bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-read sequencing reveals widespread intragenic structural variants in a recent allopolyploid crop plant
Authors: Chawla Harmeet Singh , Lee HueyTyng , Gabur Iulian , Tamilselvan-Nattar-Amutha Suriya , Obermeier Christian , Schiessl Sarah V. , Song Jia-Ming , Liu Kede , Guo Liang , Parkin Isobel A. P. , Snowdon Rod J. 
Published: January 2020

SummaryGenome structural variation (SV) contributes strongly to trait variation in eukaryotic species and may have an even higher functional significance than single nucleotide polymorphism (SNP). In recent years there have been a number of studies associating large, chromosomal scale SV ranging from hundreds of kilobases all the way up to a few megabases to key agronomic traits in plant genomes. However, there have been little or no efforts towards cataloging small (30 to 10,000 bp) to mid-scale (10,000 bp to 30,000 bp) SV and their impact on evolution and adaptation related traits in plants. This might be attributed to complex and highly-duplicated nature of plant genomes, which makes them difficult to assess using high-throughput genome screening methods. Here we describe how long-read sequencing technologies can overcome this problem, revealing a surprisingly high level of widespread, small to mid-scale SV in a major allopolyploid crop species,Brassica napus. We found that up to 10% of all genes were affected by small to mid-scale SV events. Nearly half of these SV events ranged between 100 bp to 1000 bp, which makes them challenging to detect using short read Illumina sequencing. Examples demonstrating the contribution of such SV towards eco-geographical adaptation and disease resistance in oilseed rape suggest that revisiting complex plant genomes using medium-coverage, long-read sequencing might reveal unexpected levels of functional gene variation, with major implications for trait regulation and crop improvement.
PDZ and LIM domain protein 2 plays dual and context-dependent roles in breast cancer development
Authors: Maryas Josef , Pribyl Jan , Bouchalova Pavla , Skladal Petr , Bouchal Pavel 
Published: January 2020

ABSTRACTBackgroundPDZ and LIM domain protein 2 (PDLIM2) is a cytoskeletal and nuclear effector that regulates the activity of several transcription factors (e.g., NF-κB, STAT), and its deregulation has been associated with oncogenesis. Our recent study identified PDLIM2 as a protein associated with the lymph node metastasis of low grade luminal A breast cancer tissues. Here, we aim to understand this association at the molecular and cellular levels.MethodsTo investigate the link between PDLIM2 and epithelial-to-mesenchymal transition (EMT), stably transduced MCF7-PDLIM2 cells, and MCF7 or MCF10A cells with PDLIM2 protein levels modified using siRNA orPDLIM2gene carrying plasmid, were used. Additionally, MCF7 and MCF10A cells were exposed to hypoxic conditions and TGFβ1 treatment. EMT was monitored using immunoblotting of EMT markers and atomic force microscopy (AFM). The role of PDLIM2 in cell migration and/or invasion was investigated using Transwell assay and xCELLigence system.ResultsFirst, we observe a positive effect of PDLIM2 overexpression on EMT in MCF7 cells, a model of luminal A tumors, using EMT markers and AFM. On the other hand, PDLIM2 helps to maintain the epithelial phenotype in MCF10A cells, a model of normal breast epithelial cells. Second, we find that exposure of the MCF7 cells to hypoxic conditions increases levels of PDLIM2 and carbonic anhydrase-9 (CA-9), a marker of the response to hypoxia. However, none of these effects are observed in the MCF10A cells. Third, PDLIM2 overexpression promotes migration, invasion, and proliferation and decreases adhesion of the MCF7 cells, but an opposite effect is observed in the MCF10A cells.ConclusionsOur data indicate that PDLIM2 plays a dual role: (i) as an EMT-supporting and hypoxia-responding oncoprotein in luminal breast cancer cells, and (ii) as an epithelial phenotype-maintaining tumor suppressor in normal epithelial breast cells.
Irrelevant Predictions: Distractor Rhythmicity Modulates Neural Encoding in Auditory Cortex
Authors: Makov Shiri , Zion-Golumbic Elana 
Published: January 2020

