bluuebunny/crossref_metadata_2025_split huggingface dataset:
A choline-releasing glycerophosphodiesterase essential for phosphatidylcholine biosynthesis and blood stage development in the malaria parasite
Authors: Ramaprasad Abhinay , Burda Paul-Christian , Calvani Enrica , Sait Aaron , Palma-Duran Susana Alejandra , Withers-Martinez Chrislaine , Hackett Fiona , MacRae James , Collinson Lucy , Gilberger Tim-Wolf , Blackman Michael J 
Published: June 2022

SummaryThe malaria parasite Plasmodium falciparum synthesizes significant amounts of phospholipids to meet the demands of replication within red blood cells. De novo phosphatidylcholine (PC) biosynthesis via the Kennedy pathway is essential, requiring choline that is primarily sourced from host serum lysophosphatidylcholine (lysoPC). LysoPC also acts as an environmental sensor to regulate parasite sexual differentiation. Despite these critical roles for host lysoPC, the enzyme(s) involved in its breakdown to free choline for PC synthesis are unknown. Here we show that a parasite glycerophosphodiesterase (PfGDPD) is indispensable for blood stage parasite proliferation. Exogenous choline rescues growth of PfGDPD-null parasites, directly linking PfGDPD function to choline incorporation. Loss of PfGDPD reduces choline uptake from lysoPC, resulting in depletion of several PC species in the parasite, whilst purified PfGDPD releases choline from glycerophosphocholine in vitro. Our results identify PfGDPD as a choline-releasing glycerophosphodiesterase that mediates a critical step in PC biosynthesis and parasite survival.
Crystal structure and functional peculiarities of a primordial Orange Carotenoid Protein (OCPX)
Authors: Slonimskiy Yury B. , Zupnik Andrey O. , Varfolomeeva Larisa A. , Boyko Konstantin M. , Maksimov Eugene G. , Sluchanko Nikolai N. 
Published: June 2022

AbstractThe two-domain photoactive Orange Carotenoid Protein (OCP) confers photoprotection in cyanobacteria and presumably stems from domain fusion. Yet, the primitive thylakoid-less cyanobacteria Gloeobacter encodes a complete OCP. Its photosynthesis regulation lacks the so-called Fluorescence Recovery Protein (FRP), which in Synechocystis inhibits OCP-mediated phycobilisome fluorescence quenching, and Gloeobacter OCP belongs to the recently defined, heterogeneous clade OCPX (GlOCPX), the least characterized compared to OCP2 and especially OCP1 clades. Here we describe the first crystal structure of OCPX and provide its detailed structural and functional comparison with OCP1 from Synechocystis. Monomeric GlOCPX quenches Synechocystis phycobilisomes but displays drastically accelerated, less temperature-dependent recovery after photoactivation, evades regulation by FRP from other species and reveals numerous structural features reflecting its functional peculiarities. Our detailed description of a primordial OCPX sheds light on the evolution of the OCP-dependent photoprotection mechanism, rationalizing subdivision of the OCPX clade into subclades.
Cdc42 prevents precocious Rho1 activation during cytokinesis in a Pak1-dependent manner
Authors: Onwubiko Udo N. , Koory Emma , Pokharel Sahara , Roberts Hayden , Mitoubsi Ahmad , Das Maitreyi 
Published: June 2022

