bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional reprogramming during effector/flg22-triggered immune is independent of defense phytohormone signaling networks
Authors: Zhang Nailou , Fan Zhijin 
Published: September 2020

AbstractPlants rely on the innate immune system to sense and respond to a wide range of lifestyle pathogens and to facilitate their survival in natural ecosystems. Pathogen-associated molecular patterns (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) are designated as a two-branched system of innate immunity. Although PTI/ETI share a series of downstream molecular events, systematic analysis of convergent and divergent signaling in PTI/ETI is currently lacking. The phytohormones salicylic acid (SA) and jasmonic acid (JA) are considered to constitute the hormonal backbone of plant immunity, are functionally antagonistic, and play essential roles in defending against biotrophic and necrotrophic pathogens, respectively. However, the distinct performance of two phytohormones in PTI/ETI remains unclear. Here, we systemically investigate and validate the reprogramming of molecular networks during PTI and ETI. Using publicly availableArabidopsisRNA sequence data from 560 samples, we construct a co-expression network under Mock conditions and then explore the differential expression/co-expression changes during PTI, ETI, andPtoDC3000 infection. During PTI and ETI, one-third of genes in theArabidopsisgenome exhibit the same directional differential expression in a manner independent of JA/ethylene/PAD4/SA signaling but show differential co-expression patterns. However, the defense phytohormone network is required for defense againstPtoDC3000 infection. We also exhibit the use of this network in prioritizing genes that functioned closely with the proteins directly targeted by elicitors. Overall, this study will deepen our understanding of plant transcriptome in plant immunity and provide new insights into the mode of action of elicitors.
LIQA: Long-read Isoform Quantification and Analysis
Authors: Hu Yu , Fang Li , Chen Xuelian , Zhong Jiang F. , Li Mingyao , Wang Kai 
Published: September 2020

AbstractLong-read RNA sequencing (RNA-seq) technologies have made it possible to sequence full-length transcripts, facilitating the exploration of isoform-specific gene expression (isoform relative abundance and isoform-level TPM) over conventional short-read RNA-seq. However, long-read RNA-seq suffers from high per-base error rate, presence of chimeric reads or alternative alignments, and other biases, which require different analysis methods than short-read RNA-seq. Here we present LIQA (Long-read IsoformQuantification andAnalysis), an Expectation-Maximization based statistical method to quantify isoform expression and detect differential alternative splicing (DAS) events using long-read RNA-seq data. Rather than summarizing isoform-specific read counts directly as done in short-read methods, LIQA incorporates base-pair quality score and isoform-specific read length information to assign different weights across reads, which reflects alignment confidence. Moreover, LIQA can detect DAS events between conditions using isoform usage estimates. We evaluated LIQA’s performance on simulated data and demonstrated that it outperforms other approaches in characterizing isoforms with low read coverage and in detecting DAS events between two groups. We also generated one direct mRNA sequencing dataset and one cDNA sequencing dataset using the Oxford Nanopore long-read platform, both with paired short-read RNA-seq data and qPCR data on selected genes, and we demonstrated that LIQA performs well in isoform discovery and quantification. Finally, we evaluated LIQA on a PacBio dataset on esophageal squamous epithelial cells, and demonstrated that LIQA recovered DAS events that failed to be detected in short-read data. In summary, LIQA leverages the power of long-read RNA-seq and achieves higher accuracy in estimating isoform abundance than existing approaches, especially for isoforms with low coverage and biased read distribution. LIQA is freely available athttps://github.com/WGLab/LIQA.
Epigenetic clock and methylation studies in vervet monkeys
Authors: Jasinska Anna J. , Haghani Amin , Zoller Joseph A. , Li Caesar Z. , Arneson Adriana , Ernst Jason , Kavanagh Kylie , Jorgensen Matthew J , Mattison Julie A. , Wojta Kevin , Choi Oi-Wa , DeYoung Joseph , Li Xinmin , Rao Andrew W. , Coppola Giovanni , Freimer Nelson B. , Woods Roger P. , Horvath Steve 
Published: September 2020

ABSTRACTDNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes hypermethylated with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED, and genes possessing the trimethylated H3K27 mark in their promoters.The epigenetic clocks are expected to be useful for age estimation of wild-born animals and anti-aging studies in vervets.
Novel regulatory and transcriptional networks associated with resistance to platinum-based chemotherapy in ovarian cancer
Authors: Topouza Danai G. , Choi Jihoon , Nesdoly Sean , Tarnouskaya Anastasiya , Nicol Christopher J.B. , Duan Qing Ling 
Published: September 2020

