bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epitranscriptomic reprogramming is required to prevent stress and damage from acetaminophen
Authors: Evke Sara , Melendez J. Andres , Lin Qishan , Begley Thomas J. 
Published: August 2021

AbstractEpitranscriptomic marks, in the form of enzyme catalyzed RNA modifications, play important gene regulatory roles in response to environmental and physiological conditions. However, little is known with respect to how pharmaceuticals influence the epitranscriptome. Here we define how acetaminophen (APAP) induces epitranscriptomic reprogramming and how the writer Alkylation Repair Homolog 8 (Alkbh8) plays a key gene regulatory role in the response. Alkbh8 modifies tRNA selenocysteine (tRNASec) to translationally regulate the production of glutathione peroxidases (Gpx’s) and other selenoproteins, with Gpx enzymes known to play protective roles during APAP toxicity. We demonstrate that APAP increases toxicity and markers of damage, and decreases selenoprotein levels in Alkbh8 deficient mouse livers, when compared to wildtype. APAP also promotes large scale reprogramming of 31 RNA marks comprising the liver tRNA epitranscriptome including: 5-methoxycarbonylmethyluridine (mcm5U), isopentenyladenosine (i6A), pseudouridine (Ψ), and 1-methyladenosine (m1A) modifications linked to tRNASec and many others. Alkbh8 deficiency also leads to wide-spread epitranscriptomic dysregulation in response to APAP, demonstrating that a single writer defect can promote downstream changes to a large spectrum of RNA modifications. Our study highlights the importance of RNA modifications and translational responses to APAP, identifies writers as key modulators of stress responses in vivo and supports the idea that the epitranscriptome may play important roles in responses to pharmaceuticals.
Enhancer-promoter competition between homologous alleles leads to reduced transcription in early Drosophila embryos
Authors: Deng Hao , Lim Bomyi 
Published: August 2021

AbstractThe mechanism by which transcriptional machinery is recruited to enhancers and promoters to regulate gene expression is one of the most challenging and extensively studied questions in modern biology. Here, we ask if inter-allelic interactions between two homologous alleles can affect gene regulation. Using MS2- and PP7-based, allele-specific live imaging assay, we visualized de novo transcription of a reporter gene in hemizygous and homozygous Drosophila embryos. Surprisingly, each homozygous allele produced fewer RNAs than the hemizygous allele, suggesting the possibility of allelic competition in homozygotes. Moreover, the MS2-yellow reporter gene showed reduced transcriptional activity when a partial transcription unit (enhancer or promoter only) was in the homologous position. We propose that the transcriptional machinery that binds to both the enhancer and promoter region, such as RNA Pol II or preinitiation complexes, may be responsible for the allelic competition. To support this idea, we showed that the homologous alleles did not interfere with each other in earlier nuclear cycles when Pol II is in excess, while the degree of interference gradually increased in nuclear cycle 14. Such allelic competition was observed for endogenous snail as well. Our study provides new insights into the role of 3D inter-allelic interactions in gene regulation.
Tuning levels of low-complexity domain interactions to modulate endogenous oncogenic transcription
Authors: Chong Shasha , Graham Thomas G.W. , Dugast-Darzacq Claire , Dailey Gina M. , Darzacq Xavier , Tjian Robert 
Published: August 2021

