bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA DLEU2 regulates Sirtuins and mitochondrial respiratory chain complex IV: a novel pathway in obesity and DOHaD
Authors: Zhang Jian , Kay Matthew Krivacka , Choudhury Mahua 
Published: May 2021

ABSTRACTLong noncoding RNAs (lncRNAs) are commonly dysregulated in cancer but are mostly unknown for roles in metabolic regulation. Sirtuins, an epigenetic modulator class, regulate metabolic pathways. However, how sirtuins are regulated via lncRNA is unknown. In our findings, DLEU2, a lncRNA involved in primarily blood cancers, and sirtuins were both significantly decreased in the livers of high-fat high-fructose diet (HFD-HF) fed male mouse offspring (F1) whose mothers (F0) were either fed chow diet or HFD-HF during reproductive and pregnancy windows. Confirming this connection, upon silencing DLEU2, transcription levels of SIRT1 through 6 and translational levels of SIRT1, 3, 5, and 6 were significantly downregulated. Knockdown of DLEU2 also significantly decreased the protein level of cytochrome-c oxidase (complex IV, MTCO1) without altering other mitochondrial complexes, leading to increased reactive oxygen species production. Interestingly, in F1 livers, the protein level of MTCO1 was also significantly decreased under an HFD-HF diet or even under chow diet if the mother was exposed to HFD-HF. Our findings therefore reveal for the first time that a lncRNA can regulate sirtuins and a specific mitochondrial complex, furthermore suggesting a potential role of DLEU2 in metabolic disorders over one or more generations.HIGHLIGHTSMaternal diet can modulate hepatic lncRNA DLEU2 and its downstream regulators in offspringDLEU2 is required for specific sirtuin regulation and mitochondrial respiration chain complex IV expressionOffspring liver depleted of DLEU2 show decreased mitochondrial respiration chain complex IV and specific sirtuins at transcriptional and translational levels
Performance evaluation of RNA purification kits and blood collection tubes in the Extracellular RNA Quality Control (exRNAQC) study
Authors:   The exRNAQC Consortium, Anckaert Jasper , Avila Cobos Francisco , Decock Anneleen , Decruyenaere Philippe , Deleu Jill , De Preter Katleen , De Wever Olivier , De Wilde Jilke , Dhondt Bert , D’huyvetter Thibaut , Everaert Celine , Fierro Carolina , Helsmoortel Hetty Hilde , Hendrix An , Hulstaert Eva , Koster Jan , Kuersten Scott , Mercer Tim R , Mestdagh Pieter , Morlion Annelien , Nijs Nele , Nuytens Justine , Philippron Annouck , Piofczyk Thomas , Poma-Soto Franco , Schoofs Kathleen , Schroth Gary P. , Thas Olivier , Vanden Eynde Eveline , Vandesompele Jo , Van Maerken Tom , Van Paemel Ruben , Verniers Kimberly , Verwilt Jasper , Yigit Nurten 
Published: May 2021

AbstractThe use of blood-based extracellular RNA (cell-free RNA; exRNA) as clinical biomarker requires the implementation of a validated procedure for sample collection, processing, and profiling. So far, no study has systematically addressed the pre-analytical variables affecting transcriptome analysis of exRNAs. In the exRNAQC study, we evaluated ten blood collection tubes, three time intervals between blood draw and downstream processing, and eight RNA purification methods using the supplier-specified minimum and maximum biofluid input volumes. The impact of these pre-analytics on deep transcriptome profiling of both small and messenger RNA from healthy donors’ plasma or serum was assessed for each pre-analytical variable separately and for interactions between a selected set of pre-analytics, resulting in 456 extracellular transcriptomes. Making use of 189 synthetic spike-in RNAs, the processing and analysis workflow was controlled. When comparing blood collection tubes, so-called preservation tubes do not stabilize exRNA well, and result in variable RNA concentration and sensitivity (i.e., the number of detected RNAs) over time, as well as compromised reproducibility. We also document large differences in RNA purification kit performance in terms of sensitivity, reproducibility, and observed transcriptome complexity, and demonstrate interactions between specific blood collection tubes, purification kits and time intervals. Our results are summarized in 11 performance metrics that enable an informed selection of the most optimal sample processing workflow for a given experiment. In conclusion, we put forward robust quality control metrics for exRNA quantification methods with validated standard operating procedures (SOPs), representing paramount groundwork for future exRNA-based precision medicine applications.
Evaluating brain parcellations using the distance controlled boundary coefficient
Authors: Zhi Da , King Maedbh , Hernandez-Castillo Carlos R. , Diedrichsen Jörn 
Published: May 2021