AbstractBackgroundHigh-grade serous ovarian cancer (HGSOC) is a highly lethal gynecologic cancer, in part due to resistance to platinum-based chemotherapy reported among 20% of patients. This study aims to elucidate the biological mechanisms underlying chemotherapy resistance, which remain poorly understood.MethodsSequencing data (mRNA and microRNA) from HGSOC patients were analyzed to identify differentially expressed genes and co-expressed transcript networks associated with chemotherapy response. Initial analyses used datasets from The Cancer Genome Atlas and then replicated in two independent cancer cohorts. Moreover, transcript expression datasets and genomics data (i.e. single nucleotide polymorphisms) were integrated to determine potential regulation of the associated mRNA networks by microRNAs and expression quantitative trait loci (eQTLs).ResultsIn total, 196 differentially expressed mRNAs were enriched for adaptive immunity and translation, and 21 differentially expressed microRNAs were associated with angiogenesis. Moreover, co-expression network analysis identified two mRNA networks associated with chemotherapy response, which were enriched for ubiquitination and lipid metabolism, as well as three associated microRNA networks enriched for lipoprotein transport and oncogenic pathways. In addition, integrative analyses revealed potential regulation of the mRNA networks by the associated microRNAs and eQTLs.ConclusionWe report novel transcriptional networks and pathways associated with resistance to platinum-based chemotherapy among HGSOC patients. These results aid our understanding of the effector networks and regulators of chemotherapy response, which will improve drug efficacy and identify novel therapeutic targets for ovarian cancer.
Modulating the activities of chloroplasts and mitochondria promotes ATP production and plant growth
Authors: Voon Chia Pao , Law Yee-Song , Guan Xiaoqian , Lim Shey-Li , Xu Zhou , Chu Wing-Tung , Zhang Renshan , Sun Feng , Labs Mathias , Leister Dario , Pribil Mathias , Hronková Marie , Kubásek Jiří , Cui Yong , Jiang Liwen , Tsuyama Michito , Gardeström Per , Tikkanen Mikko , Lim Boon Leong 
Published: September 2020

AbstractEfficient photosynthesis requires a balance of ATP and NADPH production/consumption in chloroplasts and the exportation of reducing equivalents from chloroplasts is important for balancing stromal ATP/NADPH ratio. Here we showed that the overexpression of purple acid phosphatase 2 on the outer membranes of chloroplasts and mitochondria can streamline the production and consumption of reducing equivalents in these two organelles, respectively. A higher capacity of consumption of reducing equivalents in mitochondria can indirectly help chloroplasts to balance the ATP/NADPH ratio in stroma and recycle NADP+, the electron acceptors of the linear electron flow. A higher rate of ATP and NADPH production from the linear electron flow, a higher capacity of carbon fixation by the Calvin-Benson-Bassham cycle and a greater consumption of NADH in mitochondria, enhance photosynthesis in the chloroplasts, ATP production in the mitochondria, sucrose synthesis in the cytosol, and eventually boosting plant growth and seed yields in the overexpression lines.
Epigenomic patterns reflect irrigation and grafting in the grapevine clone ‘Chambourcin’
Authors: Williams Brigette R. , Edwards Christine E. , Kwasniewski Misha T. , Miller Allison J. 
Published: September 2020

AbstractAlthough DNA methylation has largely been shown to be stable in plants, mounting evidence indicates methylation patterns may reflect environmental sensitivity. Perennial plants experience seasonal and inter-annual environmental variation, and clonal replicates of some long-lived plants, including many perennial crops, survive in a broad range of environments. This makes perennial crops a compelling study system to investigate links between the plant epigenome and environmental variation. In this study, we used whole genome bisulfite sequencing and small RNA sequencing to characterize the epigenome in 12 clonal replicates of the winegrape cultivar ‘Chambourcin.’ We asked whether DNA methylation varied in response to a full factorial combination of irrigation and grafting treatments. We found signatures of both irrigation and grafting in the ‘Chambourcin’ epigenome, as well as compelling evidence for a unique interaction effect whereby grafting appeared to override or mitigate epigenomic changes associated with irrigation in ungrafted vines. These findings indicate that the epigenome responds to environmental and agronomic manipulations, suggesting the epigenome might be a mechanism underlying how long-lived, clonal plants respond at the molecular level to their environment. Further research is needed to assess the potential relevance of variation in DNA methylation to plant form and function, and to address the implications of environmentally-inducible patterns of DNA methylation on the adaptive capacity of long-lived woody perennials in nature and under cultivation.
Major oscillations in spontaneous home-cage activity with an infraradian periodicity in C57Bl/6 mice housed under constant conditions
Authors: Pernold K. , Rullman E. , Ulfhake B. 
Published: September 2020

