bluuebunny/crossref_metadata_2025_split huggingface dataset:
IDENTIFYING PLANT GENES SHAPING MICROBIOTA COMPOSITION IN THE BARLEY RHIZOSPHERE
Authors: Escudero-Martinez Carmen , Coulter Max , Terrazas Rodrigo Alegria , Foito Alexandre , Kapadia Rumana , Pietrangelo Laura , Maver Mauro , Sharma Rajiv , Aprile Alessio , Morris Jenny , Hedley Pete E. , Maurer Andreas , Pillen Klaus , Naclerio Gino , Mimmo Tanja , Barton Geoffrey J. , Waugh Robbie , Abbott James , Bulgarelli Davide 
Published: December 2021

AbstractA prerequisite to exploiting soil microbes for sustainable crop production is the identification of the plant genes shaping microbiota composition in the rhizosphere, the interface between roots and soil. Here we use metagenomics information as an external quantitative phenotype to map the host genetic determinants of the rhizosphere microbiota in wild and domesticated genotypes of barley, the fourth most cultivated cereal globally. We identify a small number of loci with a major effect on the composition of rhizosphere communities. One of those, designated the QRMC-3HS, emerges as a major determinant of microbiota composition. We subject soil-grown sibling lines harbouring contrasting alleles at QRMC-3HS and hosting contrasting microbiotas to comparative root RNA-seq profiling. This allows us to identify three primary candidate genes, including a Nucleotide-Binding-Leucine-Rich-Repeat (NLR) gene in a region of structural variation of the barley genome. Our results provide insights into the footprint of crop improvement on the plant’s capacity of shaping rhizosphere microbes.
Enrichment of non-B-form DNA at D. melanogaster centromeres
Authors: Patchigolla Venkata S. P. , Mellone Barbara G. 
Published: December 2021

AbstractCentromeres are essential chromosomal regions that mediate the accurate inheritance of genetic information during eukaryotic cell division. Despite their conserved function, centromeres do not contain conserved DNA sequences and are instead epigenetically marked by the presence of the centromere-specific histone H3 variant CENP-A (centromeric protein A). The functional contribution of centromeric DNA sequences to centromere identity remains elusive. Previous work found that dyad symmetries with a propensity to adopt non-canonical secondary DNA structures are enriched at the centromeres of several species. These findings lead to the proposal that such non-canonical DNA secondary structures may contribute to centromere specification. Here, we analyze the predicted secondary structures of the recently identified centromere DNA sequences from Drosophila melanogaster. Although dyad symmetries are only enriched on the Y centromere, we find that other types of non-canonical DNA structures, including DNA melting and G-quadruplexes, are common features of all D. melanogaster centromeres. Our work is consistent with previous models suggesting that non-canonical DNA secondary structures may be conserved features of centromeres with possible implications for centromere specification.
Single-molecule imaging reveals distinct effects of ligands on CCR5 dynamics depending on its dimerization status
Authors: Momboisse Fanny , Nardi Giacomo , Colin Philippe , Hery Melany , Cordeiro Nelia , Schwartz Olivier , Sauvonnet Nathalie , Arenzana-Seisdedos Fernando , Lagache Thibault , Lagane Bernard , Olivo-Marin Jean-Christophe , Brelot Anne 
Published: December 2021