AbstractGene activation by mammalian transcription factors (TFs) requires dynamic, multivalent, and selective interactions of their intrinsically disordered low-complexity domains (LCDs), but how such interactions mediate transcription remains unclear. It has been proposed that extensive LCD-LCD interactions culminating in liquid-liquid phase separation (LLPS) of TFs is the dominant mechanism underlying transactivation. Here, we investigated how tuning the amount and localization of LCD-LCD interactions in vivo affects transcription of endogenous human genes. Quantitative single-cell and single-molecule imaging reveals that the oncogenic TF EWS/FLI1 requires a finely tuned range of LCD-LCD interactions to efficiently activate target genes. Modest or more dramatic increases in LCD-LCD interactions toward putative LLPS repress EWS/FLI1-driven transcription in patient cells. Likewise, ectopically creating LCD-LCD interactions to sequester EWS/FLI1 into a bona fide LLPS compartment, the nucleolus, inhibits EWS/FLI1-driven transcription and oncogenic transformation. Our findings reveal fundamental principles underlying LCD-mediated transcription and suggest mislocalizing specific LCD-LCD interactions as a novel therapeutic strategy for targeting disease-causing TFs.
Stimulation of the Dorsal Root Ganglion using an Injectrode®
Authors: Dalrymple Ashley N , Ting Jordyn E , Bose Rohit , Trevathan James K , Nieuwoudt Stephan , Lempka Scott F , Franke Manfred , Ludwig Kip A , Shoffstall Andrew J , Fisher Lee E , Weber Douglas J 
Published: August 2021

ABSTRACTObjectiveThe goal of this work was to compare afferent fiber recruitment by dorsal root ganglion (DRG) stimulation using an injectable polymer electrode (Injectrode®) and a more traditional cylindrical metal electrode.ApproachWe exposed the L6 and L7 DRG in four cats via a partial laminectomy or burr hole. We stimulated the DRG using an Injectrode or a stainless steel electrode using biphasic pulses at three different pulse widths (80, 150, 300 μs) and pulse amplitudes spanning the range used for clinical DRG stimulation. We recorded antidromic evoked compound action potentials (ECAPs) in the sciatic, tibial, and common peroneal nerves using nerve cuffs. We calculated the conduction velocity of the ECAPs and determined the charge-thresholds and recruitment rates for ECAPs from Aα, Aβ, and Aδ fibers. We also performed electrochemical impedance spectroscopy measurements for both electrode types.Main ResultsThe ECAP thresholds for the Injectrode did not differ from the stainless steel electrode across all primary afferents (Aα, Aβ, Aδ) and pulse widths; charge-thresholds increased with wider pulse widths. Thresholds for generating ECAPs from Aβ fibers were 100.0 ± 32.3 nC using the stainless steel electrode, and 90.9 ± 42.9 nC using the Injectrode. The ECAP thresholds from the Injectrode were consistent over several hours of stimulation. The rate of recruitment was similar between the Injectrodes and stainless steel electrode and decreased with wider pulse widths.SignificanceThe Injectrode can effectively excite primary afferents when used for DRG stimulation within the range of parameters used for clinical DRG stimulation. The Injectrode can be implanted through minimally invasive techniques while achieving similar neural activation to conventional electrodes, making it an excellent candidate for future DRG stimulation and neuroprosthetic applications.
Metagenomic Discovery of CRISPR-Associated Transposons
Authors: Rybarski James R. , Hu Kuang , Hill Alexis M. , Wilke Claus O. , Finkelstein Ilya J. 
Published: August 2021

AbstractCRISPR-associated transposons (CASTs) co-opt Cas genes for RNA-guided transposition. CASTs are exceedingly rare in genomic databases; recent surveys have reported Tn7-like transposons that co-opt Type I-F, I-B, and V-K CRISPR effectors. Here, we expand the diversity of reported CAST systems via a bioinformatic search of metagenomic databases. We discover new architectures for all known CASTs, including novel arrangements of the Cascade effectors, new self-targeting modalities, and minimal V-K systems. We also describe new families of CASTs that have co-opted the Type I-C and Type IV CRISPR-Cas systems. Our search for non-Tn7 CASTs identifies putative candidates that co-opt Cas12a for horizontal gene transfer. These new systems shed light on how CRISPR systems have co-evolved with transposases and expand the programmable gene editing toolkit.
Batch experiments demonstrating a two-stage bacterial process coupling methanotrophic and heterotrophic bacteria for 1-alkene production from methane
Authors: Khanongnuch Ramita , Mangayil Rahul , Santala Ville , Hestnes Anne Grethe , Svenning Mette Marianne , Rissanen Antti J 
Published: August 2021