AbstractUsing 14-20 months of cumulative 24/7 home-cage activity recorded with a non-intrusive technique and a data driven analytical approach, we here provide evidence for the existence of a circannual oscillation (1-2 SD of the mean, on average 65% higher during peak of highs than lows; P=7E-50) in spontaneous activity of male and female C57BL/6 mice held under constant barrier conditions (dark-light cycle 12/12 h (DL), temperature 21±1°C, humidity 40-60%). The periodicity of the season-like oscillation is in the range of 2-4 months (on average 97 days across cohorts of cages) and off-sets also responses to environmental stimuli but does not significantly alter the preference for activity during the dark hours of this nocturnal mouse strain (P=0.11 difference between highs and lows).The significance of this hitherto not recognized slow rhythmic alteration in spontaneous activity is further substantiated by its co-variation with the feeding behaviour of the mice. The absence of coordination within and between cohorts of cages or synchronization to the seasons of the year, suggests that the oscillation of in-cage activity and behavioural responses is generated by a free-running intrinsic oscillator devoid of synchronization with an out-of-cage environmental time-keeper. Since the variation over time has such a magnitude and correlate with the feeding behaviour it is likely that it will impact a range of long term experiments conducted on laboratory mice if left unrecognized.
Topological Assembly of a Deployable Hoberman Flight Ring from DNA
Authors: Li Ruixin , Chen Haorong , Choi Jong Hyun 
Published: September 2020

ABSTRACTDeployable geometries are finite auxetic structures that preserve their overall shapes during expansion and contraction. The topological behaviors emerge from intricately arranged elements and their connections. Despite considerable utility of such configurations in nature and in engineering, deployable nanostructures have never been demonstrated. Here we show a deployable flight ring, a simplified planar structure of Hoberman sphere, using DNA origami. The DNA flight ring consists of topologically assembled six triangles in two layers that can slide against each other, thereby switching between two distinct (open and closed) states. The origami topology is a trefoil knot, and its auxetic reconfiguration results in negative Poisson’s ratios. This work shows the feasibility of deployable nanoarchitectures, providing a versatile platform for topological studies and opening new opportunities for bioengineering.
Glioblastoma Cell Migration is Directed by Electrical Signals
Authors: Clancy Hannah , Pruski Michal , Lang Bing , Ching Jared , McCaig Colin D. 
Published: September 2020

AbstractBackground:Electric field (EF) directed cell migration (electrotaxis) is known to occur in glioblastoma multiforme (GBM) and neural stem cells, with key signaling pathways frequently dysregulated in GBM. One such pathway is EGFR/PI3K/Akt, which is down-regulated by peroxisome proliferator activated receptor gamma (PPARγ) agonists. We investigated the effect of electric fields on GBM differentiated and stem cell migration and whether this was affected by treatment with the PPARγ agonist pioglitazone.MethodsPrimary GBM cell lines were cultured as differentiated and glioma stem cells (GSCs) and then exposed to EFs using electrotaxis chambers and imaged with time lapse microscopy. Cells were then treated with varying concentrations of pioglitazone and/or its inhibitor GW9662 and their responses to EFs examined.ResultsWe demonstrated that GBM differentiated and GSCs have opposing preferences for anodal and cathodal migration, respectively. Pioglitazone treatment resulted in significantly decreased directed cell migration in both cell types. Western blot analysis did not demonstrate any change in PPARγ expression with and without exposure to EF.ConclusionsOpposing EF responses in primary GBM differentiated cells and GSCs can be inhibited chemically by pioglitazone, implicating GBM EF modulation as a potential target in preventing tumour recurrence.
Modeling the hemodynamic response function using simultaneous EEG-fMRI data and convolutional sparse coding analysis with rank-1 constraints
Authors: Prokopiou Prokopis C. , Kassinopoulos Michalis , Xifra-Porxas Alba , Boudrias Marie-Hélène , Mitsis Georgios D. 
Published: September 2020

AbstractOver the last few years, an increasing body of evidence points to the hemodynamic response function as an important confound of resting-state functional connectivity. Several studies in the literature proposed using blind deconvolution of resting-state fMRI data to retrieve the HRF, which can be subsequently used for hemodynamic deblurring. A basic hypothesis in these studies is that relevant information of the resting-state brain dynamics is condensed in discrete events resulting in large amplitude peaks in the BOLD signal. In this work, we showed that important information of resting-state activity, in addition to the larger amplitude peaks, is also concentrated in lower amplitude peaks. Moreover, due to the strong effect of physiological noise and head motion on the BOLD signal, which in many cases may not be completely removed after preprocessing, the neurophysiological origin of the large amplitude BOLD signal peaks is questionable. Hence, focusing on the large amplitude BOLD signal peaks may yield biased HRF estimates. To define discrete events of neuronal origins, we proposed using simultaneous EEG-fMRI along with convolutional sparse coding analysis. Our results suggested that events detected in the EEG are able to describe the slow oscillations of the BOLD signal and to obtain consistent HRF shapes across subjects under both task-based and resting-state conditions.
Long time-scale study of von Willebrand factor multimers in extensional flow
Authors: Kania S. , Oztekin A. , Cheng X. , Zhang X. F. , Webb E. B. 
Published: September 2020