AbstractDynamic Attending Theory suggests that predicting the timing of upcoming sounds can assist in focusing attention towards them. However, whether similar predictive processes are also applied to background noises and assist in guiding attentionawayfrom potential distractors, remains an open question. Here we address this question by manipulating the temporal predictability of distractor sounds in a dichotic listening selective attention task. We tested the influence of distractors’ temporal predictability on performance and on the neural encoding of sounds, by comparing the effects of Rhythmic vs. Non-rhythmic distractors. Using Magnetoencephalography (MEG) we found that, indeed, the neural responses to both attended and distractor sounds were affected by distractors’ rhythmicity. Baseline activity preceding the onset of Rhythmic distractor sounds was enhanced relative to Non-rhythmic distractor sounds, and sensory response were suppressed. Moreover, when distractors were Rhythmic, responses to attended sounds were more strongly lateralized to the contra-lateral hemisphere. Behavioral performance also improved in the Rhythmic condition. These combined behavioral and neural results suggest that not only are temporal predictions formed for task-irrelevant sounds, but that these predictions bear functional significance for promoting selective attention and reducing distractibility.
Correlated motions of conserved polar motifs lay out a plausible mechanism of G protein-coupled receptor activation
Authors: Mitra Argha , Sarkar Arijit , Szabó Márton R. , Borics Attila 
Published: January 2020

ABSTRACTRecent advancements in the field of experimental structural biology have provided high-resolution structures of active and inactive state G protein-coupled receptors (GPCRs), a highly important pharmaceutical target family, but the process of transition between these states is poorly understood. According to the current theory, GPCRs exist in structurally distinct, dynamically interconverting functional states of which populations are shifted upon binding of ligands and intracellular signaling proteins. However, explanation of the activation mechanism on an entirely structural basis gets complicated when multiple activation pathways and active receptor states are considered. Our unbiased, atomistic molecular dynamics simulations of the mu-opioid receptor in a physiological environment revealed that external stimulus is propagated to the intracellular surface of the receptor through subtle, concerted movements of highly conserved polar amino acid side chains along the 7thtransmembrane helix. To amend the widely accepted theory we suggest that the initiation event of GPCR activation is the shift of macroscopic polarization between the ortho- and allosteric binding pockets and the intracellular G protein-binding interface.Abstract FigureTable of Contents Graphic
Simultaneous stimulation of RuBP regeneration and electron transport increases productivity and water use efficiency under field conditions
Authors: López-Calcagno Patricia E. , Brown Kenny L. , Simkin Andrew J. , Fisk Stuart J. , Lawson Tracy , Raines Christine A. 
Published: January 2020

AbstractPrevious studies have demonstrated that independent stimulation of either electron transport or RuBP regeneration can increase the rate of photosynthetic carbon assimilation and plant biomass. In this paper, we present evidence that a multi-gene approach to simultaneously manipulate these two processes provides a further stimulation of photosynthesis. We report on the introduction of the cyanobacterial bifunctional enzyme fructose-1,6-bisphosphatase/sedoheptulose-1,7-bisphosphatase or overexpression of the plant enzyme sedoheptulose-1,7-bisphosphatase, together with expression of the red algal protein cytochromec6, and show that a further increase in biomass accumulation under both glasshouse and field conditions can be achieved. Furthermore, we provide evidence that the simultaneous stimulation of electron transport and RuBP regeneration can lead to enhanced intrinsic water use efficiency under field conditions.One sentence summarySimultaneous stimulation of RuBP regeneration and electron transport results in improvements in biomass yield in glasshouse and field grown tobacco.
Dynamic Order in Allosteric Interactions
Authors: Türeli Sina , Haliloğlu Türkan 
Published: January 2020

AbstractAllostery is an intrinsic dynamic phenomenon that underlies functional long-distance interactions in proteins, which we study here by stochastic calculus approach to elastic network models (ENMs). We show that once you drop the usually accepted high friction limit and include hydrodynamic interactions in ENMs, a simple measure that uses the pairwise difference in the time-delayed correlations of residue fluctuations provides insight about functional sites and their dynamical behaviour in allosteric communication. We present this with three exemplary cases Aspartate Carbamoyl transferase, Insulin Receptor and DNA-dependent Protein Kinase. We show that proteins possess characteristic pathways operating at different time-delay windows with slow to faster motions underlying the protein function. As these pathways help communication between key residues of functionality, they can also be used to identify their locations without any prior knowledge other than the protein crystal structure.
pH effect on strain-specific transcriptomes of the take-all fungus
Authors: Gazengel Kévin , Lebreton Lionel , Lapalu Nicolas , Amselem Joëlle , Guillerm-Erckelboudt Anne-Yvonne , Tagu Denis , Daval Stéphanie 
Published: January 2020

