bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological tuning of microRNAs in FAP-derived Extracellular Vesicles by HDAC inhibitors promotes regeneration and reduces fibrosis in dystrophic muscles
Authors: Sandonà M. , Consalvi S. , Tucciarone L. , Bardi M. De , Scimeca M. , Angelini D. , Buffa V. , D’Amico A. , Bertini E. , Cazzaniga S. , Bettica P. , Bouché M. , Bongiovanni A. , Puri P.L. , Saccone V. 
Published: February 2020

AbstractFunctional interactions between cellular components of the muscle stem cell (MuSC) niche regulate the regenerative ability of skeletal muscles in physiological and pathological conditions; however, the identity of the mediators of these interactions remains largely unknown. We show here that fibro-adipogenic progenitor (FAP)-derived Extracellular Vesicles (EVs) mediate microRNA transfer to MuSCs, and that exposure of dystrophic FAPs to HDAC inhibitors (HDACi) increases the intra-EV levels of a subset of microRNAs (miRs), which cooperatively target biological processes of therapeutic interest, including regeneration, fibrosis and inflammation. In particular, we found that increased levels of miR206 in EVs released from FAPs of muscles from Duchenne dystrophic patients or mice (mdx) exposed to HDACi were associated with enhanced regeneration and inhibition of fibrosis of dystrophic muscles. Consistently, EVs from HDACi-treated dystrophic FAPs could stimulated MuSC activation and expansion ex vivo, and promoted regeneration, while inhibiting fibrosis and inflammation of dystrophic muscles, upon intramuscular transplantation, in vivo. These data reveal a potential for pharmacological modulation of FAP-derived EV’s content as novel strategy for focal therapeutic interventions in Duchenne Muscular Dystrophy (DMD) and possibly other muscular diseases.Brief SummaryExtracellular Vesicles from HDACi-treated dystrophic FAPs promote regeneration, while inhibiting fibrosis and inflammation of dystrophic muscles
Genome-Wide Identification of Epigenetic Regulators inQuercus suber
Authors: Silva HG , Sobral RS , Magalhães AP , Morais-Cecílio L , Costa MMR 
Published: February 2020

AbstractModifications of DNA and histones, including methylation and acetylation, are critical for the epigenetic regulation of gene expression during plant development, particularly during environmental adaptation processes. However, information on the enzymes catalyzing all these modifications in perennial trees, such asQuercus suber, is still not available. In this study, several epigenetic modifier proteins, including eight DNA methyltransferases (DNA Mtases), three DNA demethylases (DDMEs) and ninety-one histone modifiers including thirty-five histone methyltransferases (HMTs), twenty-six histone demethylases (HDMTs), eight histone acetyltransferases (HATs) and twenty-two histone acetylases (HDACs) were identified inQ. suber. Phylogenetic analyses of the DNA and histone modifier proteins were performed using several plant species homologs, enabling the classification of theQ. suberproteins. Additionalin silicoanalysis showed that someQ. suberDNA Mtases, DMEs and histone modifiers have the typical domains found in the plant model Arabidopsis, which might suggest a conserved functional role. A link between the expression levels of each gene in differentQ. subertissues (buds, flowers, acorns, embryos, cork and roots) with the functions already known for their closest homologs in other species was also established. Therefore, the data generated here are important for future studies exploring the role of epigenetic regulators in this economically important species.
TheStreptomycesvolatile 3-octanone alters auxin/cytokinin and growth inArabidopsis thalianavia the gene familyKISS ME DEADLY
Authors: Dotson Bradley R. , Verschut Vasiliki , Flärdh Klas , Becher Paul G. , Rasmusson Allan G. 
Published: February 2020

