bluuebunny/crossref_metadata_2025_split huggingface dataset:
(p)ppGpp/GTP and malonyl-CoA modulateStaphylococcus aureusadaptation to FASII antibiotics and provide a basis for synergistic bi-therapy
Authors: Pathania Amit , Anba-Mondoloni Jamila , Gominet Myriam , Halpern David , Dairou Julien , Dupont Laëtitia , Lamberet Gilles , Trieu-Cuot Patrick , Gloux Karine , Gruss Alexandra 
Published: March 2020

AbstractFatty acid biosynthesis (FASII) enzymes are considered valid targets for antimicrobial drug development against the human pathogenStaphylococcus aureus. However, incorporation of host fatty acids confers FASII antibiotic adaptation that compromises prospective treatments.S. aureusadapts to FASII inhibitors by a first non-replicative latency period followed by outgrowth. Here we used transcriptional fusions and direct metabolite measurements to investigate the factors that dictate the duration of latency prior to outgrowth. We show that stringent response induction leads to repression of FASII and phospholipid synthesis genes. (p)ppGpp induction inhibits synthesis of malonyl-CoA, a molecule that derepresses FapR, a key regulator of FASII and phospholipid synthesis. Anti-FASII treatment also triggers transient expression of (p)ppGpp-regulated genes during the anti-FASII latency phase, with concomitant repression of FapR regulon expression. These effects are reversed upon outgrowth. GTP depletion, a known consequence of stringent response, also occurs during FASII latency, and is proposed as the common signal linking these responses. We next show that anti-FASII treatment shifts malonyl-CoA distribution between its interactants FapR and FabD, towards FapR, increasing expression of phospholipid synthesis genesplsXandplsCduring outgrowth. We conclude that components of the stringent response dictate malonyl-CoA availability inS. aureusFASII regulation, and contribute to latency prior to anti-FASII-adapted outgrowth. A combinatory approach, coupling a (p)ppGpp inducer and an anti-FASII, blocksS. aureusoutgrowth, opening perspectives for bi-therapy treatment.ImportanceStaphylococcus aureusis a major human bacterial pathogen for which new inhibitors are urgently needed. Antibiotic development has centered on the fatty acid synthesis (FASII) pathway, which provides the building blocks for bacterial membrane phospholipids. However,S. aureusovercomes FASII inhibition and adapts to anti-FASII by using exogenous fatty acids that are abundant in host environments. This adaptation mechanism comprises a transient latency period, followed by bacterial outgrowth. Here we use metabolite sensors and promoter reporters to show that responses to stringent conditions and to FASII inhibition intersect: both involve GTP and malonyl-CoA. These two signaling molecules contribute to modulating the duration of latency prior toS. aureusadaptation outgrowth. We exploit these novel findings to propose a bi-therapy treatment against staphylococcal infections.
Splicing impact of deep exonic missense variants in CAPN3 explored systematically by minigene functional assay
Authors: Dionnet Eugénie , Defour Aurélia , Da Silva Nathalie , Salvi Alexandra , Lévy Nicolas , Krahn Martin , Bartoli Marc , Puppo Francesca , Gorokhova Svetlana 
Published: March 2020

ABSTRACTImproving the accuracy of variant interpretation during diagnostic sequencing is a major goal for genomic medicine. In order to explore an often overlooked splicing effect of missense variants, we developed the functional assay (“minigene”) for the majority of exons of CAPN3, the gene responsible for Limb Girdle Muscular Dystrophy (LGMD). By systematically screening 21 missense variants distributed along the gene, we found that eight clinically relevant missense variants located at a certain distance from the exon/intron borders (deep exonic missense variants) disrupted normal splicing of CAPN3 exons. Several recent machine learning based computational tools failed to predict splicing impact for the majority of these deep exonic missense variants, highlighting the importance of including variants of this type in the training sets during the future algorithm development. Overall, 24 variants in CAPN3 gene were explored, leading to the change in the ACMG classification of seven of them when results of the “minigene” functional assay were taken into account. Our findings reveal previously unknown splicing impact of several clinically important variants in CAPN3 and draw attention to the existence of deep exonic variants with a disruptive effect on gene splicing that could be overlooked by the current approaches in clinical genetics.
A new approach for quantifying phosphorus requirement in an Amazonian fish using CT-scanning
Authors: Menezes Ludmila L.C. , Santos Janaina G. A. , Guimarães Igo G. , Padua Delma M. C. , Machado Vânia M. V. , Souto Cristielle N. 
Published: March 2020

