bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic regulation of differentially expressed genes between various glioma types
Authors: Grabowicz Ilona E. , Wilczyński Bartek , Kamińska Bożena , Roura Adria-Jaume , Wojtaś Bartosz , Dąbrowski Michał J. 
Published: August 2020

AbstractGliomas are the most frequent primary tumors of the central nervous system (CNS) and encompass two major subgroups: diffuse, malignant gliomas and benign, well differentiated gliomas showing a more circumscribed growth. Genome-wide next generation sequencing studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different types of gliomas improving tumor diagnosis and having important implications for future clinical trials and patient management. We have recently created a unique resource encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we took advantage of a wealth of data from those high-throughput experiments, intersected those data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found a set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing glioma-related genes. Moreover, many genes associated with the cell-matrix adhesion Gene Ontology group, in particular 14PROTOCADHERINs, were found to be regulated by the long range contacts with enhancers. Overall, the results presented here demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy. We demonstrated that integration of whole genome epigenetic data with Hi-C data and transcriptomic profiles described in this work, can segregate low and high grade gliomas and reveal new regulatory networks that could explain some of the functional differences between gliomas of different malignancies.HighlightsIntegration of ATAC-seq, ChIP-seq and RNA-seq reveals glioma malignancy-related gene regulatory networks.TADs segmentation contributes to gene-epigenetically modified enhancer relationships.Contacts of active enhancers in gliomas of different malignancies might affect expression of genes involved in cancerogenesis, such asPROTOCADHERINsorEGFR.
Real-time single-cell characterization of the eukaryotic transcription cycle reveals correlations between RNA initiation, elongation, and cleavage
Authors: Liu Jonathan , Hansen Donald , Eck Elizabeth , Kim Yang Joon , Turner Meghan , Alamos Simon , Garcia Hernan G. 
Published: August 2020

AbstractThe eukaryotic transcription cycle consists of three main steps: initiation, elongation, and cleavage of the nascent RNA transcript. Although each of these steps can be regulated as well as coupled with each other, theirin vivodissection has remained challenging because available experimental readouts lack sufficient spatiotemporal resolution to separate the contributions from each of these steps. Here, we describe a novel application of Bayesian inference techniques to simultaneously infer the effective parameters of the transcription cycle in real time and at the single-cell level using a two-color MS2/PP7 reporter gene and the developing fruit fly embryo as a case study. Our method enables detailed investigations into cell-to-cell variability in transcription-cycle parameters as well as single-cell correlations between these parameters. These measurements, combined with theoretical modeling, suggest a substantial variability in the elongation rate of individual RNA polymerase molecules. We further illustrate the power of this technique by uncovering a novel mechanistic connection between RNA polymerase density and nascent RNA cleavage efficiency. Thus, our approach makes it possible to shed light on the regulatory mechanisms in play during each step of the transcription cycle in individual, living cells at high spatiotemporal resolution.
Expansion Revealing: Decrowding Proteins to Unmask Invisible Brain Nanostructures
Authors: Sarkar Deblina , Kang Jinyoung , Wassie Asmamaw T , Schroeder Margaret E. , Peng Zhuyu , Tarr Tyler B. , Tang Ai-Hui , Niederst Emily , Young Jennie. Z. , Tsai Li-Huei , Blanpied Thomas A. , Boyden Edward S. 
Published: August 2020

AbstractCells and tissues are made out of nanoscale building blocks, such as proteins, organized in crowded nanostructures. We show that many biomolecules, and the nanostructures in which they are embedded, may be invisible to prior imaging techniques, due to the inaccessibility of labels (e.g., antibodies) to biomolecules embedded within such crowded structures. We developed a technology, expansion revealing (ExR), which isotropically decrowds proteins from each other, to enable their labeling. We use ExR to discover the alignment of presynaptic calcium channels with postsynaptic machinery in intact brain circuits, as well as the existence of periodic amyloid nanoclusters containing ion channel proteins in Alzheimer’s model mice. Thus, ExR reveals nanostructures within complex biological specimens that were not previously visualizable, and may find broad use in biology.One Sentence SummaryDe-crowding biomolecules with Expansion Revealing unmasks fundamentally new nanostructures in intact brain tissue, which remained invisible otherwise.
The subcellular architecture of thexylgene expression flow of the TOL catabolic plasmid ofPseudomonas putidamt-2
Authors: Kim Juhyun , Goñi-Moreno Angel , de Lorenzo Víctor 
Published: August 2020