AbstractPlants enhance their growth in the presence of particular soil bacteria due to volatile compounds affecting the homeostasis of plant growth hormones. However, the mechanisms of volatile compound signaling and plant perception has been unclear. This study identifies the bioactive volatile 3-octanone as a plant growth stimulating volatile, constitutively emitted by the soil bacteriumStreptomyces coelicolorgrown on a rich medium. When 3-octanone is applied to developingArabidopsis thalianaseedlings, a family-wide induction of the Kelch-repeat F-box genes known asKISS ME DEADLY(KMD) subsequently alters auxin/cytokinin homeostasis to promote the growth of lateral roots and inhibit the primary root. Loss of function of theKMDfamily or other alterations of auxin/cytokinin homeostasis suppresses the volatile-induced growth response. This reveals a function ofKMDs in the pathway of microbial volatile perception and plant growth responses.Significance StatementVolatiles from soil microbes are profound stimulators of plant growth. This work identifies for the first time a plant hormone signaling regulator, the gene familyKISS ME DEADLY(KMD), to be an early essential step in plant growth promotion by a soil bacterial volatile, 3-octanone. TheKMD-regulated gene network alters the tissue sensitivity balance for the growth hormones auxin and cytokinin, modifying root growth rate and architecture. Previously, the Kelch repeat F-box gene family ofKMDs have been shown to be important down-regulators of both positive cytokinin signaling and phenylpropanoid biosynthesis, but upstream cues were unknown. This report places theKMDfamily regulation of plant growth and defense into its biotic context.
Emergence and diversification of a highly invasive chestnut pathogen lineage across south-eastern Europe
Authors: Stauber Lea , Badet Thomas , Prospero Simone , Croll Daniel 
Published: February 2020

AbstractInvasive microbial species constitute a major threat to biodiversity, agricultural production and human health. Invasions are often dominated by one or a small number of genotypes, yet the underlying factors driving invasions are poorly understood. The chestnut blight fungusCryphonectria parasiticafirst decimated the American chestnut and a recent outbreak threatens European chestnut trees. To unravel the mechanisms underpinning the invasion of south-eastern Europe, we sequenced 188 genomes of predominantly European strains. Genotypes outside of the invasion zone showed high levels of diversity with evidence for frequent and ongoing recombination. The invasive lineage emerged from the highly diverse European genotype pool rather than a secondary introduction from Asia. The expansion across south-eastern Europe was mostly clonal and is dominated by a single mating type suggesting a fitness advantage of asexual reproduction. Our findings show how an intermediary, highly diverse bridgehead population gave rise to an invasive, largely clonally expanding pathogen.Data availabilityAll raw sequencing data is available on the NCBI Short Read Archive (BioProject PRJNA604575)
Helicobactersmall RNA regulates host adaptation and carcinogenesis
Authors: Kinoshita-Daitoku Ryo , Kiga Kotaro , Otsubo Ryota , Ogura Yoshitoshi , Sanada Takahito , Bo Zhu , Phuoc Tuan Vo , Okano Tokuju , Iida Tamako , Yokomori Rui , Kuroda Eisuke , Hirukawa Sayaka , Tanaka Mototsugu , Sood Arpana , Subsomwong Phawinee , Ashida Hiroshi , Binh Tran Thanh , Nguyen Lam Tung , Van Khien Vu , Dung Ho Dang Quy , Nakai Kenta , Suzuki Toshihiko , Yamaoka Yoshio , Hayashi Tetsuya , Mimuro Hitomi 
Published: February 2020

AbstractType-1 carcinogenicHelicobacter pylorithat is known to evolve during long-term infection, enters the stomach orally and causes gastric cancer using the carcinogenic protein CagA1. However, little is known about the adaptation mechanisms ofH. pyloriwhen the environment changes from the outside to the inside of the living body. Here we show that small non-coding RNA HPnc4160 is a crucial novel RNA molecule ofH. pylorithat negatively regulates bacterial-host adaptation and gastric cancer.H. pyloriisolated from gerbil’s stomachs eight weeks post-infection acquired mutations in the increased number of T-repeats within the upstream region of the HPnc4160 coding region, which leads to reduced HPnc4160 expression levels that also seen in cancer patients-derivedH. pylori. By comparing RNA-seq and iTRAQ analysis between wild-type andhpnc4160deficient mutant strains, we identified eight targets of HPnc4160 includingcagAand unknown factors. Mice infection experiment revealed that thehpnc4160deficient mutant had a higher number of colonized bacteria in the mice stomach than the wild-type strain, indicating that reduced expression levels of HPnc4160 was important for bacterial host adaptation. The expression level of HPnc4160 was lower in the clinical isolates derived from gastric cancer patients compared with non-cancer-derived strains, while the mRNA expression levels of target factors were higher. Our findings highlight the first discovery that HPnc4160 is an important small RNA for bacteria to adapt to the host environment leading to gastric carcinogenesis.
High-qualityde novogenome assembly ofKappaphycus alvareziibased on both PacBio and HiSeq sequencing
Authors: Jia Shangang , Wang Guoliang , Liu Guiming , Qu Jiangyong , Zhao Beilun , Jin Xinhao , Zhang Lei , Yin Jinlong , Liu Cui , Shan Guangle , Wu Shuangxiu , Song Lipu , Liu Tao , Wang Xumin , Yu Jun 
Published: February 2020