AbstractPhosphorus (P) is an essential mineral for fish growth, as it plays pivotal roles in skeletal development and energy transfer reactions. However, the dietary requirement of this mineral is variable among fish species and the growth stages. Thus, this study aimed to determine the digestible P (dP) requirement for tambaqui in the initial growth stage (± 17 to 150g) using growth data, mineralization of the whole body, vertebrae and scales, as well as blood chemistry as response parameters. A total of 192 tambaqui juveniles of approximately 17 ± 0.85 g were stocked into a water recirculation system. Fish were assigned to 24 70L-tanks using randomized block design (two floors) with six treatments (1.3, 2.4, 4.8, 6.3, 7.8 and 8.8 g kg−1dP) and four replicates. Fish were fed six semipurified diets with increasing levels of dP for 90 days. The dietary requirement of P was estimated using regression models (P < 0.05). Duncan and SNK multiple range tests were used when regression models were not fitted. No mortality or apparent signs of P deficiency were observed. All performance variables were improved with increasing levels of dP in the diet. Based on weight gain, the P requirement was 6.3g kg−1diet while for increased carcass mineral deposition was 6.6g kg−1diet and for adequate mineralization of vertebrae the requirement was 4.75 g dP kg−1diet. The blood chemistry parameters were greatly affected by the dietary P level, except for serum calcium. Thus, the dietary dP requirement for tambaqui juveniles in the early stage was 6.3 g kg−1diet based on growth and bone mineralization.
The genetic architecture of emerging fungicide resistance in populations of a global wheat pathogen
Authors: Pereira Danilo , McDonald Bruce A. , Croll Daniel 
Published: March 2020

AbstractContaining fungal diseases often depends on the application of fungicidal compounds. Fungicides can rapidly lose effectiveness due to the rise of resistant individuals in populations. However, the lack of knowledge about resistance mutations beyond known target genes challenges investigations into pathways to resistance. We used whole-genome sequencing data and association mapping to reveal the multilocus genetic architecture of fungicide resistance in a global panel of 159 isolates ofParastagonospora nodorum, an important fungal pathogen of wheat. We found significant differences in azole resistance among global field populations. The populations evolved distinctive combinations of resistance alleles which can interact synergistically. We identified 34 significantly associated SNPs located in close proximity to genes associated with fungicide resistance in other fungi, including an MFS transporter. Using fungal colony growth rates and melanin production at different temperatures as fitness proxies, we found no evidence that resistance was constrained by genetic trade-offs. Our study demonstrates how genome-wide association studies of a global collection of pathogen strains can recapitulate the emergence of fungicide resistance. The distinct complement of resistance mutations found among populations illustrates how the evolutionary trajectory of fungicide adaptation can be complex and challenging to predict.
Membrane lipid requirements of the lysine transporter Lyp1 fromSaccharomyces cerevisiae
Authors: van‘t Klooster Joury S , Cheng Tan-Yun , Sikkema Hendrik R , Jeucken Aike , Moody D. Branch , Poolman Bert 
Published: March 2020

