bluuebunny/crossref_metadata_2025_split huggingface dataset:
In plants distal regulatory sequences overlap with unmethylated rather than low-methylated regions, in contrast to mammals
Authors: Oka Rurika , Bliek Mattijs , Hoefsloot Huub C.J. , Stam Maike 
Published: March 2020

AbstractBackgroundDNA methylation is an important factor in the regulation of gene expression and genome stability. High DNA methylation levels are associated with transcriptional repression. In mammalian systems, unmethylated, low methylated and fully methylated regions (UMRs, LMRs, and FMRs, respectively) can be distinguished. UMRs are associated with proximal regulatory regions, while LMRs are associated with distal regulatory regions. Although DNA methylation is mainly limited to the CG context in mammals, while it occurs in CG, CHG and CHH contexts in plants, UMRs and LMRs were expected to occupy similar genomic sequences in both mammals and plants.ResultsThis study investigated major model and crop plants such asArabidopsis thaliana, tomato (Solanum lycopersicum), rice (Oryza sativa) and maize (Zea mays), and shows that plant genomes can also be subdivided in UMRs, LMRs and FMRs, but that LMRs are mainly present in the CHG context rather than the CG context. Strikingly, the identified CHG LMRs were enriched in transposable elements rather than regulatory regions. Maize candidate regulatory regions overlapped with UMRs. LMRs were enriched for heterochromatic histone modifications and depleted for DNase accessibility and H3K9 acetylation. CHG LMRs form a distinct, abundant cluster of loci, indicating they have a different role than FMRs.ConclusionsBoth mammalian and plant genomes can be segmented in three distinct classes of loci, UMRs, LMRs and FMRs, indicating similar underlying mechanisms. Unlike in mammals, distal regulatory sequences in plants appear to overlap with UMRs instead of LMRs. Our data indicate that LMRs in plants have a different function than those in mammals.
mir-21 is associated with inactive low molecular weight Argonaute complexes in thyroid cancer cell lines
Authors: Powell Bonita H. , Turchinovich Andrey , Wang Yongchun , Liao Zhaohao , Dar Mohammad Aasif , Rocca Gaspare La , Umanah George Essien , Zeiger Martha A. , Umbricht Christopher B. , Witwer Kenneth W. 
Published: March 2020

ABSTRACTThyroid cancer is the most prevalent endocrine malignancy. We and others have shown that several microRNAs, which are post-transcriptional gene regulators, are aberrantly expressed in anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) tissues, as well as cell lines derived from these cancers. In the cell, miRNAs are bound to Argonaute (AGO) proteins as what could be termed low molecular weight RNA-Induced Silencing Complexes (LMW-RISCs) that can assemble with additional proteins, mRNA, and translation machinery into high molecular weight RISCs (HMW-RISCs) that exert regulatory function. In this study, we sought to analyze the association of miRNAs with RISC complexes in ATC and PTC. For ATC and PTC lines, miRNA species were enriched in both HMW-RISC and LMW-RISC cellular fractions, compared with intermediate molecular weight fractions and very low molecular weight (AGO-poor) fractions. Furthermore, 60% of all miRNAs were slightly more abundant in LMW-RISC versus HMW-RISC fractions by ~2-4 fold. Surprisingly, miR-21-5p, one of the most abundant miRNAs in both ATC and PTC lines and one of the most widely studied oncogenic miRNAs in many solid tumors, was consistently one the least abundant miRNAs in HMW-RISC and the most enriched miRNA in LMW-RISC fractions. These findings may suggest that miR-21 has a role or roles distinct from canonical post-transcriptional regulation in cancer. Furthermore, the methodology described here is a useful way to assess the distribution of miR-21 between HMW and LMW-RISCs and may help to reveal the true roles of this miRNA in thyroid cancer development, progression, and treatment.
Open source software tool for the automated detection and characterization of epithelial cells from trace biological samples
Authors: Olsen Anita , Miller Mekhi , Yadavalli Vamsi K. , Ehrhardt Christopher J. 
Published: March 2020