AbstractExtensional flow-induced transitions from a compact to an unfolded conformation are explored for the human glycoprotein von Willebrand factor (vWF). Multimer unfolding is a crucial step in the process of blood clotting and protein size maintenance. Previous studies have shown that flow-induced conformational transitions are initiated by a thermally nucleated polymeric protrusion. Below a certain strain rate, such a transition is a rare event that cannot be studied using standard stochastic dynamic simulation. In the present study, we have employed Weighted Ensemble Brownian dynamic (WEBD) simulations to study rare events of conformation transition in extensional flow. Results are presented for the transition rate of VWF multimer unfolding, with concomitant analysis of the likelihood of pathological unfolding as a function of strain rate. Relative to the typical half-life of vWF proteins in the human body, results here indicate that pathological unfolding would not manifest for strain rate less than 2000 s−1.Statement of SignificancevWF multimers, as they transit through the circulation, are exposed to extensional flow multiple times, and the total exposure time to such intermittent extensional flow can be on the order of minutes to an hour. However, due to the time-scale limitation of Brownian dynamics simulation, all the present studies of vWF multimers are limited to a few seconds in total duration. Here, we have applied an enhanced sampling technique, i.e., Weighted Ensemble, in combination with Brownian dynamics to analyze the behavior of multimers in extensional flow at physiologically relevant time-scales of hours and longer. The findings presented here provide new physical insights into vWF behavior, including how it relates to hematological pathology, while also illustrating the time-scale bridging capability of the WEBD method.
Polee: RNA-Seq analysis using approximate likelihood
Authors: Jones Daniel C. , Ruzzo Walter L. 
Published: September 2020

AbstractThe analysis of mRNA transcript abundance with RNA-Seq is a central tool in molecular biology research, but often analyses fail to account for the uncertainty in these estimates, which can be significant, especially when trying to disentangle isoforms or duplicated genes. Preserving un-certainty necessitates a full probabilistic model of the all the sequencing reads, which quickly becomes intractable, as experiments can consist of billions of reads. To overcome these limitations, we propose a new method of approximating the likelihood function of a sparse mixture model, using a technique we call the Pólya tree transformation. We demonstrate that substituting this approximation for the real thing achieves most of the benefits with a fraction of the computational costs, leading to more accurate detection of differential transcript expression.AvailabilityThe method is implemented in a Julia package available fromhttps://github.com/dcjones/poleeContactdcjones@cs.washington.edu
Interactions between specific breeding system and ploidy play a critical role in increasing niche adaptability in a global food crop
Authors: Fumia Nathan , Rubinoff Daniel , Zenil-Ferguson Rosana , Khoury Colin K. , Pironon Samuel , Gore Michael A. , Kantar Michael B. 
Published: September 2020

AbstractUnderstanding the factors driving ecological and evolutionary interactions of economically important plant species is important for sustainability. Niches of crop wild relatives, including wild potatoes (SolanumsectionPetota), have received attention, however, such information has not been analyzed in combination with phylogenetic histories, genomic composition and reproductive systems. We used a combination of ordinary least-squares (OLS) and phylogenetic generalized least-squares (PGLM) analyses to identify the discrete climate classes that wild potato species inhabit in the context of breeding system and ploidy. Self-incompatible diploid or self-compatible polyploid species significantly increase the number of discrete climate niches inhabited. This result was sustained when correcting for phylogenetic non-independence in the linear model. Our results support the idea that specific breeding system and ploidy combinations increase niche divergence through the decoupling of geographical range and niche diversity, and therefore, these species may be of particular interest for crop adaptation to a changing climate.
Integration of constraint-based modelling with faecal metabolomics reveals large deleterious effects ofFusobacteriaspecies on community butyrate production
Authors: Hertel Johannes , Heinken Almut , Martinelli Filippo , Thiele Ines 
Published: September 2020

SummaryIntegrating constraint-based community modelling with population statistics, we introduce new theoretical concepts for interrogating the metabolic functions of the microbiome, applying them to a public metagenomic dataset consisting of 365 colorectal cancer cases (CRC) and 251 healthy controls. We found that 1) glutarate production capability was significantly enriched in CRC microbiomes and mechanistically linked to lysine fermentation inFusobacteriaspecies, 2) acetate and butyrate production potentials were lowered in CRC, 3) Fusobacteria presence had large negative ecological effects on community butyrate production in CRC and healthy controls. Validating the model predictions against faecal metabolomics, ourin silicoframeworks correctly predictedin vivospecies metabolite correlations with high accuracy. In conclusion, highlighting the value of combining statistical association studies within silicomodelling, this study delivers insights on the metabolic role ofFusobacteriain the gut, while providing a proof of concept for the validity of constraint-based community modelling.