bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of fungal limonene-3-hydroxylases for biotechnological menthol production
Authors: Schempp Florence M. , Strobel Ingmar , Etschmann Maria M. W. , Bierwirth Elena , Panten Johannes , Schewe Hendrik , Schrader Jens , Buchhaupt Markus 
Published: November 2020

AbstractMore than 30,000 tons of menthol are produced every year as a flavor and fragrance compound or as medical component. So far, only extraction from plant material or chemical synthesis is possible. A sustainable alternative approach for menthol production could be a biotechnological-chemical two-step conversion, starting from (+)-limonene, which is a side product of the citrus processing industry. The first step requires a limonene-3-hydroxylase (L3H) activity that specifically catalyzes hydroxylation of limonene at carbon atom 3. Several protein engineering strategies already attempted to create limonene-3-hydroxylases from bacterial cytochrome P450 monooxygenases (CYPs or P450s), which can be efficiently expressed in bacterial hosts. However, their regiospecificity is rather low, if compared to the highly selective L3H enzymes from the biosynthetic pathway towards menthol in Mentha species. The only naturally occurring limonene-3-hydroxylase activity identified in microorganisms so far, was reported for a strain of the black yeast-like fungus Hormonema sp. in South Africa.We have discovered further fungi that can catalyze the intended reaction and identified potential CYP-encoding genes within the genome sequence of one of the strains. Using heterologous gene expression and biotransformation experiments in yeasts, we were able to identify limonene-3-hydroxylases from Aureobasidium pullulans and Hormonema carpetanum. Further characterization of the A. pullulans enzyme demonstrated its high stereospecificity and regioselectivity, its potential for limonene-based menthol production and its additional ability to convert α-and β-pinene to verbenol and pinocarveol, respectively.Importance(−)-Menthol is an important flavor and fragrance compound and furthermore has medicinal uses. To realize a two-step synthesis starting from renewable (+)-limonene, a regioselective limonene-3-hydroxylase enzyme is necessary. We identified enzymes from two different fungi, which catalyze this hydroxylation reaction and represent an important module for the development of a biotechnological process for (−)-menthol production from renewable (+)-limonene.
Muscle Van Gogh-like 2 shapes the neuromuscular synapse by regulating MuSK signaling activity
Authors: Boëx Myriam , Messéant Julien , Cottin Steve , Halliez Marius , Bauché Stéphanie , Buon Céline , Sans Nathalie , Montcouquiol Mireille , Molgó Jordi , Amar Muriel , Ferry Arnaud , Lemaitre Mégane , Rouche Andrée , Langui Dominique , Baskaran Asha , Fontaine Bertrand , Strochlic Laure 
Published: November 2020

AbstractThe development of the neuromuscular junction (NMJ) requires dynamic trans-synaptic coordination orchestrated by secreted factors, including the morphogens of the Wnt family. Yet, how the signal of these synaptic cues is transduced, and particularly during the regulation of acetylcholine receptor (AChR) accumulation in the postsynaptic membrane remains unclear. We explored the function of Van Gogh-Like protein 2 (Vangl2), a core component of Wnt planar cell polarity signaling. We showed that the conditional genetic ablation of Vangl2 in muscle reproduces the NMJ differentiation defects in mice with constitutive Vangl2 deletion. These alterations persisted into adulthood with NMJs disassembly leading to an impairment of neurotransmission and motor function deficits. Mechanistically, we found that Vangl2 and the muscle-specific kinase MuSK acted in the same genetic pathway and that Vangl2 binds MuSK, thus controlling its signaling activity. Our results identify Vangl2 as a key player of the core complex of molecules shaping neuromuscular synapses and shed light on the molecular mechanisms underlying NMJ assembly.
Host-directed FDA-approved drugs with antiviral activity against SARS-CoV-2 identified by hierarchical in silico/in vitro screening methods
Authors: Ginex Tiziana , Garaigorta Urtzi , Ramírez David , Castro Victoria , Nozal Vanesa , Maestro Ines , García-Cárceles Javier , Campillo Nuria E. , Martinez Ana , Gastaminza Pablo , Gil Carmen 
Published: November 2020