ABSTRACTThe red algaeKappaphycus alvareziiis the most important aquaculture species inKappaphycus, widely distributed in tropical waters, and it has become the main crop of carrageenan production at present. The mechanisms of adaptation for high temperature, high salinity environments and carbohydrate metabolism may provide an important inspiration for marine algae study. Scientific background knowledge such as genomic data will be also essential to improve disease resistance and production traits ofK. alvarezii. 43.28 Gb short paired-end reads and 18.52 Gb single-molecule long reads ofK. alvareziiwere generated by Illumina HiSeq platform and Pacbio RSII platform respectively. Thede novogenome assembly was performed using Falcon_unzip and Canu software, and then improved with Pilon. The final assembled genome (336 Mb) consists of 888 scaffolds with a contig N50 of 849 Kb. Further annotation analyses predicted 21,422 protein-coding genes, with 61.28% functionally annotated. Here we report the draft genome and annotations ofK. alvarezii, which are valuable resources for future genomic and genetic studies inKappaphycusand other algae.
The significance of mitochondrial DNA half-life to the lifespan of post-mitotic cells
Authors: Holt Alan G , Davies Adrian M 
Published: February 2020

AbstractThe proliferation of mitochondrial DNA (mtDNA) with deletion mutations has been linked to aging, and age related neurodegenerative conditions. In this study we model effect of mtDNA half-life on mtDNA competition and selection.Individual cells effectively form a closed ecosystem containing a large population of independently replicating mtDNA. We would expect competition and selection to occur between wild type mtDNA and various mutant variants. There is a symbiotic relationship between the cell and the mitochondria, and unrestricted mtDNA replication would be detrimental to the host cell. Deletion mutations of mtDNA are relatively common and give a replication advantage to the shorter sequence, as this could be lethal to the host cell, we would expect to see differences in mtDNA replication in short and long lived cells.In this paper, we use a computer simulation of mtDNA replication, where mtDNA sequences may undergo deletion errors and give rise to mutant species that can compete with the wild type. This study focuses on longer lived cells where the wild type mtDNA is expected to be more susceptible to displacement by mutants. Our simulations confirm that deletion mutations have a replication advantage over the wild type due to decreased replication time. Wild type survival times diminished with increased mutation probabilities. The relationship between survival time and mutation rate was non-linear; a ten-fold increase in mutation probability resulted in a halving in wild type survival time.In contrast a modest increase in the mtDNA half-life had a profound affect on the wild type survival time in the presence of deletion mutants, thereby, mitigating the replicative advantage of shorter sequence mutations. Given the relevance of mitochondrial dysfunction to various neurodegenerative conditions, we propose that therapies to increase mtDNA half-life could be a therapeutic strategy.
Suppressing peatland methane production by electron snorkeling through pyrogenic carbon
Authors: Sun Tianran , Guzman Juan J. L. , Seward James D. , Enders Akio , Yavitt Joseph B. , Lehmann Johannes , Angenent Largus T. 
Published: February 2020