AbstractG protein-coupled receptors (GPCR) are present at the cell surface in different conformational and oligomeric states. However, how these states impact GPCRs biological function and therapeutic targeting remains incompletely known. Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor in inflammation and the principal entry co-receptor for Human Immunodeficiency Viruses (HIV-1). We used TIRF microscopy and an original statistical method to track and classify the motion of different receptors subpopulations. We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric states and exhibiting transient Brownian and restricted motions. These forms were stabilized differently by distinct ligands. In particular, agonist stimulation restricted the mobility of CCR5 and led to its clustering, a feature depending on β-arrestin, while inverse agonist stimulation exhibited the opposite effect. These results suggest a link between receptor activation and immobilization. Applied to HIV-1 envelope glycoproteins gp120, our quantitative analysis revealed agonist-like properties of gp120s. Distinct gp120s influenced CCR5 dynamics differently, suggesting that they stabilize different CCR5 conformations. Then, using a dimerization-compromized mutant, we showed that dimerization (i) impacts CCR5 precoupling to G proteins, (ii) is a pre-requisite for the immobilization and clustering of receptors upon activation, and (iii) regulates receptor endocytosis, thereby impacting the fate of activated receptors. This study demonstrates that tracking the dynamic behavior of a GPCR is an efficient way to link GPCR conformations to their functions, therefore improving the development of drugs targeting specific receptor conformations.
Multi-omics analysis demonstrates a critical role for GLP methyltransferase in transcriptional repression during oogenesis
Authors: Demond Hannah , Hanna Courtney W. , Castillo-Fernandez Juan , Santos Fátima , Papachristou Evangelia K. , Segonds-Pichon Anne , Kishore Kamal , D’Santos Clive S. , Kelsey Gavin 
Published: December 2021

AbstractGLP (EHMT1) is a multifunctional protein, best known for its role as an H3K9me1 and H3K9me2 methyltransferase through its reportedly obligatory dimerization with G9A (EHMT2). Here, we investigate the role of GLP in the oocyte in comparison to G9A using oocyte-specific conditional knockout mouse models (G9a cKO, Glp cKO, G9a-Glp cDKO). Loss of GLP in Glp cKO and G9a-Glp cDKO oocytes re-capitulated meiotic defects observed in the G9a cKO; however, there was a significant impairment in oocyte maturation and developmental competence in Glp cKO and G9a-Glp cDKO oocytes beyond that observed in the G9a cKO. Consequently, loss of GLP in oogenesis results upon fertilisation in mid-gestation embryonic lethality. To assess the molecular functions of GLP and G9A, we applied a multi-omics approach, supported by immunofluorescence, to identify changes in epigenomic, transcriptomic and proteomic signatures in cKO oocytes. H3K9me2 was equally depleted in all cKO oocytes, whereas H3K9me1 was decreased only upon loss of GLP. The transcriptome, DNA methylome and proteome were markedly more affected in G9a-Glp cDKO than G9a cKO oocytes, with transcriptional de-repression associated with increased protein abundance and gains in genic DNA methylation in G9a-Glp cDKO oocytes. Together, our findings suggest that GLP contributes to transcriptional repression in the oocyte, independent of G9A, and is critical for oogenesis and oocyte developmental competence.
Inhibition of autophagy as a novel therapy for the treatment of neurofibromatosis type 1 tumors
Authors: Stevens M. , Wang Y. , Bouley S.J. , Mandigo T.R. , Sharma A. , Sengupta S. , Housden A. , Oltean S. , Perrimon N. , Walker J.A. , Housden B.E. 
Published: December 2021

ABSTRACTNeurofibromatosis type 1 (NF1) is a genetic disorder associated with various symptoms including the formation of benign tumors along nerves. Drug treatments are currently limited. The MEK inhibitor selumetinib is used for a subset of cases but is not always effective and can cause side effects. Therefore, there is a clear need to discover new drugs to targetNF1-deficient tumor cells. Using aDrosophilacell model of NF1, we performed synthetic lethal screens to identify novel drug targets. We identified 54 candidates, which were validated with variable dose analysis as a secondary screen. Five candidates could be targeted using existing drugs, with autophagy inhibitors (chloroquine (CQ) and bafilomycin A1) showing the greatest potential for selectively killingNF1-deficientDrosophilacells. When further investigating autophagy-related genes, we found that 14 out of 30 genes tested had a synthetic lethal interaction withNF1. These 14 genes are involved in the regulation of all aspects of the autophagy pathway and can be targeted with additional autophagy drugs, although none were as effective as CQ. The lethal effect of autophagy inhibitors was conserved in a panel of humanNF1-deficient Schwann cell lines, highlighting their translational potential. The effect of CQ was also conserved in aDrosophila NF1 in vivomodel and in a xenograftedNF1-deficient tumor cell line in mice, with CQ treatment resulting in a more significant reduction in tumor growth than selumetinib treatment. Furthermore, combined treatment with CQ and selumetinib resulted in a further reduction inNF1-deficient cell viability. In conclusion,NF1-deficient cells are vulnerable to disruption of the autophagy pathway. This pathway represents a promising therapeutic target forNF1-associated tumors, and CQ was identified as a promising candidate drug for the treatment ofNF1tumors.
Global SLAM-Seq for accurate mRNA decay determination and identification of NMD targets
Authors: Alalam Hanna , Zepeda Jorge , Sunnerhagen Per 
Published: December 2021