ABSTRACTDespite intensive research on the biochemical and regulatory features of the archetypal catabolic TOL system borne by pWW0 ofPseudomonas putidamt-2, the physical arrangement and tridimensional logic of thexylgene expression flow remains unknown. In this work, the spatial distribution of specificxylmRNAs with respect to the host nucleoid, the TOL plasmid and the ribosomal pool has been investigated.In situhybridization of target transcripts with fluorescent oligonucleotide probes revealed thatxylmRNAs cluster in discrete foci, adjacent but clearly separated from the TOL plasmid and the cell nucleoid. Also, they co-localize with ribosome-rich domains of the intracellular milieu. This arrangement was kept even when thexylgenes were artificially relocated at different chromosomal locations. The same happened when genes were expressed through a heterologous T7 polymerase-based system, which originated mRNA foci outside the DNA. In contrast, rifampicin treatment, known to ease crowding, blurred the confinement ofxyltranscripts. This suggested thatxylmRNAs intrinsically run away from their initiation sites to ribosome-rich points for translation—rather than being translated coupled to transcription. Moreover, the results suggest that the distinct subcellular motion ofxylmRNAs results both from innate properties of the sequence at stake and the physical forces that keep the ribosomal pool away from the nucleoid inP. putida. This scenario is discussed on the background of current knowledge on the 3D organization of the gene expression flow in other bacteria and the environmental lifestyle of this soil microorganism.IMPORTANCEThe transfer of information between DNA, RNA and proteins in a bacterium is often compared to the decoding of a piece of software in a computer. However, the tridimensional layout and the relational logic of the cognate biological hardware i.e. the nucleoid, the RNA polymerase and the ribosomes, are habitually taken for granted. In this work we inspected the localization and fate of the transcripts that stem from the archetypal biodegradative plasmid pWW0 of soil bacteriumPseudomonas putidaKT2440 through the non-homogenous milieu of the bacterial cytoplasm. The results expose that— similarly to computers also—the material components that enable the expression flow are well separated physically and they decipher the sequences through a distinct tridimensional arrangement with no indication of transcription/translation coupling. We argue that the resulting subcellular architecture enters an extra regulatory layer that obeys a species-specific positional code that accompanies the environmental lifestyle of this bacterium.
Homeotic Regulation of Olfactory Receptor Choice via NFI-dependent Heterochromatic Silencing and Genomic Compartmentalization
Authors: Bashkirova Elizaveta , Monahan Kevin , Campbell Christine E. , Osinski Jason M. , Tan Longzhi , Schieren Ira , Barnea Gilad , Xie X. Sunnie , Gronostajski Richard M. , Lomvardas Stavros 
Published: August 2020

AbstractExpression of one out of >1000 olfactory receptor (OR) genes is stochastic but, yet, spatially organized in stereotypic anatomical segments, or “zones”, along the dorsoventral axis of the mouse olfactory epithelium. We discovered that zonal OR expression is specified by OR chromatin structure and genome architecture during olfactory neuron differentiation. Specifically, across every zone dorsally expressed ORs have higher levels of heterochromatic marks and long-range contacts than ORs expressed ventrally. However, OR heterochromatin levels and frequency of genomic contacts between ORs gradually increase towards ventral zones. Consequently, ORs from dorsal indexes accumulate high H3K9me3/H3K79me3 enrichment and become silenced in ventral zones, while ORs from ventral indexes lack activating long-range genomic interactions and, thus, cannot be chosen in dorsal segments. This process is regulated by NFIA, B, and X gradients along the dorsoventral axis, triple deletion of which causes homeotic transformations on zonal OR expression, heterochromatin formation, and genomic compartmentalization.
The nucleocytosolicO-fucosyltransferaseSpindlyaffects protein expression and virulence inToxoplasma gondii
Authors: Bandini Giulia , Agop-Nersesian Carolina , van der Wel Hanke , Mandalasi Msano , Kim Hyunwoo , West Christopher M. , Samuelson John 
Published: August 2020