AbstractThis paper presents a strategy for an unsupervised workflow for identifying epithelial cells in microscopic images and characterizing their morphological and/or optical properties. The proposed method can be used on cells that have been stained with fluorescent dyes and imaged using conventional optical microscopes. The workflow was tested on cell populations that were imaged directly on touch/contact surfaces and stained with nucleic acid dyes to visualize genetic content. Our results show that this approach could be a useful strategy for characterizing differences in staining efficiency and/or morphological properties of individual cells or aggregate populations within a biological sample. Further, they can potentially reduce the laborious nature of microscopic analysis and increase throughput and reproducibility of similar studies.
Effects of cell cycle variability on lineage and population measurements of mRNA abundance
Authors: Perez-Carrasco Ruben , Beentjes Casper , Grima Ramon 
Published: March 2020

AbstractMany models of gene expression do not explicitly incorporate a cell cycle description. Here we derive a theory describing how mRNA fluctuations for constitutive and bursty gene expression are influenced by stochasticity in the duration of the cell cycle and the timing of DNA replication. Analytical expressions for the moments show that omitting cell cycle duration introduces an error in the predicted mean number of mRNAs that is a monotonically decreasing function ofη, which is proportional to the ratio of the mean cell cycle duration and the mRNA lifetime. By contrast, the error in the variance of the mRNA distribution is highest for intermediate values ofηconsistent with genome-wide measurements in many organisms. Using eukaryotic cell data, we estimate the errors in the mean and variance to be at most 3% and 25%, respectively. Furthermore, we derive an accurate negative binomial mixture approximation to the mRNA distribution. This indicates that stochasticity in the cell cycle can introduce fluctuations in mRNA numbers that are similar to the effect of bursty transcription. Finally, we show that for real experimental data, disregarding cell cycle stochasticity can introduce errors in the inference of transcription rates larger than 10%.
Layered Feedback Control Improves Robust Functionality across Heterogeneous Cell Populations
Authors: Ren Xinying , Murray Richard M. 
Published: March 2020

AbstractRealizing homeostatic control of metabolites or proteins is one of the key goals of synthetic circuits. However, if control is only implemented internally in individual cells, cell-cell heterogeneity may break the homeostasis on population level since cells do not contribute equally to the production or regulation. New control structures are needed to achieve robust functionality in heterogeneous cell populations. Quorum sensing (QS) serves as a collective mechanism by releasing and sensing small and diffusible signaling molecules for group decision-making. We propose a layered feedback control structure that includes a global controller using quorum sensing and a local controller via internal signal-receptor systems. We demonstrate with modeling and simulation that the global controller drives contributing cells to compensate for disturbances while the local controller governs the fail-mode performance in non-contributing cells. The layered controller can tolerate a higher portion of non-contributing cells or longer generations of mutant cells while maintaining metabolites or proteins level within a small error range, compared with only internal feedback control. We further discuss the potential of such layered structures in robust control of cell population size, population fraction and other population-dependent functions.
Structure and mechanism of potent bifunctional β-lactam- and homoserine lactone-degrading enzymes from marine microorganisms
Authors: Selleck Christopher , Pedroso Marcelo Monteiro , Wilson Liam , Krco Stephan , Knaven Esmée Gianna , Miraula Manfredi , Mitić Nataša , Larrabee James A. , Brück Thomas , Clark Alice , Guddat Luke W. , Schenk Gerhard 
Published: March 2020