AbstractNorthern peatlands are experiencing more frequent fire events as a result of changing climate conditions. Forest fires naturally result in a direct and negative climate impact by emitting large amounts of carbon into the atmosphere. Recent studies show that this extensive emission may shift the soil carbon regime from a sink to a source. However, the fires also convert parts of the burnt biomass into pyrogenic carbon. Here, we show an indirect, but positive, climate impact induced by fire-derived pyrogenic carbon. We found that the accumulation of pyrogenic carbon reduced post-fire methane production from peatland soils by 13-24%. The conductive, capacitive, and redox-cycling electron transfer mechanisms enabled pyrogenic carbon to function as an electron snorkel, which redirected soil electron fluxes to facilitate alternative microbial respiration and reduced the rate of methane production by 50%. Given the fact that methane has a 34-fold greater warming potential than carbon dioxide, we estimate that global greenhouse gas emissions are reduced by 35 Tg CO2e annually through the electron snorkeling of pyrogenic carbon in peatlands. Our results highlight an important, but overlooked, function of pyrogenic carbon in neutralizing forest fire emissions and call for its consideration in the global carbon budget estimation.
Skeletonization of Plant Point Cloud Data in Stochastic Optimization Framework
Authors: Chaudhury Ayan , Godin Christophe 
Published: February 2020

AbstractSkeleton extraction from 3D plant point cloud data is an essential prior for myriads of phenotyping studies. Although skeleton extraction from 3D shapes have been studied extensively in the computer vision and graphics literature, handling the case of plants is still an open problem. Drawbacks of the existing approaches include the zigzag structure of the skeleton, nonuniform density of skeleton points, lack of points in the areas having complex geometry structure, and most importantly the lack of biological relevance. With the aim to improve existing skeleton structures of state-of-the-art, we propose a stochastic framework which is supported by the biological structure of the original plant (we consider plants without any leaves). Initially we estimate the branching structure of the plant by the notion of β-splines to form acurve treedefined as a finite set of curves joined in a tree topology with certain level of smoothness. In the next phase, we force the discrete points in the curve tree to move towards the original point cloud by treating each point in the curve tree as a center of Gaussian, and points in the input cloud data as observations from the Gaussians. The task is to find the correct locations of the Gaussian centroids by maximizing a likelihood. The optimization technique is iterative and is based on the Expectation Maximization (EM) algorithm. The E-step estimates which Gaussian the observed point cloud was sampled from, and the M-step maximizes the negative log-likelihood that the observed points were sampled from the Gaussian Mixture Model (GMM) with respect to the model parameters. We experiment with several real world and synthetic datasets and demonstrate the robustness of the approach over the state-of-the-art.
Infrared heater warming system markedly reduces dew formation: An overlooked factor in arid ecosystems
Authors: Feng Tianjiao , Zhang Lixu , Chen Qian , Ma Zhiyuan , Wang Hao , Shangguan Zijian , Wang Lixin , He Jin-Sheng 
Published: February 2020

ABSTRACTDew plays a vital role in ecosystem processes in arid and semi-arid regions and is expected to be affected by climate warming. Infrared heater warming systems have been widely used to simulate climate warming effects on ecosystem. However, how this warming system affects dew formation has been long ignored and rarely addressed. In a typical alpine grassland ecosystem on the Northeast of the Tibetan Plateau, we measured dew amount and duration by artificial condensing surfaces, leaf wetness sensors andin situdew formation on plants from 2012 to 2017. We also measured plant traits related to dew conditions. The results showed that (1) warming reduced the dew amount by 41.6%-91.1% depending on the measurement method, and reduced dew duration by 32.1 days compared to the ambient condition. (2) Different plant functional groups differed in dew formation. (3) Under the infrared warming treatment, the dew amount decreased with plant height, while under the ambient conditions, the dew amount showed the opposite trend. We concluded that warming with an infrared heater system greatly reduces dew formation, and if ignored, it may lead to overestimation of the effects of climate warming on ecosystem processes in climate change simulation studies.
Faster than thought: Detecting sub-second activation sequences with sequential fMRI pattern analysis
Authors: Wittkuhn Lennart , Schuck Nicolas W. 
Published: February 2020