AbstractOnce considered unusual, nucleocytoplasmic glycosylation is now recognized as a conserved feature of eukaryotes. While in animalsO-GlcNAc transferase (OGT) modifies thousands of intracellular proteins, the human pathogenToxoplasma gondiitransfers a different sugar, fucose, to proteins involved in transcription, mRNA processing and signaling. Knockout experiments showed thatTgSPY, an ortholog of plant SPINDLY and paralog of host OGT, is required for nuclearO-fucosylation. Here we verify thatTgSPY is the nucleocytoplasmicO-fucosyltransferase (OFT) by 1) complementation withTgSPY-MYC3, 2) its functional dependence on amino acids critical for OGT activity, and 3) its ability toO-fucosylate itself and a model substrate and to specifically hydrolyze GDP-Fuc. While many of the endogenous proteins modified byO-Fuc are important for tachyzoite fitness,O-fucosylation byTgSPY is not essential. Growth of Δspytachyzoites in fibroblasts is modestly affected, despite marked reductions in the levels of ectopically-expressed proteins normally modified withO-fucose. IntactTgSPY-MYC3localizes to the nucleus and cytoplasm, whereas catalytic mutants often displayed reduced abundance. Δspytachyzoites of a luciferase-expressing type II strain exhibited infection kinetics in mice similar to wild type but increased persistence in the chronic brain phase, potentially due to an imbalance of regulatory protein levels. The modest changes in parasite fitnessin vitroand in mice, despite profound effects on reporter protein accumulation, and the characteristic punctate localization ofO-fucosylated proteins, suggest thatTgSPY controls the levels of proteins to be held in reserve for response to novel stresses.
Identifying seaweeds species of Chlorophyta, Phaeophyta and Rhodophyta using DNA barcodes
Authors: Prasanthi Narra , Prasannakumar Chinnamani , Annadurai D. , Mahendran S. , Mohammed Alshehri A. H. 
Published: August 2020

AbstractStrengthening the DNA barcode database is important for a species level identification, which was lacking for seaweeds. We made an effort to collect and barcode seaweeds occurring along Southeast coast of India. We barcoded 31 seaweeds species belonging to 21 genera, 14 family, 12 order of 3 phyla (viz., Chlorophyta, Phaeophyta and Rhodophyta). We found 10 species in 3 phyla and 2 genera (AnthophycusandChnoospora) of Phaeophyta were barcoded for the first time. Uncorrected p-distance calculated using K2P, nucleotide diversity and Tajima’s test statistics reveals highest values among the species of Chlorophyta. Over all K2P distance was 0.36. The present study revealed the potentiality of rbcL gene sequences in identification of all 3 phyla of seaweeds. We also found that the present barcode reference libraries (GenBank and BOLD) were insufficient in seaweeds identification and more efforts were needed for strengthening local seaweed barcode library to benefit rapids developing field such as environmental DNA barcoding. We also show that the constructed barcode library could aid various industrial experts involved in seaweed bio-resource exploration and taxonomy/non-taxonomic researches involved in climate, agriculture and epigenetics research in precise seaweed identification. Since the rise of modern high-throughput sequencing technologies is significantly altering bio-monitoring applications and surveys, reference datasets such as ours will become essential in ecosystem’s health assessment and monitoring.
Identification of novel avian and mammalian deltaviruses provides new insights into deltavirus evolution
Authors: Iwamoto Masashi , Shibata Yukino , Kawasaki Junna , Kojima Shohei , Li Yung-Tsung , Iwami Shingo , Muramatsu Masamichi , Wu Hui-Lin , Wada Kazuhiro , Tomonaga Keizo , Watashi Koichi , Horie Masayuki 
Published: August 2020