AbstractThe soilborne fungusGaeumannomyces graminisvar.tritici(Ggt) causes the take-all disease on wheat roots. Ambient pH has been shown to be critical in different steps ofGgtlife cycle such as survival in bulk soil, saprophytic growth, and pathogenicity on plants. There are however intra-specific variations and we previously found two types ofGgtstrains that grow preferentially either at acidic pH or at neutral/alkaline pH; gene expression involved in pH-signal transduction pathway and pathogenesis was differentially regulated in two strains representative of these types. To go deeper in the description of the genetic pathways and the understanding of this adaptative mechanism, transcriptome sequencing was achieved on two strains (PG6 and PG38) which displayed opposite growth profiles in two pH conditions (acidic and neutral). PG6, growing better at acidic pH, overexpressed in this condition genes related to energy production and protein deubiquitination. In contrast, PG38, which grew better at neutral pH, overexpressed in this condition genes involved in fatty acids metabolism. This strain also expressed stress resistance mechanisms at both pH, to assert a convenient growth under various ambient pH conditions. These differences in metabolic pathway expression between strains at different pH might buffer the effect of field or soil variation in wheat fields, and explain the success of the pathogen.
Water and phosphorus uptake by upland rice root systems unraveled under multiple scenarios: linking a 3D soil-root model and data
Authors: Mai Trung Hieu , Bauw Pieterjan De , Schnepf Andrea , Merckx Roel , Smolders Erik , Vanderborght Jan 
Published: January 2020

AbstractBackground and aimsUpland rice is often grown where water and phosphorus (P) are limited and these two factors interact on P bioavailability. To better understand this interaction, mechanistic models representing small-scale nutrient gradients and water dynamics in the rhizosphere of full-grown root systems are needed.MethodsRice was grown in large columns using a P-deficient soil at three different P supplies in the topsoil (deficient, suboptimal, non-limiting) in combination with two water regimes (field capacity versus drying periods). Root architectural parameters and P uptake were determined. Using a multiscale model of water and nutrient uptake, in-silico experiments were conducted by mimicking similar P and water treatments. First, 3D root systems were reconstructed by calibrating an architecure model with observed phenological root data, such as nodal root number, lateral types, interbranch distance, root diameters, and root biomass allocation along depth. Secondly, the multiscale model was informed with these 3D root architectures and the actual transpiration rates. Finally, water and P uptake were simulated.Key resultsThe plant P uptake increased over threefold by increasing P and water supply, and drying periods reduced P uptake at high but not at low P supply. Root architecture was significantly affected by the treatments. Without calibration, simulation results adequately predicted P uptake, including the different effects of drying periods on P uptake at different P levels. However, P uptake was underestimated under P deficiency, a process likely related to an underestimated affinity of P uptake transporters in the roots. Both types of laterals (i.e. S- and L-type) are shown to be highly important for both water and P uptake, and the relative contribution of each type depend on both soil P availability and water dynamics. Key drivers in P uptake are growing root tips and the distribution of laterals.ConclusionsThis model-data integration demonstrates how multiple co-occurring single root phene responses to environmental stressors contribute to the development of a more efficient root system. Further model improvements such as the use of Michaelis constants from buffered systems and the inclusion of mycorrhizal infections and exudates are proposed.
Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near humanKRT8/18
Authors: Liu Huan , Duncan Kaylia , Helverson Annika , Kumari Priyanka , Mumm Camille , Xiao Yao , Carlson Jenna , Darbellay Fabrice , Visel Axel , Leslie Elizabeth , Breheny Patrick , Erives Albert , Cornell Robert A. 
Published: January 2020