AbstractNeural computations are often anatomically localized and executed on sub-second time scales. Understanding the brain therefore requires methods that offer sufficient spatial and temporal resolution. This poses a particular challenge for the study of the human brain because non-invasive methods have either high temporalorspatial resolution, but not both. Here, we introduce a novel multivariate analysis method for conventional blood-oxygen-level dependent functional magnetic resonance imaging (BOLD fMRI) that allows to study sequentially activated neural patterns separated by less than 100 ms with anatomical precision. Human participants underwent fMRI and were presented with sequences of visual stimuli separated by 32 to 2048 ms. Probabilistic pattern classifiers were trained on fMRI data to detect the presence of image-specific activation patterns in early visual and ventral temporal cortex. The classifiers were then applied to data recorded during sequences of the same images presented at increasing speeds. Our results show that probabilistic classifier time courses allowed to detect neural representations and their order, even when images were separated by only 32 ms. Moreover, the frequency spectrum of the statistical sequentiality metric distinguished between sequence speeds on sub-second versus supra-second time scales. These results survived when data with high levels of noise and rare sequence events at unknown times were analyzed. Our method promises to lay the groundwork for novel investigations of fast neural computations in the human brain, such as hippocampal replay.
Hierarchical coupling between ATP hydrolysis and Hsp90’s client binding site
Authors: Wolf Steffen , Sohmen Benedikt , Hellenkamp Björn , Thurn Johann , Stock Gerhard , Hugel Thorsten 
Published: February 2020

I.ABSTRACTSeveral indicators for a signal propagation from a binding site to a distant functional site have been found in the Hsp90 dimer. Here we determined a time-resolved pathway from ATP hydrolysis to changes in a distant folding substrate binding site. This was possible by combining single-molecule fluorescence-based methods with extensive atomistic nonequilibrium molecular dynamics simulations. We find that hydrolysis of one ATP effects a structural asymmetry in the full Hsp90 dimer that leads to the collapse of a central folding substrate binding site. Arg380 is the major mediator in transferring structural information from the nucleotide to the substrate binding site. This allosteric process occurs via hierarchical dynamics that involve timescales from picoto milliseconds and length scales from Ångstroms to several nanometers. We presume that similar hierarchical mechanisms are fundamental for information transfer through many other proteins.
Parkinson’s disease determinants, prediction and gene-environment interactions in the UK Biobank
Authors: Jacobs Benjamin M. , Belete Daniel , Bestwick Jonathan P , Blauwendraat Cornelis , Bandres-Ciga Sara , Heilbron Karl , Dobson Ruth , Nalls Mike A. , Singleton Andrew B. , Hardy John , Giovannoni Gavin , Lees Andrew J. , Schrag Anette , Noyce Alastair J ,   for The International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: February 2020

AbstractObjectiveTo systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson’s disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate existing risk prediction algorithms and the impact of including addition genetic risk on the performance of prediction.MethodsWe identified individuals with incident PD diagnoses (n=1276) and unmatched controls (n=500,406) in UK Biobank. We determined the association of risk factors with incident PD using adjusted logistic regression models. A polygenic risk score (PRS) was constructed and used to examine gene-environment interactions. The PRS was also incorporated into a previously-developed prediction algorithm for finding incident cases.ResultsStrong evidence of association (Pcorr<0.05) was found between PD and a positive family history of PD, a positive family history of dementia, non-smoking, low alcohol consumption, depression, and daytime somnolence, and novel associations with epilepsy and earlier menarche. Individuals with the highest 10% of PRS scores had increased risk of PD (OR=3.30, 95% CI 2.57-4.24) compared to the lowest risk decile. Higher PRS scores were associated with earlier age at PD diagnosis and inclusion of the PRS in the PREDICT-PD algorithm improved model performance (Nagelkerke pseudo-R20.0053, p=6.87×10−14). We found evidence of interaction between the PRS and diabetes.InterpretationHere we used UK Biobank data to reproduce several well-known associations with PD, to demonstrate the validity and predictive power of a polygenic risk score, and to demonstrate a novel gene-environment interaction, whereby the effect of diabetes on PD risk appears to depend on prior genetic risk for PD.