AbstractThe unprecedent situation generated by the COVID-19 global emergency prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients.In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way.To this end a multi-target virtual screening approach focused on host-based targets related to viral entry followed by the experimental evaluation of the antiviral activity of selected compounds has been carried out. As a result, five different potentially repurposable drugs interfering with viral entry, cepharantine, clofazimine, metergoline, imatinib and efloxate, have been identified.
Cellular Synchronisation through Unidirectional and Phase-Gated Signalling
Authors: Roth Gregory , Misailidis Georgios , Tsiairis Charisios D. 
Published: November 2020

AbstractMultiple natural and artificial oscillator systems achieve synchronisation when oscillators are coupled. The coupling mechanism, essentially the communication between oscillators, is often assumed to be continuous and bidirectional. However, the cells of the presomitic mesoderm synchronise their gene expression oscillations through Notch signalling, which is intermittent and directed from a ligand-presenting to a receptor-presenting cell. Motivated by this mode of communication we present a phase-gated and unidirectional coupling mechanism. We identify conditions under which it can successfully bring two or more oscillators to cycle in-phase. In the presomitic mesoderm we observed the oscillatory dynamics of two synchronizing cell populations and record one population halting its pace while the other keeps undisturbed, as would be predicted from our model. For the same system another important prediction, convergence to a specific range of phases upon synchronisation is also confirmed. Thus, the proposed mechanism accurately describes the coordinated oscillations of the presomitic mesoderm cells and provides an alternative framework for deciphering synchronisation.
Forever Young: Structural Stability of Telomeric Guanine-Quadruplexes in Presence of Oxidative DNA Lesions
Authors: Miclot Tom , Corbier Camille , Terenzi Alessio , Hognon Cécilia , Grandemange Stéphanie , Barone Giampaolo , Monari Antonio 
Published: November 2020

AbstractHuman telomeric DNA (h-Telo), in G-quadruplex (G4) conformation, is characterized by a remarkable structural stability that confers it the capacity to resist to oxidative stress producing one or even clustered 8-oxoguanine lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics (MD) simulations, that identifies the crucial role of the stability of G4s to oxidative lesions, related also to their biological role as inhibitors of telomerase, an enzyme overexpressed in most cancers associated to oxidative stress.
Kinome-wide RNAi screen uncovers role of Ballchen in maintenance of gene activation by trithorax group in Drosophila
Authors: Khan Muhammad Haider Farooq , Akhtar Jawad , Umer Zain , Shaheen Najma , Shaukat Ammad , Mithani Aziz , Anwar Saima , Tariq Muhammad 
Published: November 2020

AbstractPolycomb group (PcG) and trithorax group (trxG) proteins are evolutionary conserved factors that contribute to cell fate determination and maintenance of cellular identities during development of multicellular organisms. The PcG behaves as repressors to maintain heritable patterns of gene silencing and trxG act as anti-silencing factors by maintaining activation of cell type specific genes. Genetic and molecular analysis has revealed extensive details about how different PcG and trxG complexes antagonize each other to maintain cell fates, however the cellular signaling components that contribute to maintenance of gene expression by PcG/trxG remain elusive. Here, we report an ex vivo kinome-wide RNAi screen in Drosophila aimed to identify cell signaling genes that facilitate trxG to counteract PcG mediated repression. From the list of trxG candidates, Ballchen (BALL), a histone kinase, known to phosphorylate histone H2A at threonine 119 (H2AT119p), was characterized as a trxG regulator. The ball mutant exhibit strong genetic interaction with Polycomb (Pc) and trithorax (trx) mutants and loss of BALL also affects expressions of trxG target genes in ball mutant embryos. BALL co-localizes with Trithorax on chromatin and depletion of BALL results in increased H2AK118 ubiquitination, a histone mark central to PcG mediated gene silencing. Moreover, analysis of genome-wide binding profile of BALL shows an overlap with 85% known binding sites of TRX across the genome. Both BALL and TRX are highly enriched at actively transcribed genes, which also correlate with presence of H3K4me3 and H3K27ac. We propose that BALL mediated signal positively contributes to the maintenance of gene activation by trxG by counteracting the repressive effect of PcG.
Linking meta-omics to the kinetics of denitrification intermediates reveals pH-dependent causes of N2O emissions and nitrite accumulation in soil
Authors: Frostegård Åsa , Vick Silas HW , Lim Natalie YN , Bakken Lars R , Shapleigh James P 
Published: November 2020