AbstractGenome wide association studies for non-syndromic orofacial cleft (OFC) have identified single nucleotide polymorphisms (SNPs) at loci where the presumed risk-relevant gene is expressed in oral periderm. The functional subsets of such SNPs are difficult to predict because the sequence underpinnings of periderm enhancers are unknown. We applied ATAC-seq to models of human palate periderm, including zebrafish periderm, mouse embryonic palate epithelia, and a human oral epithelium cell line, and to complementary mesenchymal cell types. We identified sets of enhancers specific to the epithelial cells and trained gapped-kmer support-vector-machine classifiers on these sets. We used the classifiers to predict the effect of 14 OFC-associated SNPs at 12q13 nearKRT18. All the classifiers picked the same SNP as having the strongest effect, but the significance was highest with the classifier trained on zebrafish periderm. Reporter and deletion analyses support this SNP as lying within a periderm enhancer regulatingKRT18/KRT8expression.
AERON: Transcript quantification and gene-fusion detection using long reads
Authors: Rautiainen Mikko , Durai Dilip A , Chen Ying , Xin Lixia , Low Hwee Meng , Göke Jonathan , Marschall Tobias , Schulz Marcel H. 
Published: January 2020

AbstractSingle-molecule sequencing technologies have the potential to improve measurement and analysis of long RNA molecules expressed in cells. However, analysis of error-prone long RNA reads is a current challenge. We present AERON for the estimation of transcript expression and prediction of gene-fusion events. AERON uses an efficient read-to-graph alignment algorithm to obtain accurate estimates for noisy reads. We demonstrate AERON to yield accurate expression estimates on simulated and real datasets. It is the first method to reliably call gene-fusion events from long RNA reads. Sequencing the K562 transcriptome, we used AERON and found known as well as novel gene-fusion events.
Environmental biases in the study of ecological networks at the planetary scale
Authors: Poisot Timothée , Bergeron Gabriel , Cazelles Kevin , Dallas Tad , Gravel Dominique , Macdonald Andrew , Mercier Benjamin , Violet Clément , Vissault Steve 
Published: January 2020

AbstractEcological networks are increasingly studied at large spatial scales, expanding their focus from a conceptual tool for community ecology into one that also adresses questions in biogeography and macroecology. This effort is supported by increased access to standardized information on ecological networks, in the form of openly accessible databases. Yet, there has been no systematic evaluation of the fitness for purpose of these data to explore synthesis questions at very large spatial scales. In particular, because the sampling of ecological networks is a difficult task, they are likely to not have a good representation of the diversity of Earth’s bioclimatic conditions, likely to be spatially aggregated, and therefore unlikely to achieve broad representativeness. In this paper, we analyze over 1300 ecological networks in the mangal.io database, and discuss their coverage of biomes, and the geographic areas in which there is a deficit of data on ecological networks. Taken together, our results suggest that while some information about the global structure of ecological networks is available, it remains fragmented over space, with further differences by types of eco-logical interactions. This causes great concerns both for our ability to transfer knowledge from one region to the next, but also to forecast the structural change in networks under climate change.
Antigenic variation by switching inter-chromosomal interactions with an RNA splicing locus in trypanosomes
Authors: Faria Joana , Luzak Vanessa , Müller Laura S.M. , Brink Benedikt G. , Hutchinson Sebastian , Glover Lucy , Horn David , Siegel T. Nicolai 
Published: January 2020

AbstractHighly selective gene expression is a key requirement for antigenic variation in several pathogens, allowing evasion of host immune responses and maintenance of persistent infections. African trypanosomes, parasites that cause lethal diseases in humans and livestock, employ an antigenic variation mechanism that involves monogenic antigen expression from a pool of >2500 antigen coding genes. In other eukaryotes, the expression of individual genes can be enhanced by mechanisms involving the juxtaposition of otherwise distal chromosomal loci in the three-dimensional nuclear space. However, trypanosomes lack classical enhancer sequences or regulated transcription initiation and the monogenic expression mechanism has remained enigmatic. Here, we show that the single expressed antigen coding gene displays a specific inter-chromosomal interaction with a major mRNA splicing locus. Chromosome conformation capture (Hi-C), revealed a dynamic reconfiguration of this inter-chromosomal interaction upon activation of another antigen. Super-resolution microscopy showed the interaction to be heritable and splicing dependent. We find that the two genomic loci are connected by the antigen exclusion complex, whereby VEX1 associated with the splicing locus and VEX2 with the antigen coding locus. Following VEX2 depletion, loss of monogenic antigen expression was accompanied by increased interactions between previously silent antigen genes and the splicing locus. Our results reveal a novel mechanism to ensure monogenic expression, requiring the spatial integration of antigen transcription and mRNA splicing in a dedicated compartment. These findings suggest a new means of post-transcriptional gene regulation.
Evaluation of DNA extraction protocols from liquid-based cytology specimens for studying cervical microbiota
Authors: Shibata Takeo , Nakagawa Mayumi , Coleman Hannah N. , Owens Sarah M. , Greenfield William W. , Sasagawa Toshiyuki , Robeson Michael S. 
Published: January 2020