AbstractMethane (CH4) is a sustainable carbon feedstock source for aerobic CH4-oxidizing bacteria (methanotrophs) to produce value-added chemicals. Under substrate-limited (e.g., CH4, oxygen and nitrogen) conditions, CH4 oxidation results in the production of various short-chain organic acids and platform chemicals. These CH4-derived products could be broadened by utilizing them as a feedstock for heterotrophic bacteria. As a proof of concept, a two-stage system for CH4 abatement and 1-alkene production was developed in this study. Types I and II methanotrophs, i.e., Methylobacter tundripaludum SV96 and Methylocystis rosea SV97, respectively, were investigated in batch tests under different CH4 and air supplementation schemes. CH4 oxidation under either microaerobic or aerobic conditions induced the production of formate, acetate, succinate, and malate in M. tundripaludum SV96, accounting for 4.8-7.0% of consumed CH4-carbon while M. rosea SV97 produced the same compounds except for malate, and with lower efficiency than M. tundripaludum SV96, accounting for 0.7-1.8% of consumed CH4-carbon For the first time, the organic acids-rich spent media of methanotrophs were successfully used for 1-alkene production using engineered Acinetobacter baylyi ADP1 ‘tesA-undA cells. The highest yield of 1-undecene was obtained from spent medium of M. tundripaludum SV96 at 68.9 ± 11.6 μmol mol Csubstrate−1.
CNN based Heuristic Function for A* Pathfinding Algorithm: Using Spatial Vector Data to Reconstruct Smooth and Natural Looking Plant Roots
Authors: Yasrab Robail , Pound Michael P 
Published: August 2021

AbstractIn this work we propose an extension to recent methods for the reconstruction of root architectures in 2-dimensions. Recent methods for the automatic root analysis have proposed deep learned segmentation of root images followed by path finding such as Dijkstra’s algorithm to reconstruct root topology. These approaches assume that roots are separate, and that a shortest path within the image foreground represents a reliable reconstruction of the underlying root structure. This approach is prone to error where roots grow in close proximity, with path finding algorithms prone to taking “short cuts” and overlapping much of the root material. Here we extend these methods to also consider root angle, allowing a more informed shortest path search that disambiguates roots growing close together. We adapt a CNN architecture to also predict the angle of root material at each foreground position, and utilise this additional information within shortest path searchers to improve root reconstruction. Our results show an improved ability to separate clustered roots.
Complexity of brain dynamics as a correlate of consciousness in anaesthetized monkeys
Authors: Fuentes Nicolas , García Alexis , Guevara Ramón , Orofino Roberto , Mateos Diego M. 
Published: August 2021

AbstractThe use of anaesthesia is a fundamental tool in the investigation of consciousness. Anesthesia procedures allow to investigate different states of consciousness from sedation to deep anesthesia within controlled scenarios. In this study we use information quantifiers to measure the complexity of electrocorticogram recordings in monkeys. We apply these metrics to compare different stages of general anesthesia for evaluating consciousness in several anesthesia protocols. We find that the complexity of brain activity can be used as a correlate of consciousness. For two of the anaesthetics used, propofol and medetomidine, we find that the anaesthetised state is accompanied by a reduction in the complexity of brain activity. On the other hand we observe that use of ketamine produces an increase in complexity measurements. We relate this observation with increase activity within certain brain regions associated with the ketamine used doses. Our measurements indicate that complexity of brain activity is a good indicator for a general evaluation of different levels of consciousness awareness, both in anesthetized and non anesthetizes states.
Treatment of a metabolic liver disease by in vivo prime editing in mice
Authors: Böck Desirée , Rothgangl Tanja , Villiger Lukas , Schmidheini Lukas , Mathis Nicholas , Ioannidi Eleonora , Kreutzer Susanne , Kontarakis Zacharias , Rimann Nicole , Grisch-Chan Hiu Man , Thöny Beat , Schwank Gerald 
Published: August 2021