AbstractDenitrifier community phenotypes often result in transient accumulation of denitrification (NO3−→NO2−→NO→N2O→N2) intermediates. Consequently, anoxic spells drive NO-, N2O- and possibly HONO-emissions to the atmosphere, affecting both climate and tropospheric chemistry. Soil pH is a key controller of intermediate levels, and while there is a clear negative correlation between pH and emission of N2O, NO2− concentrations instead increase with pH. These divergent trends are probably a combination of direct effects of pH on the expression/activity of denitrification enzymes, and an indirect effect via altered community composition. This was studied by analyzing metagenomics/transcriptomics and phenomics of two soil denitrifier communities, one of pH 3.8 (Soil3.8) and the other 6.8 (Soil6.8). Soil3.8 had severely delayed N2O reduction despite early transcription of nosZ, encoding N2O reductase, by diverse denitrifiers, and of several nosZ accessory genes. This lends support to a post-transcriptional, pH-dependent mechanism acting on the NosZ apo-protein or on enzymes involved in its maturation. Metagenome/metatranscriptome reads of nosZ were almost exclusively clade I in Soil3.8 while clade II dominated in Soil6.8. Reads of genes and transcripts for NO2−-reductase were dominated by nirK over nirS in both soils, while qPCR-based determinations showed the opposite, demonstrating that standard primer pairs only capture a fraction of the nirK community. The -omics results suggested that low NO2− concentrations in acidic soils, often ascribed to abiotic degradation, are primarily due to enzymatic activity. The NO reductase gene qnor was strongly expressed in Soil3.8, suggesting an important role in controlling NO. Production of HONO, for which some studies claim higher, others lower, emissions from NO2− accumulating soil, was estimated to be ten times higher from Soil3.8 than from Soil6.8. The study extends our understanding of denitrification-driven gas emissions and the diversity of bacteria involved and demonstrates that gene and transcript quantifications cannot always reliably predict community phenotypes.
The intraflagellar transport protein IFT20 recruits ATG16L1 to early endosomes to promote autophagosome formation in T cells
Authors: Finetti Francesca , Cassioli Chiara , Cianfanelli Valentina , Zevolini Fabrizia , Onnis Anna , Gesualdo Monica , Brunetti Jlenia , Cecconi Francesco , Baldari Cosima T. 
Published: November 2020

ABSTRACTLymphocyte homeostasis, activation and differentiation crucially rely on basal autophagy. The fine-tuning of this process depends on autophagy-related (ATG) proteins and their interaction with the trafficking machinery that orchestrates the membrane rearrangements leading to autophagosome biogenesis. The underlying mechanisms are as yet not fully understood. The intraflagellar transport (IFT) system, known for its role in cargo transport along the axonemal microtubules of the primary cilium, has emerged as a regulator of autophagy in ciliated cells. Growing evidence indicates that ciliogenesis proteins participate in cilia-independent processes, including autophagy, in the non-ciliated T cell. Here we investigate the mechanism by which IFT20, an integral component of the IFT system, regulates basal T cell autophagy. We show that IFT20 interacts with the core autophagy protein ATG16L1 through its CC domain, which is also essential for its pro-autophagic activity. We demonstrate that IFT20 is required for the association of ATG16L1 with the Golgi complex and early endosomes, both of which have been identified as membrane sources for phagophore elongation. This involves the ability of IFT20 to interact with proteins that are resident at these subcellular localizations, namely the golgin GMAP210 at the Golgi apparatus and Rab5 at early endosomes. GMAP210 depletion, while leading to a dispersion of ATG16L1 from the Golgi, did not affect basal autophagy. Conversely, IFT20 was found to recruit ATG16L1 to early endosomes tagged for autophagosome formation by the BECLIN 1/VPS34/Rab5 complex, which resulted in the local accumulation of LC3. Hence IFT20 participates in autophagosome biogenesis under basal conditions by regulating the localization of ATG16L1 at early endosomes to promote autophagosome biogenesis. These data identify IFT20 as a new regulator of an early step of basal autophagy in T cells.
The cerebellum is involved in internal and external speech error monitoring
Authors: Runnqvist Elin , Chanoine Valérie , Strijkers Kristof , Patamadilok Chotiga , Bonnard Mireille , Nazarian Bruno , Sein Julien , Anton Jean-Luc , Belin Pascal , Alario F.- Xavier 
Published: November 2020