AbstractOne important approach to human brain mapping is to define a set of distinct regions that can be linked to unique functions. Numerous brain parcellations have been proposed, using cytoarchitectonic, structural or functional Magnetic Resonance Imaging (fMRI) data. The intrinsic smoothness of brain data, however, poses a problem for current methods seeking to compare different parcellations. For example, criteria that simply compare within-parcel to between-parcel similarity provide even random parcellations with a high value. Furthermore, the evaluation is biased by the spatial scale of the parcellation. To address this problem, we propose the Distance Controlled Boundary Coefficient (DCBC), an unbiased criterion to evaluate discrete parcellations. We employ this new criterion to evaluate existing parcellations of the human neocortex in their power to predict functional boundaries for an fMRI data set with many different tasks, as well as for resting-state data. We find that common anatomical parcellations do not perform better than chance, suggesting that task-based functional boundaries do not align well with sulcal landmarks. Parcellations based on resting-state fMRI data perform well; in some cases, as well as a parcellation defined on the evaluation data itself. Finally, multi-modal parcellations that combine functional and anatomical criteria perform substantially worse than those based on functional data alone, indicating that functionally homogeneous regions often span major anatomical landmarks. Overall, the DCBC advances the field of functional brain mapping by providing an unbiased metric that compares the predictive ability of different brain parcellations to define brain regions that are functionally maximally distinct.
Museum of Spatial Transcriptomics
Authors: Moses Lambda , Pachter Lior 
Published: May 2021

AbstractThe function of many biological systems, such as embryos, liver lobules, intestinal villi, and tumors depends on the spatial organization of their cells. In the past decade high-throughput technologies have been developed to quantify gene expression in space, and computational methods have been developed that leverage spatial gene expression data to identify genes with spatial patterns and to delineate neighborhoods within tissues. To assess the ability and potential of spatial gene expression technologies to drive biological discovery, we present a curated database of literature on spatial transcriptomics dating back to 1987, along with a thorough analysis of trends in the field such as usage of experimental techniques, species, tissues studied and computational approaches used. Our analysis places current methods in historical context, and we derive insights about the field that can guide current research strategies. A companion supplement offers a more detailed look at the technologies and methods analyzed:https://pachterlab.github.io/LP_2021/.
Direct photoresponsive inhibition of a p53-like transcription activation domain in PIF3 by Arabidopsis phytochrome B
Authors: Yoo Chan Yul , Sang Qing , He Jiangman , Qiu Yongjian , Long Lingyun , Kim Ruth Jean-Ae , Chong Emily G. , Hahm Joseph , Morffy Nicholas , Zhou Pei , Strader Lucia C. , Nagatani Akira , Mo Beixin , Chen Xuemei , Chen Meng 
Published: May 2021

ABSTRACTPhytochrome B (PHYB) triggers diverse light responses in Arabidopsis by binding to a group of antagonistically acting PHYTOCHROME-INTERACTING transcription FACTORs (PIFs) to promote PIF degradation, consequently downregulating PIF target genes. However, whether PHYB directly controls the transactivation activity of PIFs remains ambiguous. Here we show that the prototypic PIF, PIF3, possesses a p53-like transcription activation domain (TAD) consisting of a sequence-specific, hydrophobic activator motif surrounded by acidic residues. A PIF3mTAD mutant in which the activator motif is replaced with alanines fails to activate PIF3 target genes in Arabidopsis in dark, light, and shade conditions, validating the in vivo functions of the PIF3 TAD. Intriguingly, binding of PHYB’s N-terminal photosensory module to the PHYB-binding site adjacent to the TAD inhibits its transactivation activity. These results unveil a photoresponsive transcriptional switching mechanism in which photoactivated PHYB directly masks the transactivation activity of PIF3. Our study also suggests the unexpected conservation of sequence-specific TADs between the animal and plant kingdoms.
Rapid analysis of strigolactone receptor activity in aNicotiana benthamiana dwarf14mutant
Authors: White Alexandra R.F. , Mendez Jose A. , Khosla Aashima , Nelson David C. 
Published: May 2021