AbstractCytokinesis consists of a series of coordinated multi-step events that partition a dividing cell. Accurate regulation of cytokinesis is essential for proliferation and genome integrity. In fission yeast, these coordinated events ensure that the actomyosin ring and septum start ingressing only after chromosome segregation. How cytokinetic events are coordinated remains unclear. The GTPase Cdc42 is required for the delivery of certain cell wall-building enzymes while the GTPase Rho1 is required for activation of these enzymes. Here we show that Cdc42 prevents early Rho1 activation during cytokinesis. Using an active Rho-probe, we show that even though the Rho1 activators Rgf1 and Rgf3 localize to the division site in early anaphase, Rho1 is not activated until late anaphase, just before the onset of ring constriction. We find that loss of Cdc42 activation enables precocious Rho1 activation in early anaphase. Furthermore, this inhibition of Rho1 activation is dependent on the downstream Cdc42 effector Pak1 kinase. Disrupting pak1 function results in early Rho1 activation accompanied by precocious septum deposition and ring constriction. We provide functional and genetic evidence which indicates that Pak1 regulates Rho1 activation likely via the regulation of its GEF Rgf1. Our work proposes a mechanism of Rho1 regulation by active Cdc42 to coordinate timely septum formation and cytokinesis fidelity.
Design principles of dose-response alignment in coupled GTPase switches
Authors: Qiao Lingxia , Ghosh Pradipta , Rangamani Padmini 
Published: June 2022

Abstract“Dose-response alignment” (DoRA), where the downstream response of cellular signaling path-ways closely matches the fraction of activated receptor, can improve the fidelity of dose information transmission. It is believed that a key component for DoRA is negative feedback and thus a natural question that arises is whether there exist design principles for signaling motifs within such negative feedback loops, which may enable these motifs to attain near-perfect DoRA. Here, we investigated several model formulations of an experimentally validated circuit that couples two molecular switches—mGTPase (monomeric GTPase) and tGTPase (heterotrimeric GTPases) — with negative feedback loops. We find that, in the absence of feedback, the low and intermediate mGTPase activation levels benefit DoRA in the mass action and Hill-function models, respectively. In other cases, where the mass action model with a high mGTPase activation level or the Hill-function model with a non-intermediate mGTPase activation level, the DoRA can be improved by adding negative feedback loops. Furthermore, we found that DoRA in a longer cascade (i.e., tGTPase) can be obtained using Hill-function kinetics under certain conditions. In summary, we show how ranges of activity of mGTPase, reaction kinetics, the negative feedback, and the cascade length affect DoRA. This work provides a framework for improving the DoRA performance in signaling motifs with negative feedback loops.Significance StatementDose-response alignment helps cells faithfully transmit dose information; how this alignment is achieved in motifs with negative feedback is unclear. Through rigorous studies interrogating a naturally occurring motif comprised of two species of GTPases coupled by negative feedback loops, this work reveals the versatile roles of negative feedback loops and GTPase regulators on DoRA. We find that the negative feedback can enhance DoRA only with specific kinetic forms and with certain ranges of GTPases activation levels. This knowledge advances our understanding of the role of negative feedback on DoRA and sheds light on the importance of dynamic range of signaling processes as an essential determinant of how cells transfer information about stimuli. Findings can help design signaling circuits with better DoRA behavior, and ultimately augment cell signaling studies.
Assessment of endocytic traffic and Ocrl function in the developing zebrafish neuroepithelium
Authors: Williams Daniel M. , Gungordu Lale , Jackson-Crawford Anthony , Lowe Martin 
Published: June 2022

AbstractEndocytosis is a vital process, required during development and for maintenance of tissue homeostasis, that allows cells to internalize a wide range of molecules from their environment as well maintain their plasma membrane composition. The ability to visualise endocytosis in vivo requires suitable assays to monitor the process. Here, we describe imaging-based assays to visualize endocytosis in the neuroepithelium of living zebrafish embryos. These assays rely on injection of fluorescent tracers into the brain ventricles followed by live imaging and can be used to study fluid-phase or receptor-mediated endocytosis, for which we use receptor-associated protein (RAP) as a ligand for LDL receptor-related protein (LRP) receptors expressed at the neuroepithelium. Using dual colour imaging combined with transient or stable expression of endocytic markers, it is possible to track the progression of endocytosed tracers and to monitor trafficking dynamics. Using these assays, we reveal a role for the Lowe syndrome protein Ocrl in endocytic trafficking within the neuroepithelium. We also find that the RAP binding receptor Lrp2 appears to only partially contribute to neuroepithelial RAP endocytosis. Altogether, our results provide a basis to track endocytosis within the neuroepithelium in vivo, and support a role for Ocrl in this process.Summary statementWe describe live imaging assays to analyse endocytosis in the zebrafish neuroepithelium and show involvement of the inositol phosphatase OCRL in this process
Decoding gene regulation in the mouse embryo using single-cell multi-omics
Authors: Argelaguet Ricard , Lohoff Tim , Li Jingyu Gavin , Nakhuda Asif , Drage Deborah , Krueger Felix , Velten Lars , Clark Stephen J. , Reik Wolf 
Published: June 2022