AbstractAn fMRI study examined how speakers inspect their own speech for errors. In a word production task, we observed enhanced involvement of the right posterior cerebellum for trials that were correct, but on which participants were more likely to make a word-as compared to a non-word error. Furthermore, comparing errors to correctly produced utterances, we observed increased activation of the same cerebellar region, in addition to temporal and medial frontal regions. Within the framework associating the cerebellum to forward modelling of upcoming actions, this indicates that forward models of verbal actions contain information about word representations used for error monitoring even before articulation (internal monitoring). Additional resources relying on speech perception and conflict monitoring are deployed during articulation to detect overt errors (external monitoring). In summary, speech monitoring seems to recruit a network of brain regions serving domain general purposes, even for abstract levels of processing.
Leveraging both individual-level genetic data and GWAS summary statistics increases polygenic prediction
Authors: Albiñana Clara , Grove Jakob , McGrath John J. , Agerbo Esben , Wray Naomi R. , Werge Thomas , Børglum Anders D. , Mortensen Preben Bo , Privé Florian , Vilhjálmsson Bjarni J. 
Published: November 2020

AbstractThe accuracy of polygenic risk scores (PRSs) to predict complex diseases increases with the training sample size. PRSs are generally derived based on summary statistics from large meta-analyses of multiple genome-wide association studies (GWAS). However, it is now common for researchers to have access to large individual-level data as well, such as the UK biobank data. To the best of our knowledge, it has not yet been explored how to best combine both types of data (summary statistics and individual-level data) to optimize polygenic prediction. The most widely used approach to combine data is the meta-analysis of GWAS summary statistics (Meta-GWAS), but we show that it does not always provide the most accurate PRS. Through simulations and using twelve real case-control and quantitative traits from both iPSYCH and UK Biobank along with external GWAS summary statistics, we compare Meta-GWAS with two alternative data-combining approaches, stacked clumping and thresholding (SCT) and Meta-PRS. We find that, when large individual-level data is available, the linear combination of PRSs (Meta-PRS) is both a simple alternative to Meta-GWAS and often more accurate.
The resistance in management accounting practices towards a neoliberal economy
Authors: Nagirikandalage Padmi , Binsardi Ben , Kooli Kaouther , Pham Anh Ngoc 
Published: November 2020

PurposeThe purpose of this study is to investigate the resistance in management accounting practices (MAPs) in a developing economy in the manufacturing and service sectors in Vietnam.Design/methodology/approachData collection was carried out using survey questionnaires in Vietnamese language. The questionnaires were distributed to selected respondents from the manufacturing and service organisations in Vietnam. Textual structuralism was used to analyse different categories of data, i.e. survey questionnaires, photos and qualitative texts obtained from the literature.FindingsThe findings indicate that the usage of MAPs is more prevalent in the manufacturing sector than in the service sector. In addition, various traditional and contemporary MAPs are being used concurrently in Vietnam, which challenges the classical twofold dichotomy between mere socialism and mere neoliberalism.Research limitations/implicationsThe textual and photographic structuralism is used in this study to analyse primary data (geography and society and time) in a static setting. Hence, it does not analyse the research phenomena in a dynamic equilibrium setting to view the development of the research phenomena over time. Further research could expand data collection to include longitudinal and dynamic settings.Practical implicationsMAPs can be implemented in economic systems ranging from command to capitalist systems. Although most countries in the world follow a mixed economic system, specific MAPs could be designed for a transitional economic system such as that of Vietnam. This affects both theorists and practitioners in Vietnam applying sustainable MAPs to boost a country's competitiveness during transition.Originality/valueThis study expands understanding of the conformity of MAPs in relation to economic systems under the Communist Party of Vietnam (CPV) – the ruling party of the Socialist Republic of Vietnam. Understanding the differences in the way these MAPs are utilised constitutes an essential area of the accounting discipline to advance MAPs in Vietnamese enterprises and progress theoretical development of sustainable MAPs.
The mechanical properties and corrosion resistance of selective laser melting 30CrMnSiA steel
Authors: Zhang Haoyue , Chang Luqi , Zhang Hongwei , Li Junyan , Yang Zijiang , Qiao Bingxuan , Zhao Zhenjiang , Dong Chaofang , Zhang Kai 
Published: November 2020