AbstractMembrane lipids act as solvents and functional cofactors for integral membrane proteins. The yeast plasma membrane is unusual in that it may have a high lipid order, which coincides with low passive permeability for small molecules and a slow lateral diffusion of proteins. Yet, membrane proteins whose functions require altered conformation must have flexibility within membranes. We have determined the molecular composition of yeast plasma membrane lipids located within a defined diameter of model proteins, including the APC-superfamily lysine transporter Lyp1. We now use the composition of lipids that naturally surround Lyp1 to guide testing of lipids that support the normal functioning of the transporter, when reconstituted in vesicles of defined lipid composition. We find that phosphatidylserine and ergosterol are essential for Lyp1 function, and the transport activity displays a sigmoidal relationship with the concentration of these lipids. Non-bilayer lipids stimulate transport activity, but different types are interchangeable. Remarkably, Lyp1 requires a relatively high fraction of lipids with one or more unsaturated acyl chains. The transport data and predictions of the periprotein lipidome of Lyp1, support a new model in which a narrow band of lipids immediately surrounding the transmembrane stalk of a model protein allows conformational changes in the protein.
Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal Segment
Authors: Lillebostad Peder August Gudmundsen , Raasakka Arne , Hjellbrekke Silje Johannessen , Patil Sudarshan , Røstbø Trude , Hollås Hanne , Sakya Siri Aastedatter , Szigetvari Peter D. , Vedeler Anni , Kursula Petri 
Published: March 2020

AbstractThe functions of the annexin family of proteins involve binding to Ca2+, lipid membranes, other proteins, and RNA, and the annexins share a common folded core structure at the C terminus. Annexin A11 (AnxA11) has a long N-terminal region, which is predicted to be disordered, binds RNA, and forms membraneless organelles involved in neuronal transport. Mutations in AnxA11 have been linked to amyotrophic lateral sclerosis (ALS). We studied the structure and stability of AnxA11 and identified a short stabilising segment in the N-terminal end of the folded core, which links domains I and IV. Crystal structure of the AnxA11 core highlights main-chain hydrogen bonding interactions formed through this bridging segment, which are likely conserved in most annexins. The structure was also used to study the currently known ALS mutations in AnxA11. Three of these mutations correspond to buried Arg residues highly conserved in the annexin family, indicating central roles in annexin folding. The structural data provide starting points for detailed structure-function studies of both full-length AnxA11 and the disease variants being identified in ALS.
Audit committee versus other governance mechanisms and the effect of investment opportunities: evidence from Palestine
Authors: Abdeljawad Islam , Oweidat Ghassan A.I. , Saleh Norman Mohd 
Published: March 2020

Purpose
This paper aims to explore how the presence of an audit committee is associated with other corporate governance mechanisms, i.e. board structure, ownership structure and quality of external audit. The present study evaluated whether the presence of the audit committee complements or substitutes other governance mechanisms in Palestinian companies. Moreover, the effect of investment opportunities on the relationship between the formation of the audit committee and the quality of the auditor was addressed.

Design/methodology/approach
The association between the formation of the audit committee and other governance variables was modelled as a binary logistic model. The sample comprising 44 firms listed on Palestine exchange for the period between 2013 and 2017, amounting to 220 firm-year observations.

Findings
Based on the investigation, the results have indicated that board independence, the distinction between the chairman and chief executive officer function, ownership concentration and audit quality enhance the chance of audit committee formation, implying complementary effect. Contrastingly, board size and board ownership serve as a substitute to audit committee formation. It has also been found that investment opportunities act as an effective moderating factor that strengthens the relationship between audit quality and the formation of the audit committee.

Originality/value
The study provides valuable insight into the interaction between multiple corporate governance mechanisms within the economy of Palestine where the external uncertainty is high and investment opportunities are constrained by the decisions of the occupying authority. The findings may help regulators and policymakers in Palestine alongside those of other countries with similar environmental features to revise and update their corporate governance codes to ensure that the best control can be achieved, subsequently attracting more foreign and domestic investments.
Understanding off-site readiness in Indian construction organisations
Authors: Bendi Deepthi , Rana Muhammad Qasim , Arif Mohammed , Goulding Jack Steven , Kaushik Amit Kant 
Published: March 2020

Purpose
This paper presents a bespoke model for understanding off-site construction (OSC) readiness among Indian construction organisations. This model presents 17 variables for discussion, the results from which help support OSC strategic decision-making.