AbstractGenes that confer antibiotic resistance can rapidly be disseminated from one microorganism to another by mobile genetic elements, thus transferring resistance to previously susceptible bacterial strains. The misuse of antibiotics in health care and agriculture has provided a powerful evolutionary pressure to accelerate the spread of resistance genes, including those encoding β-lactamases. These are enzymes that are highly efficient in inactivating most of the commonly used β-lactam antibiotics. However, genes that confer antibiotic resistance are not only associated with pathogenic microorganisms, but are also found in non-pathogenic (i.e. environmental) microorganisms. Two recent examples are metal-dependent β-lactamases (MBLs) from the marine organismsNovosphingobium pentaromativoransandSimiduia agarivorans. Previous studies have demonstrated that their β-lactamase activity is comparable to those of well-known MBLs from pathogenic sources (e.g. NDM-1, AIM-1) but that they also possess efficient lactonase activity, an activity associated with quorum sensing. Here, we probed the structure and mechanism of these two enzymes using crystallographic, spectroscopic and fast kinetics techniques. Despite highly conserved active sites both enzymes demonstrate significant variations in their reaction mechanisms, highlighting both the extraordinary ability of MBLs to adapt to changing environmental conditions and the rather promiscuous acceptance of diverse substrates by these enzymes.
Integrated analysis of a compendium of RNA-Seq datasets for splicing factors
Authors: Yu Peng , Li Jin , Deng Su-Ping , Zhang Feiran , Grozdanov Petar N. , Chin Eunice W. M. , Martin Sheree D. , Vergnes Laurent , Islam M. Saharul , Sun Deqiang , LaSalle Janine M. , McGee Sean L. , Goh Eyleen , MacDonald Clinton C. , Jin Peng 
Published: March 2020

AbstractA vast amount of public RNA-sequencing datasets have been generated and used widely to study transcriptome mechanisms. These data offer precious opportunity for advancing biological research in transcriptome studies such as alternative splicing. We report the first large-scale integrated analysis of RNA-Seq data of splicing factors for systematically identifying key factors in diseases and biological processes. We analyzed 1,321 RNA-Seq libraries of various mouse tissues and cell lines, comprising more than 6.6 TB sequences from 75 independent studies that experimentally manipulated 56 splicing factors. Using these data, RNA splicing signatures and gene expression signatures were computed, and signature comparison analysis identified a list of key splicing factors in Rett syndrome and cold-induced thermogenesis. We show that cold-induced RNA-binding proteins rescue the neurite outgrowth defects in Rett syndrome using neuronal morphology analysis, and we also reveal that SRSF1 and PTBP1 are required for energy expenditure in adipocytes using metabolic flux analysis. Our study provides an integrated analysis for identifying key factors in diseases and biological processes and highlights the importance of public data resources for identifying hypotheses for experimental testing.
Transcriptome-Wide Combinatorial RNA Structure Probing in Living Cells
Authors: Chan Dalen , Feng Chao , England Whitney , Wyman Dana , Flynn Ryan A. , Wang Xiuye , Shi Yongsheng , Mortazavi Ali , Spitale Robert C. 
Published: March 2020

AbstractRNA molecules can fold into complex structures and interact with trans-acting factors to control their biology. Recent methods have been focused on developing novel tools to measure RNA structure transcriptome-wide, but their utility to study and predict RNA-protein interactions or RNA processing has been limited thus far. Here, we extend these studies with the first transcriptomewide mapping method for cataloging RNA solvent accessibility, icLASER. By combining solvent accessibility (icLASER) with RNA flexibility (icSHAPE) data, we efficiently predict RNA-protein interactions transcriptome-wide and catalog RNA polyadenylation sites by RNA structure alone. These studies showcase the power of designing novel chemical approaches to studying RNA biology. Further, our study exemplifies merging complementary methods to measure RNA structure inside cells and its utility for predicting transcriptome-wide interactions that are critical for control of and regulation by RNA structure. We envision such approaches can be applied to studying different cell types or cells under varying conditions, using RNA structure and footprinting to characterize cellular interactions and processing involving RNA.
Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism
Authors: Liu Qi , Gupta Amita , Okesli-Armlovich Ayse , Qiao Wenjie , Fischer Curt R. , Smith Mark , Carette Jan E. , Bassik Michael C. , Khosla Chaitan 
Published: March 2020