ABSTRACTGene expression analysis requires accurate measurements of global RNA degradation rates, earlier problematic with methods disruptive to cell physiology. Recently, metabolic RNA labeling emerged as an efficient and minimally invasive technique applied in mammalian cells. Here, we have adapted SH-Linked Alkylation for the Metabolic Sequencing of RNA (SLAM-Seq) for a global mRNA stability study in yeast using 4-thiouracil pulse-chase labeling. We assign high-confidence half-life estimates for 67.5 % of expressed ORFs, and measure a median half-life of 9.4 min. For mRNAs where half-life estimates exist in the literature, their ranking order was in good agreement with previous data, indicating that SLAM-Seq efficiently classifies stable and unstable transcripts.We then leveraged our yeast protocol to identify targets of the Nonsense-mediated decay (NMD) pathway. There are currently no global reports of half-lives in both wild type and NMD defective yeast cells; instead steady-state RNA level changes are used as a proxy. With SLAM-Seq, we assign 580 transcripts as putative NMD targets, based on their measured half-lives in wild-type and upf3Δ mutants. We find 230 novel targets, and observe a strong agreement with previous reports of NMD targets, 60 % of our candidates being identified in previous studies.This indicates that SLAM-Seq is a simpler and more economic method for global quantification of mRNA half-lives. Our adaptation for yeast yielded global quantitative measures of the NMD effect on transcript half-lives, high correlation with RNA half-lives measured previously with more technically challenging protocols, and identification of novel NMD regulated transcripts that escaped prior detection.
Polarized α-synuclein trafficking and transcytosis across Brain Endothelial Cells via Rab7-decorated carriers
Authors: Alam Parvez , Holst Mikkel R. , Lauritsen Line , Nielsen Janni , Nielsen Simone S. E. , Jensen Poul Henning , Brewer Jonathan R. , Otzen Daniel E. , Nielsen Morten S. 
Published: December 2021

AbstractParkinson’s disease is mainly caused by aggregation of α-synuclein (α-syn) in the brain. Exchange of α-syn between the brain and peripheral tissues could have important pathophysiological and therapeutic implications, but the trafficking mechanism of α-syn across the blood brain barrier (BBB) remains unclear. In this study, we therefore investigated uptake and transport mechanisms of α-syn monomers and oligomers across an in vitro BBB model system. Both α-syn monomers and oligomers were internalized by primary brain endothelial cells, with increased restriction of oligomeric over monomeric transport. To enlighten the trafficking route of monomeric α-syn in brain endothelial cells, we investigated co-localization of α-syn and intracellular markers of vesicular transport. Here, we observed the highest colocalization with clathrin, Rab7 and VPS35, suggesting a clathrin-dependent internalization, preferentially followed by a late endosome retromer-connected trafficking pathway. Furthermore, STED microscopy revealed monomeric α-syn trafficking via Rab7-decorated carriers. Knockdown of Caveolin1, VPS35, and Rab7 using siRNA did not affect monomeric α-syn uptake into endothelial cells. However, it significantly reduced transcytosis of monomeric α-syn in the luminal-abluminal direction, suggesting a polarized regulation of monomeric α-syn vesicular transport. Our findings suggest a direct role for Rab7 in polarized trafficking of monomeric α-syn across BBB endothelium, and the potential of Rab7 directed trafficking to constitute a target pathway for new therapeutic strategies against Parkinson’s disease and related synucleinopathies.Significance StatementIn the submitted manuscript, we describe the use of a state-of-the-art porcine blood-brain barrier model based on primary cells to get information about this important issue. We identify several hitherto undescribed cellular pathways to mediate polarized transport of alpha-synuclein. One of these paths we find regulated by Rab7 and can be inhibited by targeting several intracellular proteins such as VPS35, Caveolin1 and Rab7. New knowledge describing brain endothelial intracellular transport systems are highly warranted for identifying new target to alleviate Parkinson’s disease. We believe that our findings could be the seed to establish new therapeutic strategies against Parkinson’s disease and related synucleinopathies.
A framework for facilities management supply chain performance evaluation: case study of hotel buildings
Authors: Abdeen Fathima Nishara , Sandanayake Yasangika Gayani , Ramachandra Thanuja 
Published: December 2021