AbstractCervical microbiota (CM) are considered an important factor affecting the progression of cervical intraepithelial neoplasia (CIN) and are implicated in the persistence of human papillomavirus (HPV). Collection of liquid-based cytology (LBC) samples is routine for cervical cancer screening and HPV genotyping and can be used for long-term cytological biobanking. We sought to determine whether it is possible to access microbial DNA from LBC specimens, and compared the performance of four different extraction protocols: (ZymoBIOMICS DNA Miniprep Kit; QIAamp PowerFecal Pro DNA Kit; QIAamp DNA Mini Kit; and IndiSpin Pathogen Kit) and their ability to capture the diversity of CM from LBC specimens. LBC specimens from 20 patients (stored for 716 ± 105 days) with CIN values of 2 or 3 were each aliquoted for each of the four kits. Loss of microbial diversity due to long-term LBC storage could not be assessed due to lack of fresh LBC samples. Comparisons with other types of cervical sampling were not performed. We observed that all DNA extraction kits provided equivalent accessibility to the cervical microbial DNA within stored LBC samples. Approximately 80% microbial genera were shared among all DNA extraction protocols. Potential kit contaminants were observed as well. Variation between individuals was a significantly greater influence on the observed microbial composition than was the method of DNA extraction. We also observed that HPV16 was significantly associated with community types that were not dominated byLactobacillus iners.
Nelfinavir was predicted to be a potential inhibitor of 2019-nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation
Authors: Xu Zhijian , Peng Cheng , Shi Yulong , Zhu Zhengdan , Mu Kaijie , Wang Xiaoyu , Zhu Weiliang 
Published: January 2020

Abstract2019-nCov has caused more than 80 deaths as of 27 January 2020 in China, and infection cases have been reported in more than 10 countries. However, there is no approved drug to treat the disease. 2019-nCov Mprois a potential drug target to combat the virus. We built homology models based on SARS Mprostructures, and docked 1903 small molecule drugs to the models. Based on the docking score and the 3D similarity of the binding mode to the known Mproligands, 4 drugs were selected for binding free energy calculations. Both MM/GBSA and SIE methods voted for nelfinavir, with the binding free energy of −24.69±0.52 kcal/mol and −9.42±0.04 kcal/mol, respectively. Therefore, we suggested that nelfinavir might be a potential inhibitor against 2019-nCov Mpro.
A paralog-specific role of the COPI pathway in the neuronal differentiation of murine pluripotent cells
Authors: Goyal Manu , Zhao Xiyan , Bozhinova Mariya , Andrade López Karla Lisette , de Heus Cecilia , Schulze-Dramac Sandra , Müller-McNicoll Michaela , Klumperman Judith , Béthune Julien 
Published: January 2020

ABSTRACTCoat protein complex I (COPI)-coated vesicles mediate membrane trafficking between Golgi cisternae as well as retrieval of proteins from the Golgi to the endoplasmic reticulum. There are several flavors of the COPI coat defined by paralogous subunits of the protein complex coatomer. However, whether paralogous COPI proteins have specific functions is currently unknown. Here we show that the paralogous coatomer subunits γ1-COP and γ2-COP are differentially expressed during the neuronal differentiation of mouse pluripotent cells. Moreover, through a combination of genome editing experiments, we demonstrate that whereas γ-COP paralogs are largely functionally redundant, γ1-COP specifically promotes neurite outgrowth. Our work stresses a role of the COPI pathway in neuronal polarization and provides evidence for distinct functions for coatomer paralogous subunits in this process.