AbstractGenome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase (DHODH) as its target, along with the discovery that knockdown of genes in pyrimidine salvage pathways sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was efficiently converted into its triphosphates in cells. When combined with GSK983, it led to large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral genome infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activities of RdRp inhibitors.
First synthesis of a unique icosahedral phase from the Khatyrka meteorite by shock-recovery experiment
Authors: Hu Jinping , Asimow Paul D. , Ma Chi , Bindi Luca 
Published: March 2020

Icosahedral quasicrystals (i-phases) in the Al–Cu–Fe system are of great interest because of their perfect quasicrystalline structure and natural occurrences in the Khatyrka meteorite. The natural quasicrystal of composition Al62Cu31Fe7, referred to as i-phase II, is unique because it deviates significantly from the stability field of i-phase and has not been synthesized in a laboratory setting to date. Synthetic i-phases formed in shock-recovery experiments present a novel strategy for exploring the stability of new quasicrystal compositions and prove the impact origin of natural quasicrystals. In this study, an Al–Cu–W graded density impactor (GDI, originally manufactured as a ramp-generating impactor but here used as a target) disk was shocked to sample a full range of Al/Cu starting ratios in an Fe-bearing 304 stainless-steel target chamber. In a strongly deformed region of the recovered sample, reactions between the GDI and the steel produced an assemblage of co-existing Al61.5Cu30.3Fe6.8Cr1.4 i-phase II + stolperite (β, AlCu) + khatyrkite (θ, Al2Cu), an exact match to the natural i-phase II assemblage in the meteorite. In a second experiment, the continuous interface between the GDI and steel formed another more Fe-rich quinary i-phase (Al68.6Fe14.5Cu11.2Cr4Ni1.8), together with stolperite and hollisterite (λ, Al13Fe4), which is the expected assemblage at phase equilibrium. This study is the first laboratory reproduction of i-phase II with its natural assemblage. It suggests that the field of thermodynamically stable icosahedrite (Al63Cu24Fe13) could separate into two disconnected fields under shock pressure above 20 GPa, leading to the co-existence of Fe-rich and Fe-poor i-phases like the case in Khatyrka. In light of this, shock-recovery experiments do indeed offer an efficient method of constraining the impact conditions recorded by quasicrystal-bearing meteorite, and exploring formation conditions and mechanisms leading to quasicrystals.
Do high-performance work systems mediate the relationship between HR practices and employee performance in multinational corporations (MNCs) in developing economies?
Authors: Abugre James Baba , Nasere David 
Published: March 2020

PurposeThe purpose of this paper is to examine the mediating role of job involvement as high-performance work system (HPWS) on the relationship between human resource (HR) practices and employee performance in multinational corporations (MNCs) in developing economies using Ghana as a case study.Design/methodology/approachUsing questionnaires to collect data from 317 employees and ten MNCs in Ghana, structural equation modeling (SEM), multiple regression and bootstrapping analysis were used to analyze the data.FindingsThe results showed that an HPWS proxy as job involvement fully mediates the relationship between HR practices and employee performance. The findings also showed that training and development and compensation and reward have a significant and direct positive effect on employee performance.Practical implicationsThis paper provides a practical guide to management and corporations on the significance of training and compensation on employee performance in MNCs. The study, therefore, recommends managers of firms and corporations to take a serious look at their HR practices and institute an HPWS, which can positively improve both corporate and employee performance.Originality/valueThis paper enhances our understanding of micro-level HPWS in the form of job involvement as a positive mediator between training and development and employee performance on the one hand, and between compensation and reward and employee performance on the other hand in work organizations in a less-studied context.
The joint production of confidence – self-regulation in European crowdfunding markets
Authors: Odorović Ana , Wenzlaff Karsten 
Published: March 2020