AbstractFollowing gastrulation, the three primary germ layers develop into the major organs in a process known as organogenesis. Single-cell RNA sequencing has enabled the profiling of the gene expression dynamics of these cell fate decisions, yet a comprehensive map of the interplay between transcription factors and cis-regulatory elements is lacking, as are the underlying gene regulatory networks. Here we generate a multi-omics atlas of mouse early organogenesis by simultaneously profiling gene expression and chromatin accessibility from tens of thousands of single cells. We develop a computational method to leverage the multimodal readouts to predict transcription factor binding events in cis-regulatory elements, which we then use to infer gene regulatory networks that underpin lineage commitment events. Finally, we show that these models can be used to generatein silicopredictions of the effect of transcription factor perturbations. We validate this experimentally by showing that Brachyury is essential for the differentiation of neuromesodermal progenitors to somitic mesoderm fate by priming cis-regulatory elements. The data set can be interactively explored athttps://www.bioinformatics.babraham.ac.uk/shiny/shiny_multiome_organogenesis/
Proinsulin dependent interaction between ENPL-1/GRP94 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans
Authors: Podraza-Farhanieh Agnieszka , Raj Dorota , Kao Gautam , Naredi Peter 
Published: June 2022

AbstractMaturation of insulin is crucial for insulin secretion and function. ENPL-1/GRP94/HSP90B1 plays an important role in this process. ASNA-1/TRC40/GET3 and ENPL-1/GRP94 are conserved insulin secretion regulators in Caenorhabditis elegans and mammals and mouse mutants display type 2 diabetes. ENPL-1 and GRP94 bind proinsulin and regulate proinsulin levels in C. elegans and cultured cells. Here we found that ASNA-1 and ENPL-1 co-operated to regulate insulin secretion in worms via a physical interaction that required pro-DAF-28/insulin but occurred independently of the insulin binding site of ENPL-1. ASNA-1 acted in neurons to promote DAF-28/insulin secretion. The interaction occurred in insulin expressing neurons and was sensitive to changes in pro-DAF-28 levels. The chaperone form of ASNA-1 is likely bound to ENPL-1. Loss of asna-1 disrupted Golgi trafficking pathways. ASNA-1 localization was affected in enpl-1 mutants and ENPL-1 overexpression partially bypassed ASNA-1 requirement. Taken together, we find a functional interaction between ENPL-1 and ASNA-1 which is necessary to maintain proper insulin secretion in C. elegans and provides insights about how their loss might produce diabetes in mammals.
Urban semiotics: analysing the contemporary diasporic meaning of Petaling Street, Chinatown
Authors: Ng Veronica , Chan Regine 
Published: June 2022