AbstractPrime editing is a highly versatile CRISPR-based genome editing technology with the potential to correct the vast majority of pathogenic mutations (1). However, correction of a disease phenotype in vivo in somatic tissues has not been demonstrated thus far. Here, we establish proof-of-concept for in vivo prime editing and repair the metabolic liver disease phenylketonuria (PKU) in mice. We first developed a size-reduced SpCas9 prime editor (PE) lacking the RNaseH domain of the reverse transcriptase (PE2ΔRnH), and a linker- and NLS-optimized intein-split PE construct (PE2 p.1153) for delivery by adeno-associated virus (AAV) vectors. Systemic dual AAV-mediated delivery of this variant into the liver of neonatal mice enabled installation of a transversion mutation at the Dnmt1 locus with an average efficiency of 15%, and delivery of unsplit PE2ΔRnH using human adenoviral vector 5 (AdV5) further increased editing rates to 58%. PE2ΔRnH-encoding AdV5 was also used to correct the disease-causing mutation of the phenylalanine hydroxylase (Pah)enu2 allele in phenylketonuria (PKU) mice with an average efficiency of 8% (up to 17.3%), leading to therapeutic reduction of blood phenylalanine (L-Phe) levels. Our study demonstrates in vivo prime editing in the liver with high precision and editing rates sufficient to treat a number of metabolic liver diseases, emphasizing the potential of prime editing for future therapeutic applications.One Sentence SummaryIn vivo prime editing corrects phenylketonuria in mice.
Multi-source information fusion based on factor graph in autonomous underwater vehicles navigation systems
Authors: Ma Xiaoshuang , Liu Xixiang , Li Chen-Long , Che Shuangliang 
Published: August 2021

Purpose
This paper aims to present a multi-source information fusion algorithm based on factor graph for autonomous underwater vehicles (AUVs) navigation and positioning to address the asynchronous and heterogeneous problem of multiple sensors.

Design/methodology/approach
The factor graph is formulated by joint probability distribution function (pdf) random variables. All available measurements are processed into an optimal navigation solution by the message passing algorithm in the factor graph model. To further aid high-rate navigation solutions, the equivalent inertial measurement unit (IMU) factor is introduced to replace several consecutive IMU measurements in the factor graph model.

Findings
The proposed factor graph was demonstrated both in a simulated and vehicle environment using IMU, Doppler Velocity Log, terrain-aided navigation, magnetic compass pilot and depth meter sensors. Simulation results showed that the proposed factor graph processes all available measurements into the considerably improved navigation performance, computational efficiency and complexity compared with the un-simplified factor graph and the federal Kalman filtering methods. Semi-physical experiment results also verified the robustness and effectiveness.

Originality/value
The proposed factor graph scheme supported a plug and play capability to easily fuse asynchronous heterogeneous measurements information in AUV navigation systems.
Understanding corporate culture and business performance from a Confucian perspective
Authors: Tian Vane-Ing , Tang Felix , Tse Alan C.B. 
Published: August 2021

PurposeThis paper aims to develop a culturally sensitive model based on the Chinese Confucian philosophy and normative ethics, which emphasizes the wholehearted social responsibility of a Junzi (a noble man). Analogous to the popular marketing concept and strategic marketing orientation concepts, the authors define the Junzi concept as a business philosophy and Junzi orientation as the implementation of this philosophy. It proposes a Junzi orientation has a positive influence on companies' performances.Design/methodology/approachAn 18-item scale comprising five dimensions: (1) Ren – benevolence, humaneness; (2) Yi – appropriateness, righteousness; (3) Li – propriety, harmonious differentiation; (4) Zhi – wisdom, knowledge management; and (5) Xin – integrity, trustworthiness, was developed to measure Junzi orientation. A total of 423 questionnaires were collected from different industries in Hong Kong, and confirmatory factor analyses were conducted.FindingsThe multidimensional behavioral construct of Junzi orientation scale was reliable and valid. The data supported that Junzi orientation has a positive influence on companies' performances.Practical implicationsThe paper suggests that Junzi orientation could enhance a firm's competitive advantage.Originality/valueThis paper develops a culturally sensitive business orientation scale based on Chinese Confucianism and normative ethics.
Examining the consequences of adaptive selling behavior by door-to-door salespeople in the Korean cosmetic industry
Authors: Amenuvor Fortune Edem , Yi Ho-Taek , Boateng Henry 
Published: August 2021