ABSTRACTDWARF14 (D14) is an ɑ/β-hydrolase and receptor for the plant hormone strigolactone (SL) in angiosperms. Upon SL perception, D14 works with MORE AXILLARY GROWTH2 (MAX2) to trigger polyubiquitination and degradation of DWARF53(D53)-type proteins in the SUPPRESSOR OF MAX2 1-LIKE (SMXL) family. We used CRISPR-Cas9 to generate knockout alleles of the two homoeologousD14genes in theNicotiana benthamianagenome. TheNbd14a,bdouble mutant had several phenotypes that are consistent with the loss of SL perception in other plants, including increased axillary bud outgrowth, reduced height, shortened petioles, and smaller leaves. A ratiometric fluorescent reporter system was used to monitor degradation of SMXL7 fromArabidopsis thaliana(AtSMXL7) after transient expression inN. benthamianaand treatment with the strigolactone analog GR24. AtSMXL7 was degraded after treatment with GR245DS, which has the stereochemical configuration of SLs, as well as its enantiomer GR24ent-5DS. InNbd14a,bleaves, AtSMXL7 abundance was unaffected by GR24. Transient coexpression of AtD14 with the AtSMXL7 reporter inNbd14a,brestored the degradation response to GR24, but required an active catalytic triad. With this platform, we evaluated the ability of several AtD14 mutants that had not been characterized in plants to target AtSMXL7 for degradation.
Structure supports function: informing directed and dynamic functional connectivity with anatomical priors
Authors: Pascucci David , Rubega Maria , Rué-Queralt Joan , Tourbier Sebastien , Hagmann Patric , Plomp Gijs 
Published: May 2021

AbstractThe dynamic repertoire of functional brain networks is constrained by the underlying topology of structural connections: the lack of a direct structural link between two brain regions prevents direct functional interactions. Despite the intrinsic relationship between structural (SC) and functional connectivity (FC), integrative and multimodal approaches to combine the two remain limited, especially for electrophysiological data. In the present work, we propose a new linear adaptive filter for estimating dynamic and directed FC using structural connectivity information as priors. We tested the filter in rat epicranial recordings and human event-related EEG data, using SC priors from a meta-analysis of tracer studies and diffusion tensor imaging metrics, respectively. Our results show that SC priors increase the resilience of FC estimates to noise perturbation while promoting sparser networks under biologically plausible constraints. The proposed filter provides intrinsic protection against SC-related false negatives, as well as robustness against false positives, representing a valuable new method for multimodal imaging and dynamic FC analysis.
Ultraviolet-A light increases mitochondrial anti-viral signaling protein in confluent human tracheal cells even at a distance from the light source
Authors: Leite Gabriela , Rezaie Ali , Mathur Ruchi , Barlow Gillian , Melmed Gil Y. , Pimentel Mark 
Published: May 2021

AbstractMitochondrial antiviral signaling (MAVS) protein mediates innate antiviral responses, including responses to certain coronaviruses such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have previously shown that ultraviolet-A (UVA) therapy can prevent virus-induced cell death in human ciliated tracheal epithelial cells (HTEpC) infected with coronavirus-229E, and that UVA treatment results in an increase in intracellular levels of MAVS. In this study, we set out to determine the mechanisms by which UVA light can activate MAVS, and whether local UVA light application can activate MAVS at locations distant from the light source (such as via cell-to-cell communication). MAVS levels were compared in HTEpC exposed to 2 mW/cm2 narrow band (NB)-UVA for 20 minutes and in unexposed controls, at 30-40% and at 100% confluency. MAVS levels were also compared in unexposed HTEpC treated with supernatants or lysates from UVA-exposed cells or from unexposed controls. Also, MAVS was assessed in different sections of confluent monolayer plates where only one section was exposed to NB-UVA. The results show that UVA increases the expression of MAVS protein. Cells in a confluent monolayer exposed to UVA were able to confer an elevation in MAVS in cells adjacent to the exposed section, and even cells in the most distant sections not exposed to UVA. In this study, human ciliated tracheal epithelial cells exposed to UVA demonstrate increased MAVS protein, and also appear to transmit this influence to distant confluent cells not exposed to light.
easyXpress: An R package to analyze and visualize high-throughput C. elegans microscopy data generated using CellProfiler
Authors: Nyaanga Joy , Crombie Timothy A. , Widmayer Samuel J. , Andersen Erik C. 
Published: May 2021