Purpose
The performance of the facilities management supply chain (FMSC) in the hotel sector is challenged by the diverse nature of parties involved, their relationships and the flows of services and products. Although performance measurement systems have been endorsed by researchers worldwide as a mechanism to evaluate and improve performance, there seems lack of mechanisms to evaluate the FMSC performance in hotels. Hence, this paper aims to develop a framework that would enable to evaluate FMSC performance in hotels.

Design/methodology/approach
A case study strategy was used, where 3 five-star hotels in Sri Lanka were studied for the purpose. The data was collected through semi-structured interviews conducted with 21 professionals involved in FMSC and through document reviews. A content analysis was performed and the framework was developed. This was validated with 3 subject matter experts in the field.

Findings
The study findings revealed that the FMSC process is different from manufacturing and service supply chain (SC) processes as it comprises both product and service elements and incorporates internal, as well as external customers. The developed FMSC process comprises seven sub-processes as follows: delivery of products, delivery of services, sourcing, make/fulfil, delivery of FM services and products, receipt of FM services and receipt of products by customers. Based on the derived FMSC process and the key activities, 38 key performance indicators were developed and used in the framework to evaluate the performance of FMSC.

Originality/value
The developed performance evaluation framework is expected to facilitate performance measurement of the SC and enhance its performance. Further, it would enhance cooperation among FMSC partners and assist in achieving FMSC excellence.
Stakeholder management strategies employed on building projects procured by private corporate organisations in south-western Nigeria
Authors: Olatunde Nathaniel Ayinde 
Published: December 2021

PurposeAdvocates of structured stakeholder management (SM) processes have emphasized the use of the appropriate strategies as the most important process in SM. Yet, research effort in this regard in developing countries has been inadequate. The purpose of the study was to examine the SM strategies used on building projects procured by private corporate organisations in south-western Nigeria to enhance project performance.Design/methodology/approachThe study used a census survey to select 30 projects managers who indicated (from 106 who responded to a first stage questionnaire) that they have participated in structured SM in the study area between 2008 and 2017. A second-stage questionnaire was designed to elicit information from the respondents. Data analysis was done with the use of frequency, percentile and mean score (MS) and analysis of variance (ANOVA).FindingsStakeholders with high power and high interest were managed with the use of “collaborate/partner” strategy (MS = 3.86), stakeholders with high power and low interest were “kept satisfied” (MS = 4.09), stakeholders with low power and high interest were managed by using “keep them informed regularly” strategy (MS = 4.10) and stakeholders with low power and low interest were managed using “monitor and respond when necessary” strategy (M = 3.94). Further results show that static stakeholders with high power were managed by using the “monitor constantly” strategy (MS = 4.11), stakeholders with high power, high legitimacy and high urgency were managed by adopting the “keep satisfied” strategy (MS = 4.26), to manage non-supportive stakeholders, project managers adopted the “keep satisfied” strategy (MS = 4.18) and supportive stakeholders were managed by using “involved” strategy (MS = 4.02). More results showed that there is no significant difference in the opinion of project managers on SM strategies employed irrespective of procurement method.Practical implicationsThe study provided a guide to project managers on the appropriate SM strategies to use for future projects.Originality/valueThe study was an attempt to appraise the SM strategies in relation to the procurement methods and their relationship with project performance.
Home, work or both? The role of paradox mindset in a remote work environment during the COVID-19 pandemic
Authors: Nadiv Ronit 
Published: December 2021