Design/methodology/approach
Factor analysis was used to investigate the relationship between variables to group them into factors. After identifying 26 different variables, these were reduced to 17 using factor analysis and categorised into four groups. Descriptive statistical analysis and factor analysis using SPSS was used to develop a hierarchy of factors that affect OSC readiness in India. These findings were reinforced by five domain experts to support the results.

Findings
Minimising on-site duration, ensuring cost and time certainty and transportation issues were identified as the three most important factors, whereas lack of guidance and scepticism were among the lowest factors affecting the Indian OSC sector.

Research limitations/implications
This research is specifically focused on OSC within the Indian construction sector. As such, data collection, propagation and analysis should be constrained to the population context regarding inference, generalisability and repeatability.

Practical implications
The proffered OSC readiness model offers OSC practitioners an ability to assess the OSC readiness of construction organisations in India. This includes the evaluation and benchmarking of processes in both strategic and operational phases, including highlighting areas of concern and scope for further development (to achieve optimal advantage of OSC methods).

Originality/value
Originality rests with the use of factor analysis and descriptive statistical analysis to study the influence of different construction-related factors and variables on the OSC sector in India. This impact readiness model is context-specific to the Indian OSC sector – providing a unique insight into the causal factors and dependencies that can affect the adoption and uptake of modern methods of construction in India.
Culture in the design of mHealth UI
Authors: Alsswey Ahmed Housni , Al-Samarraie Hosam , El-Qirem Fuad Ali , Alzahrani Ahmed Ibrahim , Alfarraj Osama 
Published: March 2020

Purpose
Designers of mobile applications have long understood the importance of users’ preferences in making the user experience easier, convenient and therefore valuable. The cultural aspects of groups of users are among the key features of users’ design preferences, because each group’s preferences depend on various features that are culturally compatible. The process of integrating culture into the design of a system has always been an important ingredient for effective and interactive human computer interface. This study aims to investigate the design of a mobile health (mHealth) application user interface (UI) based on Arabic culture. It was argued that integrating certain cultural values of specific groups of users into the design of UI would increase their acceptance of the technology.

Design/methodology/approach
A total of 135 users responded to an online survey about their acceptance of a culturally designed mHealth.

Findings
The findings showed that culturally based language, colours, layout and images had a significant relationship with users’ behavioural intention to use the culturally based mHealth UI.

Research limitations/implications
First, the sample and the data collected of this study were restricted to Arab users and Arab culture; therefore, the results cannot be generalized to other cultures and users. Second, the adapted unified theory of acceptance and use of technology model was used in this study instead of the new version, which may expose new perceptions. Third, the cultural aspects of UI design in this study were limited to the images, colours, language and layout.

Practical implications
It encourages UI designers to implement the relevant cultural aspects while developing mobile applications.

Originality/value
Embedding Arab cultural aspects in designing UI for mobile applications to satisfy Arab users and enhance their acceptance toward using mobile applications, which will reflect positively on their lives.
Tourism demonstration system for large-scale museums based on 3D virtual simulation technology
Authors: Hu Yongcai , Sun Wei , Liu Xigang , Gan Quan , Shi Jie 
Published: March 2020

Purpose
The purpose of this study is to enhance audience experience in museum by using three-dimensional (3D) virtual simulation technology.

Design/methodology/approach
In this study, a large space museum building tourism demonstration system based on 3D virtual simulation technology was proposed. Starting from the concept of virtual reality (VR), the characteristics of VR and the classification of VR systems were introduced, and the research status of VR technology at home and abroad and the application of 3D virtual simulation were discussed. Then the key technologies of 3D modeling, 3D scene optimization and 3D simulation driving of 3D virtual simulation were expounded, and the characteristics and application scope of different technical methods were analyzed. Finally, an example of the Hongzhou Kiln 3D network museum was listed.