AbstractHepatitis delta virus (HDV) is a satellite virus that requires hepadnavirus envelope proteins for its transmission. Although recent studies identified HDV-related deltaviruses in certain animals, the evolution of deltaviruses, such as the origin of HDV and the mechanism of its coevolution with its helper viruses, is unknown, mainly because of the phylogenetic gaps among deltaviruses. Here we identified novel deltaviruses of passerine birds, woodchucks, and white-tailed deer by extensive database searches and molecular surveillance. Phylogenetic and molecular epidemiological analyses suggest that HDV originated from mammalian deltaviruses and the past interspecies transmission of mammalian and passerine deltaviruses. Further, metaviromic and experimental analyses suggest that the satellite-helper relationship between HDV and hepadnavirus was established after the divergence of the HDV lineage from non-HDV mammalian deltaviruses. Our findings enhance our understanding of deltavirus evolution, diversity, and transmission, indicating the importance of further surveillance for deltaviruses.
The Formin Inhibitor, SMIFH2, Inhibits Members of the Myosin Superfamily
Authors: Nishimura Yukako , Shi Shidong , Zhang Fang , Liu Rong , Takagi Yasuharu , Bershadsky Alexander D. , Viasnoff Virgile , Sellers James R. 
Published: August 2020

AbstractThe small molecular inhibitor of formin FH2 domains, SMIFH2, is widely used in cell biological studies. It was selected in a chemical screen as a compound inhibiting formin-driven actin polymerizationin vitro, but not polymerization of pure actin, and found to be active against several types of formins from different species (Rizvi et al., 2009). Here, in experiments with cultured fibroblasts, we found that SMIFH2 inhibits retrograde flow of myosin 2 filaments and contraction of stress fibers. We further checked the effect of SMIFH2 on non-muscle myosin 2A and skeletal muscle myosin 2in vitroand found that SMIFH2 inhibits myosin ATPase activity and ability to translocate actin filaments in thein vitromotility assay. While inhibition of myosin 2Ain vitrorequired somewhat higher concentration of SMIFH2 than inhibition of retrograde flow and stress fiber contraction in cells, inhibition of several other non-muscle myosin types, e.g. mammalian myosin 10,Drosophilamyosin 7a andDrosophilamyosin 5 by SMIFH2, was equally or more efficient than inhibition of formins. Since actin polymerization and myosin contractility are linked in many cytoskeleton processes, additional careful analysis is needed in each case when function of formins was proposed solely on the basis of experiment with SMIFH2.
A novel SHAPE reagent enables the analysis of RNA structure in living cells with unprecedented accuracy
Authors: Marinus Tycho , Fessler Adam B. , Ogle Craig A. , Incarnato Danny 
Published: August 2020

ABSTRACTDue to the mounting evidence that RNA structure plays a critical role in regulating almost any physiological as well as pathological process, being able to accurately define the folding of RNA molecules within living cells has become a crucial need. We introduce here 2-aminopyridine-3-carboxylic acid imidazolide (2A3), as a general probe for the interrogation of RNA structuresin vivo. 2A3 shows moderate improvements with respect to the state-of-the-art SHAPE reagent NAI on naked RNA underin vitroconditions, but it significantly outperforms NAI when probing RNA structurein vivo, particularly in bacteria, underlining its increased ability to permeate biological membranes. When used as a restraint to drive RNA structure prediction, data derived by SHAPE-MaP with 2A3 yields more accurate predictions than NAI-derived data. Due to its extreme efficiency and accuracy, we can anticipate that 2A3 will rapidly take over conventional SHAPE reagents for probing RNA structures bothin vitroandin vivo.
The labour disputes of Chinese posted workers in the B&R countries
Authors: Yan Dong , Wu Yixuan 
Published: August 2020