PurposeThis paper aims to assess the effect of adaptive selling behavior on customer outcomes, mutual outcomes and salesperson outcomes.Design/methodology/approachThe respondents were salespeople and customers in selected door-to-door cosmetics companies in South Korea. A questionnaire was used to collect the data. Structural equation modeling was used to analyze the data in this study.FindingsFindings show that adaptive selling behavior positively affects customer satisfaction, customer loyalty, sales performance, job satisfaction and relationship quality. These findings suggest that adaptive selling is crucial for the firm's survival depending on the industry and the product. Additionally, unlike previous studies, the authors use salespeople's self-reporting responses and customer-reporting of salespeople, which further enhances the richness and uniqueness of the results.Originality/valueStudies investigating mutual outcomes of adaptive selling behavior are scarce. The study also emphasizes that adaptive selling behavior enhances salesperson outcomes and customer outcomes and primarily uses dyadic data between door-to-door salespeople and their customers, which is not very common.
Auditor tenure, investor protection and accounting quality: international evidence
Authors: Kamarudin Khairul Anuar , Wan Ismail Wan Adibah , Ariff Akmalia M. 
Published: August 2021

Purpose
This study aims to investigate whether auditor tenure has a significant influence on accounting quality and whether investor protection moderates the effect of auditor tenure on accounting quality.

Design/methodology/approach
This study uses weighted least squares regression on a sample of 77,855 firm-year observations from 36 countries during the period 2010–2016. This study uses the absolute value of performance-matched discretionary accruals to measure financial reporting quality.

Findings
This study finds that a longer auditor tenure is associated with higher accounting quality, thus supporting the knowledge effect arguments. The results on the joint effect of investor protection and auditor tenure show evidence of the substitutive effect of investor protection, where the positive impact of auditor tenure on accounting quality is weaker in a high investor-protection environment.

Practical implications
These findings provide input for policy implications involving the auditing profession. Regulators may need to weigh the costs and benefits of mandatory audit rotation because country-level institutional factors influence auditing regulations and practices, as well as the auditors’ behaviors.

Originality/value
This study adds to the limited, albeit important, evidence on the joint effect of auditor tenure and country-level governance on accounting quality. The authors respond to the call by Brooks et al. (2017) for more evidence on the role of audits on financial reporting outcomes across various legal institutions for creating effective policies.
Do sustainability practices influence financial performance? Evidence from the Nordic financial industry
Authors: Rahi ABM Fazle , Akter Ruzlin , Johansson Jeaneth 
Published: August 2021

PurposeThe purpose of this study is to explore the impact of sustainability (environmental, social and governance or ESG) practices on the financial performance (FP) of the Nordic financial industry.Design/methodology/approachThe study covers a sample selection of observations for a total of 152 firm-years for 39 financial companies within the Nordic region (Sweden, Denmark, Finland and Norway) for the business years including 2015–2019. Data regarding ESG and FP indicators were extracted from the Thomson Reuters Eikon database in July 2020. This is a quantitative study using regression and a generalized method of moments.FindingsUsing static and dynamic estimators, the authors found both positive and negative impacts of sustainability practice on FP. The authors identified a negative relationship between ESG practices and FP (return on invested capital, return on equity and earnings per share). The authors identified a positive relationship between governance and return on assets.Originality/valueA key contribution to the accounting literature is the finding that there is a risk for financial firms in adopting sustainability practices, as they follow a logic that contradicts the purely economic rationale. On the other hand, the positive relationship between governance and FP helps not only companies but also regulators and researchers to understand the positive impact of a good governance structure.