Findings
The research results showed that 3D virtual simulation has a wide range of applications in the field of VR. Different elements need to be considered for different types of applications, and different contents need to be integrated to achieve the corresponding interaction modes.

Originality/value
Virtual image; multimedia; large space museum; tourism demonstration system; 3D virtual simulation technology.
An assessment of education and continuing professional development (CPD) of academic libraries workforce in Botswana
Authors: Oladokun Olugbade , Mooko Neo P. , Fidzani Babakisi T. 
Published: March 2020

Purpose
The purpose of this study is to assess the current level of education qualifications of the workforce working in academic libraries in Botswana. The study also aims to determine the current and required level of continuing professional development (CPD) of librarians working in academic libraries in Botswana.

Design/methodology/approach
The study adopted positivist research paradigm and quantitative research design using a structured questionnaire to collect data, where survey questions were developed based on existing, tested and verified NeXus1 and NeXus2 instruments developed in Australia.

Findings
Findings revealed that majority (41 or 35.3%) of the academic workforce in Botswana had first degree professional qualification, while those with diploma qualification were 28 or 24.1%; about a quarter of respondents had obtained master’s degree qualification. Most of the CPD activities undertaken were workshops and other workplace training programmes. While about half of the total respondents had attended conferences, less than half of them had published or presented a paper, and mentoring, that should have been given a pride of place in the libraries, largely suffers near neglect. Some knowledge and skills have been acquired on the job and have beneficial impact in the service rendered.

Originality/value
The study seems to be the first of its type in Botswana as a thorough search of literature did not yield any result in the field. What is more, it combines the librarians in public and private universities, colleges of education and institutes of health sciences. Recommendations generated from the findings are likely to improve the services rendered and interest of the librarians in the profession.
Big data driven multi-tier architecture for electric mobility as a service in smart cities
Authors: Anthony Jnr Bokolo , Abbas Petersen Sobah , Ahlers Dirk , Krogstie John 
Published: March 2020

Purpose
Electric mobility as a service (eMaaS) is suggested as a possible solution to ease transportation and lessen environmental issues by providing a collaborative transport sharing infrastructure that is based on electric vehicles (EVs) such as electric cars, electric bicycles and so on. Accordingly, this study aims to propose a multi-tier architecture to support the collection, processing, analytics and usage of mobility data in providing eMaaS within smart cities. The architecture uses application programming interfaces to enable interoperability between different infrastructures required for eMaaS and allow multiple partners to exchange and share data for making decision regarding electric mobility services.

Design/methodology/approach
Design science methodology based on a case study by interview was used to collect data from an infrastructure company in Norway to verify the applicability of the proposed multi-tier architecture.

Findings
Findings suggest that the architecture offers an approach for collecting, aggregating, processing and provisioning of data originating from sources to improve electric mobility in smart cities. More importantly, findings from this study provide guidance for municipalities and policymakers in improving electric mobility services. Moreover, the author’s findings provide a practical data-driven mobility use case that can be used by transport companies in deploying eMaaS in smart cities.

Research limitations/implications
Data was collected from a single company in Norway, hence, it is required to further verify the architecture with data collected from other companies.

Practical implications
eMaaS operates on heterogeneous data, which are generated from EVs and used by citizens and stakeholders such as city administration, municipality transport providers, charging station providers and so on. Therefore, the proposed architecture enables the sharing and usage of generated data as openly available data to be used in creating value-added services to improve citizen’s quality of life and viability of businesses.

Social implications
This study proposes the deployment of electric mobility to address increased usage of vehicles, which contributes to pollution of the environment that has a serious effect on citizen’s quality of life.

Originality/value
This study proposes a multi-tier architecture that stores, processes, analyze and provides data and related services to improve electric mobility within smart cities. The multi-tier architecture aims to support and increase eMaaS operation of EVs toward improving transportation services for city transport operators and citizens for sustainable transport and mobility system.