PurposeThis study aims to decrypt the efforts made by Chinese people's courts nationwide to protect the rights of Chinese posted workers in the Belt & Road (B&R) countries by investigating labour litigation cases with an extraterritorial application of Chinese labour law (under the “doctrine of overriding mandatory labour rules”).Design/methodology/approachThis study collected all labour litigation from 2014 to 2018 brought forward by Chinese posted workers in Chinese courts against Chinese enterprises regarding the performance of employment contracts in the B&R countries where Chinese labour laws were mandatorily applied under the doctrine of overriding mandatory labour rules. The study adopted a qualitive research approach to analyse the compiled cases to explore their characteristics and effects.FindingsThis study found that the volume of labour disputes in the B&R countries had a somewhat positive correlation to the amount of investment from China. However, this correlation was rather superficial when compared with the correlation to the type of industrial sector (e.g. the construction sector) and to the claim category (e.g. remuneration claims). Moreover, labour disputes in both the B&R countries and China shared a great deal of similarity with regard to their concentration in certain sectors and in certain types of claims. Therefore, mandatorily applying Chinese labour law could be convenient for Chinese workers returning from abroad who seek remedies and could allow Chinese judges to issue affirmative decisions regardless of the territory in which the worker was posted.Research limitations/implicationsThe cases collected by this study were limited to those filed in China by Chinese workers who were hired by Chinese enterprises and sent to work in the B&R countries and did not include those filed in the B&R countries by Chinese posted workers. Future research should therefore attempt to gather a broader range of labour disputes to further clarify the issues and need for labour protection for Chinese posted workers in the B&R countries.Practical implicationsThis study argues that the doctrine of overriding mandatory labour rules is not entirely unproblematic because it might arbitrarily rule out the standards set by foreign labour legislation that could be more favourable to workers or offer them greater protection. Therefore, giving judges a certain degree of discretion is imperative to allow them to apply foreign labour standards when they have been proven to benefit workers.Originality/valueApart from a handful of reports on individual cases, there have been very few empirical studies regarding the general picture of labour protection for Chinese posted workers in the B&R countries. This study has adopted a novel approach to collect information on labour disputes in the B&R countries and to facilitate a qualitative analysis to test the practical implications of the doctrine of overriding mandatory labour rules.
An empirical examination of the antecedents of training transfer in hotels: the moderating role of supervisor support
Authors: El-Said Osman Ahmed , Al Hajri Bashaer , Smith Michael 
Published: August 2020

PurposeCurrently, the global hotel industry is faced with the challenge of a growing skills gap. Contrary to expectations, the shortage of skilled employees persists despite improved access to training. This implies that the cause of the shortage is not the lack of training, but a general lack of understanding of how training is transferred to practice. Therefore, this study aims to use an empirical approach to test a transfer of training (TOT) model that can be applied to the hotel sector.Design/Methodology/ApproachThe setting of the study is the Sultanate of Oman, and 302 questionnaires were collected from 24 hotel properties, of four- and five-star categories.FindingsThe findings reveal, to a high and significant degree, that the antecedents of TOT are the opportunity to perform (OTP) and motivation to transfer (MTT), while supervisor support is a significant moderator. In addition, motivation to learn (MTL) is the most important predictor of MTT, while accountability is the leading predictor of OTP. Results also indicated that perceived organizational support (OS) has the strongest impact on MTL.Research Limitations ImplicationsThe proposed model needs to be tested under different contexts, especially different countries and with different hotel categories, to determine if the relationships between the factors remain similarly valid. Other factors that can predict the TOT need to be investigated.Practical ImplicationsPractical recommendations for hotel operators have been presented, equipping industry practitioners with the tools they need to develop the competencies of their employees, thereby improving the performance of individual properties.Originality ValueThe current study emphasized the validity of the proposed training transfer framework which was adapted from the learning transfer system inventory model, highlighting the particular importance of factors such as perceived OS and accountability.