AbstractHigh-throughput imaging techniques have become widespread in many fields of biology. These powerful platforms generate large quantities of data that can be difficult to process and visualize efficiently using existing tools. We developed easyXpress to process and review C. elegans high-throughput microscopy data in the R environment. The package provides a logical workflow for the reading, analysis, and visualization of data generated using CellProfiler’s WormToolbox. We equipped easyXpress with powerful functions to customize the filtering of noise in data, specifically by identifying and removing objects that deviate from expected animal measurements. This flexibility in data filtering allows users to optimize their analysis pipeline to match their needs. In addition, easyXpress includes tools for generating detailed visualizations, allowing the user to interactively compare summary statistics across wells and plates with ease. Researchers studying C. elegans benefit from this streamlined and extensible package as it is complementary to CellProfiler and leverages the R environment to rapidly process and analyze large high-throughput imaging datasets.
Machine learning algorithms can predict tail biting outbreaks in pigs using feeding behaviour records
Authors: Ollagnier Catherine , Kasper Claudia , Wallenbeck Anna , Keeling Linda , Bee Giuseppe , Bigdeli Siavash A. 
Published: May 2021

AbstractTail biting is a damaging behaviour that impacts the welfare and health of pigs. Early detection of precursor sig outbreaks, using feeding behaviour data recorded by an electronic feeder. Prediction capacities of seven machine learning algorithms (Generalized Linear Model with Stepwise Feature Selection, random forest, Support Vector Machines with Radial Basis Function Kernel, Bayesian Generalized Linear Model, Neural network, K-nearest neighbour, and Partial Least Squares Discriminant Analysis) were evaluated from daily feeding data collected from 65 pens originating from two herds of grower-finisher pigs (25-100kg), in which 27 tail biting events occurred. Data were divided into training and testing data in two different ways, either by randomly splitting data into 75% (training set) and 25% (testing set), or by randomly selecting pens to constitute the testing set. In the first data splitting, the model is regularly updated with previous data from the pen, whereas in the second data splitting, the model tries to predict for a pen that it has never seen before. The K-nearest neighbour algorithm was able to predict 78% of the upcoming events with an accuracy of 96%, when predicting events in pens for which it had previous data. The detection of events for unknown pens was less sensitive, and the neural network model was able to detect 14% of the upcoming events with an accuracy of 63%. Our results indicate that machine learning models can be considered for implementation into automatic feeder systems for real-time prediction of tail biting events.
Unravelling consensus genomic regions conferring leaf rust resistance in wheat via meta-QTL analysis
Authors: Aduragbemi Amo , Soriano Jose Miguel 
Published: May 2021

AbstractLeaf rust, caused by the fungusPuccinia triticinaErikss (Pt), is a destructive disease affecting wheat and a threat to food security. Developing resistant varieties represents a useful method of disease control, and thus, understanding the genetic basis for leaf rust resistance is required. To this end, a comprehensive bibliographic search for leaf rust resistance quantitative trait loci (QTLs) was performed, and 393 QTLs were collected from 50 QTL mapping studies. Afterwards, a consensus map with a total length of 4567 cM consisting of different types of markers (SSR, DArT, Chip-based SNP markers and SNP markers from GBS) was used for QTL projection, and meta-QTL analysis was performed on 320 QTLs. A total of 75 genetic map positions (gmQTLs) were discovered and refined to 15 high confidence mQTLs (hcmQTLs). The candidate genes discovered within the hcmQTL interval were then checked for differential expression using data from three transcriptome studies, resulting in 92 differentially expressed genes (DEGs). The expression of these genes in various leaf tissues during wheat development was explored. This study provides insight into leaf rust resistance in wheat and thereby provides an avenue for developing resistant varieties by incorporating the most important hcmQTLs.
Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability
Authors: Geijer Marit E , Zhou Di , Selvam Kathiresan , Steurer Barbara , Evers Bastiaan , Mukherjee Chirantani , Cugusi Simona , van Toorn Marvin , van der Woude Melanie , Gong Wenzhi , Janssens Roel , Raams Anja , Lebbink Joyce HG , Geverts Bart , Plummer Dalton A , Bezstarosti Karel , Theil Arjan F , Mitter Richard , Houtsmuller Adriaan B , Vermeulen Wim , Demmers Jeroen AA , Li Shisheng , Lans Hannes , Bernards René , Svejstrup Jesper Q , Chaudhuri Arnab Ray , Wyrick John J , Marteijn Jurgen A 
Published: May 2021