PurposeWhy did some individuals have relatively little trouble balancing work and home demands during the COVID-19 lockdown, while others felt overwhelmed? Although ample studies have recently been generated regarding COVID-19 employment challenges, this question has not yet received sufficient scholarly attention. This research integrates work–home conflict theories with the paradox-mindset framework, in order to suggest a new theoretical approach for understanding individual differences in addressing work–home conflict.Design/methodology/approachDuring the first two weeks of the COVID-19 epidemic in Israel, the author gathered 117 completed questionnaires from their colleagues in the Israeli higher-education system, who were working remotely and teaching online during the lockdown imposed to control the epidemic. Based on a path-model analysis, the author examined whether their experiences of strain and tension in the work domain might be indirectly and positively associated with workplace outcomes via positive associations between these experiences and paradox mindset, as well as negative associations between paradox mindset and work-to-home conflict (WTH) and home-to-work (HTW) conflict.FindingsThe study findings highlight the beneficial effect of paradox mindset on the experience of work–home conflict and its outcomes. Although working remotely has great potential to increase the strain and tension experienced by employees, applying a paradox mindset reduces the experience of work–home conflict and is positively associated with certain work outcomes.Originality/valueThis research integrates work–home conflict theories with the paradox-mindset framework. The beneficial effects of a paradox mindset on the experience of work–home conflict and its outcomes are highlighted.
How does model type influence consumer and online fashion retailing?
Authors: Liang Xiaobei , Hu Xiaojuan , Meng Hu , Jiang Jiang , Wang Guanhua 
Published: December 2021

PurposeModel's physical attractiveness plays an important role in online shopping. The purpose of this paper is to explore the relationships among model type, consumer's perceived amount of information and consumer's approach behaviour.Design/methodology/approachConstrual level theory and anchoring effect are used to develop hypotheses. The authors conducted an online experiment in China, and 229 females participated in this experiment.FindingsCompared with the professional model, the nonprofessional model triggers consumers' more perceived amount of information and approach behaviour. The latter effect is significantly enhanced in the website retailing context. Moreover, perceived amount of information positively affects approach behaviour.Practical implicationsThe findings can help fashion brands understand the roles of model type and the online retailing context in consumer behaviour. It offers guidance on how to improve its marketing strategy scientifically. It can also provide consumers with suggestions for making objective purchasing decisions.Originality/valueThis study is one of the first to examine the effects of two model types (professional model or nonprofessional model) on consumers' perceived amount of information and approach behaviour within two online retailing contexts (website stores or webcast studio).
Fracture properties of GGBS-dolomite geopolymer concrete
Authors: P. Saranya , Nagarajan Praveen , Shashikala A.P. 
Published: December 2021

Purpose
This study aims to predict the fracture properties of geopolymer concrete, which is necessary for studying failure behaviour of concrete.

Design/methodology/approach
Geopolymers are new alternative binders for cement in which polymerization gives strength to concrete rather than through hydration. Geopolymer concrete was developed from industrial byproducts such as GGBS and dolomite. Present study estimates the fracture energy of GGBS geopolymer concrete using three point bending test (RILEM TC50-FMC) with different percentages of dolomite and compare with cement concrete having same strength.

Findings
The fracture properties such as peak load, critical stress intensity factor, fracture energy and characteristic length are found to be higher for GGBS-dolomite geopolymer concrete, when their proportion becomes 70:30.

Originality/value
To the best of the authors’ knowledge, this is an original experimental work.