PurposeThe purpose of this paper is to study the mechanical and corrosion behaviors of selective laser melting (SLM) 30CrMnSiA steel.Design/methodology/approachThe microstructure, mechanical behavior and corrosion resistance of SLM 30CrMnSiA steel were studied by electrochemical test and immersion experiment.FindingsThe results showed that the microstructure of SLM 30CrMnSiA steel contained equiaxed fine (25.0 µm) ferrite and lamellar pearlite. The tensile strength of SLM 30CrMnSiA steel under the process parameters is 1,447 MPa and the elongation is 7.5%. As the immersion/salt spray test time increased to 15 days/48 h, corrosion mainly occurred in the local position of the sample and corrosion resistance decreased. When the immersion/salt spray test time increased to 30 days/168 h, the corrosion production covered the surface of the samples and the corrosion resistance increased.Originality/valueThe paper can guide the application andin siturepair for low-alloy steel by additive manufacturing.
Influence of national culture on knowledge management process: literature review and research agenda
Authors: Goswami Anil Kumar , Agrawal Rakesh Kumar , Goswami Meghna 
Published: November 2020

PurposeThe purpose of this study is to explore, understand and investigate the relationship between national culture and knowledge management (KM) process.Design/methodology/approachThis study is based on systematically and objectively capturing the contents of extant research papers published by researchers in this area by using the literature review methodology.FindingsThe study demonstrates significant relationship between national culture and KM process. Further, it also provides directions for future research.Practical implicationsThe study will help top management to understand and appreciate the impact of national culture on KM process in organization, where people from different nations are working together. The management may apply appropriate organizational interventions to manage people of different national cultures in effective manner and effective utilization of knowledge of the organization through KM process. This paper will be considered as a quick reference and resource for anyone interested in this area.Originality/valueThis study is a comprehensive literature review of influence of national culture on KM process. Further, it also sets the research agenda for future researchers.
Outsourcing and reverse supply chain performance: a triple bottom line approach
Authors: Agrawal Saurabh , Singh Rajesh Kumar 
Published: November 2020

PurposeOutsourcing has become a strategic decision for most of the organizations in the present context of globalization and circular economy. The objective of proposed study is to empirically investigate the relationship between the outsourcing benefits and triple bottom line (TBL)-based performance of reverse supply chain (RSC) comprising of economic, environmental and social factors.Design/methodology/approachIn the present study, the partial least square path approach of structural equation modeling has been applied for testing hypotheses. A questionnaire was developed for collecting the information and responses from the experts of electronics industry, India. Measurement models were tested for ensuring the fitness of data for further applying partial least square path approach of SEM.FindingsThe results provide insightful information on outsourcing and RSC performance. It reveals that outsourcing decisions are important and have great influence on the economic, environmental and social performance of RSC.Research limitations/implicationsThe study will provide useful guidance to the organizations for outsourcing decisions. One of the limitations of the study is that it has considered data collected from the Indian electronics industry. Therefore, results may not be generalized.Originality/valueThe third-party service providers have core competencies, and they are the experts of providing RSC services. It is also apparent from the exploration of past research and theoretical background that there are limited number of studies focusing on the impact of outsourcing decisions in RSC performance specifically from the TBL perspective. Hence, the proposed study is an effort to explore the impact of outsourcing RSC activities on the performance of RSC from a sustainability perspective.