PurposeThe paper discusses the rationale for a widespread reliance on Codes of Conduct (CoC) in European crowdfunding through the lenses of economic theories of self-regulation. By analysing the institutional design of CoCs in crowdfunding, the paper illustrates the differences in their regulatory context, inclusiveness, monitoring and enforcement. It offers the first systematic overview of substantial rules of CoCs in crowdfunding.Design/methodology/approachA comparative case study of nine CoCs in Europe is used to illustrate differences in their institutional design and discern the economic purpose of the CoC.FindingsThe institutional design of different CoCs in Europe mainly supports voluntary theories of self-regulation. In particular, the theory of reputation commons has the most explanatory power. The substantial rules of CoC in different markets show the potential sources of market failure through the perspectives of platforms.Research limitations/implicationsCoCs appear in various regulatory, cultural, and industry contexts of different countries. Some of the institutional design features of CoC might be a result of these characteristics.Practical implicationsCrowdfunding associations wishing to develop their own CoC may learn from a comparative overview of key provisions.Social implicationsFor governments in Europe, contemplating creating or revising bespoke crowdfunding regimes, the paper identifies areas where crowdfunding platforms perceive market failure.Originality/valueThis paper is the first systematic study of self-regulatory institutions in European crowdfunding. The paper employs a theoretical framework for the analysis of self-regulation in crowdfunding and provides a comparison of a regulatory context, inclusiveness, monitoring and enforcement of different CoCs in Europe.
Impact of personal and organizational factors on knowledge sharing attitude of university teachers in Pakistan
Authors: Javaid Javaria , Soroya Saira , Mahmood Khalid 
Published: March 2020

Purpose
The purpose of this study is to examine the attitude of faculty members towards knowledge-sharing in the University of Education, Lahore. The impact of personal and organizational factors that may contribute to effective knowledge-sharing among the university’s teaching staff is also analyzed. The factors affecting the willingness of the faculty members to share knowledge are broadly classified as “organizational” and “personal” factors.

Design/methodology/approach
A questionnaire-based survey was conducted on permanent teaching staff working at different campuses of the University of Education all over the province of Punjab, Pakistan. The survey instrument for this study was adapted from four studies. The questionnaires were distributed among 246 faculty members personally.

Findings
The findings of the study showed that the faculty members were familiar with the importance of knowledge-sharing and were also interested in sharing their knowledge and expertise with others. The results showed that organizational factors (trust, reward system and organizational culture) played a vital role in enhancing the knowledge-sharing attitude of faculty members. The impact of these factors on knowledge-sharing attitude was significant.

Originality/value
This is the very first study which explored the personal and organizational factors of knowledge-sharing in a specific academic institution from Pakistan. The findings of the research provided useful insights to the management of the University of Education particularly and other universities in general to design strategies for enhancing knowledge-sharing culture in the higher education institution. These findings may also be helpful for other developing countries.
Enriching the library subject headings with folksonomy
Authors: Yu Wei , Chen Junpeng 
Published: March 2020

Purpose
The purpose of this paper is to explore the potential of enriching the library subject headings with folksonomy for enhancing the visibility and usability of the library subject headings.

Design/methodology/approach
The WorldCat-million data set and SocialBM0311 are preprocessing and over 210,000 library catalog records and 124,482 non-repeating tags were adopted to construct the matrix to observe the semantic relation between library subject headings and folksonomy. The proposed system is compared with the state-of-the-art methods and the parameters are fixed to obtain effective performance.

Findings
The results demonstrate that by integrating different semantic relations from library subject headings and folksonomy, the system’s performance can be improved compared to the benchmark methods. The evaluation results also show that the folksonomy can enrich library subject headings through the semantic relationship.

Originality/value
The proposed method simultaneous weighted matrix factorization can integrate the semantic relation from the library subject headings and folksonomy into one semantic space. The observation of the semantic relation between library subject headings and social tags from folksonomy can help enriching the library subject headings and improving the visibility of the library subject headings.