AbstractCorrect transcription is crucial for life. However, DNA damage severely impedes elongating RNA Polymerase II (Pol II), causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions (TBLs). However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR/cas9 screen, we identified elongation factor ELOF1 as an important new factor in the transcription stress response upon DNA damage. We show that ELOF1 has an evolutionary conserved role in Transcription-Coupled Nucleotide Excision Repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair TBLs and resume transcription. Additionally, ELOF1 modulates transcription to protect cells from transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage by two distinct mechanisms.
Maxicircle architecture and evolutionary insights intoTrypanosoma cruzicomplex
Authors: Berná Luisa , Greif Gonzalo , Pita Sebastián , Faral-Tello Paula , Díaz-Viraqué Florencia , De Souza Rita De Cássia Moreira , Vallejo Gustavo Adolfo , Alvarez-Valin Fernando , Robello Carlos 
Published: May 2021

AbstractWe sequenced maxicircles fromT. cruzistrains representative of the species evolutionary diversity by using long-read sequencing, which allowed us to uncollapse their repetitive regions, finding that their real lengths range from 35 to 50 kb.T. cruzimaxicircles have a common architecture composed of four regions: coding region (CR), AT-rich region, short (SR) and long repeats (LR). Distribution of genes, both in order and in strand orientation are conserved, being the main differences the presence of deletions affecting genes coding for NADH dehydrogenase subunits, reinforcing biochemical findings that indicate that complex I is not functional inT. cruzi. Moreover, the presence of complete minicircles into maxicircles of some strains lead us to think about the origin of minicircles. Finally, a careful phylogenetic analysis was conducted using coding regions of maxicircles from up to 29 strains, and 1023 single copy nuclear genes from all of the DTUs, clearly establishing that taxonomicallyT. cruziis a complex of species composed by group 1 that contains clades A, B and D, and group 2 containing clade C. No significant differences were found in hybrid strains that justify the existence of TcV and Tc VI as separate clades: our results indicate that a unique event of hybridization between TcII and TcIII occurred. Three variants of maxicircles exist inT. cruzi: a, b and c, in correspondence with clades A, B, and C from mitochondrial phylogenies. While A and C carry maxicircles a and c respectively, both clades B and D carry b maxicircle variant; hybrid strains also carry the b- variant. We then propose a new nomenclature that is self-descriptive and makes use of both the phylogenetic relationships and the maxicircle variants present inT. cruzi.
Development and genetics of red coloration in the zebrafish relativeDanio albolineatus
Authors: Huang Delai , Lewis Victor M. , Toomey Matthew B. , Corbo Joseph C. , Parichy David M. 
Published: May 2021

AbstractAnimal pigment patterns play important roles in behavior and, in many species, red coloration serves as an honest signal of individual quality in mate choice. AmongDaniofishes, some species develop erythrophores, pigment cells that contain red ketocarotenoids, whereas other species, like zebrafish (D. rerio) only have yellow xanthophores. Here, we use pearl danio (D. albolineatus) to assess the developmental origin of erythrophores and their mechanisms of differentiation. We show that erythrophores in the fin ofD. albolineatusshare a common progenitor with xanthophores and maintain plasticity in cell fate even after differentiation. We further identify the predominant ketocarotenoids that confer red coloration to erythrophores and use reverse genetics to pinpoint genes required for the differentiation and maintenance of these cells. Our analyses are a first step towards defining the mechanisms underlying the development of erythrophore-mediated red coloration inDanioand reveal striking parallels with the mechanism of red coloration in birds.