contain several LREs that are somewhat conserved along evolution, and that gene expression can be predicted with surprising accuracy on the basis of these long regions only. Regulation by LREs exhibits very different behaviours depending on species and conditions. On Apicomplexa organisms, the process appears highly dynamic, with different LREs involved at different phases of their life cycle. For multicellular organisms, the same LREs are involved in all tissues, but a dynamic behavior is observed along embryonic development stages. InP. falciparum, whose genome is known to be strongly depleted of transcription factors, LREs appear to be of especially high importance, and our analyses show that they are involved in both transcriptomic and post-transcriptomic regulation mechanisms. Moreover, we demonstrated the biological relevance of one the LREs discovered by DExTER inP. falciparumusing anin vivoreporter assay. The source code (python) of DExTER is available at addresshttps://gite.lirmm.fr/menichelli/DExTER.
HiDRA-seq: High-Throughput SARS-CoV-2 Detection by RNA Barcoding and Amplicon Sequencing
Authors: Yángüez Emilio , White Griffin , Kreutzer Susanne , Opitz Lennart , Poveda Lucy , Sykes Timothy , Moccia Maria Domenica , Aquino Catharine , Schlapbach Ralph 
Published: June 2020

AbstractThe recent outbreak of a new coronavirus that causes a Severe Acute Respiratory Syndrome in humans (SARS-CoV-2) has developed into a global pandemic with over 6 million reported cases and more than 375,000 deaths worldwide. Many countries have faced a shortage of diagnostic kits as well as a lack of infrastructure to perform necessary testing. Due to these limiting factors, only patients showing symptoms indicating infection were subjected to testing, whilst asymptomatic individuals, who are widely believed to be responsible for the fast dispersion of the virus, were largely omitted from the testing regimes. The inability to implement high throughput diagnostic and contact tracing strategies has forced many countries to institute lockdowns with severe economic and social consequences. The World Health Organization (WHO) has encouraged affected countries to increase testing capabilities to identify new cases, allow for a well-controlled lifting of lockdown measures, and prepare for future outbreaks. Here, we propose HiDRA-seq, a rapidly implementable, high throughput, and scalable solution that uses NGS lab infrastructure and reagents for population-scale SARS-CoV-2 testing. This method is based on the use of indexed oligo-dT primers to generate barcoded cDNA from a large number of patient samples. From this, highly multiplexed NGS libraries are prepared targeting SARS-CoV-2 specific regions and sequenced. The low amount of sequencing data required for diagnosis allows the combination of thousands of samples in a sequencing run, while reducing the cost to approximately 2 CHF/EUR/USD per RNA sample. Here, we describe in detail the first version of the protocol, which can be further improved in the future to increase its sensitivity and to identify other respiratory viruses or analyze individual genetic features associated with disease progression.
Mucin granules are degraded in the autophagosome-lysosome pathway as a means of resolving airway mucous cell metaplasia
Authors: Sweeter JM , Kudrna K , Hunt K , Thomes P , Dickey BF , Brody SL , Dickinson JD 
Published: June 2020

AbstractExacerbations of muco-obstructive airway diseases such as COPD and asthma are associated with epithelial changes termed mucous cell metaplasia (MCM). The molecular pathways triggering MCM have been identified; however, the factors that regulate resolution are less well understood. We hypothesized that the autophagosome-lysosome pathway is required for resolution of MCM by degrading cytoplasmic mucins. We found increased intracellular levels of Muc5ac and Muc5b in autophagy-deficient mice. This difference was not due to defective mucin secretion. Instead, we found that Lamp1-labeled lysosomes surrounded mucin granules of mucous cells indicating that granules were being degraded. Using a model of resolution of mucous cell metaplasia in mice, we found increased lysosomal proteolytic activity that peaked in the days after inflammation. Autophagy-deficient mice had persistent accumulation of mucin granules that failed to decline due to reduced mucin degradation. We applied these findingsin vitroto human airway epithelial cells (AECs). Activation of autophagy by mTOR inhibition led to degradation of mucin granules in AECs. Our findings indicate that during peak and resolution phases of MCM, mucin granules can be degraded by autophagy. The addition of mucin degradation to the existing paradigm of production and secretion may more fully explain how the secretory cells handle excess amounts of cytoplasmic mucin and offers a therapeutic target to speed resolution of MCM in airway disease exacerbations.Abstract Figure
The use of CRISPR-Cas Selective Amplicon Sequencing (CCSAS) to reveal the eukaryotic microbiome of metazoans
Authors: Zhong Kevin Xu , Cho Anna , Deeg Christophe M. , Chan Amy M. , Suttle Curtis A. 
Published: June 2020

AbstractCharacterization of the eukaryotic microbiome is required to understand the role of microbial communities in health and disease. Such investigation relies on sequencing 18S ribosomal RNA genes (rDNA), which serve as taxonomic markers; however, this is compromised by contaminating host rDNA sequences. To overcome this problem, we developed CRISPR-Cas Selective Amplicon Sequencing (CCSAS), a high-resolution and efficient approach for characterizing eukaryotic microbiomes. CCSAS uses taxon-specific single-guide RNA (sgRNA) to direct Cas9 to cut 18S rDNA sequences of the host. Validation shows that >96.5% of rDNA amplicons from ten model organisms were cleaved, while rDNA from protists and fungi were unaffected. In oyster spat, CCSAS resolved ∼8.5-fold more taxa, and several additional major phylogenetic groups when compared to the best available alternative approach. We designed taxon-specific sgRNA for ∼16,000 metazoan and plant taxa, making CCSAS widely available for characterizing eukaryotic microbiomes that have largely been neglected because of methodological challenges.