PurposeIn the face of urbanisation, there has been prior and current discourse on the gradual thinning out of street identities. Particularly, the diasporic identity of streets such as Petaling Street (Chinatown) has received increasing attention due to diverse development and gentrification plans for the purpose of tourism and urban development. Current and future urban development plans of Kuala Lumpur have led to the need to analyse Petaling Street's identity. Taking this as a point for departure, this paper aims to analyse the contemporary diasporic identity of Petaling street in the face of rapid urbanisation. While there have been studies that addressed Petaling Street's identity, the focus has been from social, cultural and perceptual perspectives which relates to the intangible aspect of place. Taking an alternative stance, this paper studies the contemporary meaning of Petaling Street through the visual communication of facades.Design/methodology/approachAdapting from Odgen–Richard and Parsaee, semiotics, or the study of signs and symbols, is applied as both theoretical and methodological concept to draw meanings. It examines the visual communication of the cultural products that have evolved from the social processes in shaping the street character. Particularly, this paper examines the street identities by studying the contestation of urban sign and symbols of selected street facades.FindingsThe findings reinforced the contestation of identities in Petaling street, with key signifiers of signages, ornament and colour being physical aspects that contest a sense of Chinese-ness. The functional meaning portrayed by the facades due to social, political and economic factors led to the contestations of meaning formed by society that has left the street in a state of irrelevant and unfamiliarity.Practical implicationsIt calls to action for retention of significant urban elements of street facades to prevent further diminution of diasporic meanings which characterise Petaling Street as a whole in the process of urbanisation.Originality/valueIt provides basis to understand the contemporary identity and values of Petaling Street and the shift in meanings that has left the street in a state of irrelevant and unfamiliarity. This can prevent further diminution of diasporic meanings which characterise Petaling Street as a whole in the process of urbanisation.
Influence of governance instruments on supply chain quality: a qualitative investigation in the dairy industry
Authors: Souza Osvaldo de , Machado Marcio C. , Correa Victor Silva , Telles Renato 
Published: June 2022

PurposeThis paper aims to explore the formal (i.e. contracts, standards, processes, and structure) and informal (i.e. social structure, norms, information sharing, and value system and culture) governance instruments used in supply networks and their influence on quality.Design/methodology/approachThis research is qualitative-exploratory in nature, involving semi-structured interviews with 20 managers from three essential layers in the dairy industry's supply chain: companies that supply essential inputs to milk producers; milk producers; and milk cooperatives.FindingsAnalysis of the generated data show that formal governance instruments have a strong and/or weak influence on products' and operations' quality in the dairy industry context; informal instruments have a strong and/or weak influence on quality, as a counterpart to formal instruments; and the integration of verified governance instruments positively influences the quality of products and operations.Practical implicationsThis paper offers several managerial and practical implications. The first is to encourage suppliers of primary inputs and milk producers to invest in the formal structure, primarily in formal contracts with each other. The second implication suggests the relevance of creating different training and qualification courses with members from all organizational levels. Third, there is a need for cooperatives, encompassing all industries, to consider several informal instruments, complementary to contracts and standards currently used for processes.Originality/valueGovernance instruments can lead to desired supply chain outcomes, including those related to quality. Although previous supply chain studies have investigated the relationship between governance instruments and the supply chain, and quality management and the supply chain, studies on governance instruments' influence on supply chain quality are limited.
Benchmarking performance of new venture travel intermediaries: role of firm value and customer perceived value
Authors: Singh Baljeet , Singh Rohit Kumar , Singh Pancy 
Published: June 2022

PurposeLiterature concerning the linkages between entrepreneurial orientation (EO) and firm performance (FP) has been growing in tourism research. However, the linkage's relevance to new venture travel intermediaries remains vague. This study proposes a model that helps researchers and practitioners understand how EO translates into new venture FP through two strategic perspectives of value creation, i.e. firm value (FV) and customer perceived value (CPV).Design/methodology/approachThe study tests this framework using structural equation modeling on a matched dyadic sample of 127 new venture firms belonging to the Indian travel industry.FindingsThe results posit that FV and CPV partially mediate the relationship between EO and new venture FP. The study advances the existing knowledge on the link between EO and FP and provides insights into how EO can enhance FV and CPV which ultimately enhances FP.Originality/valueThis work is the first to extend and integrate the idea of FV and CPV to entrepreneurship and new venture performance literature. By considering the two strategic aspects of value creation, i.e. FV and CPV, the paper presents a holistic view of value creation through EO.
Lattice Boltzmann study of fluid flow and heat transfer characteristics of a heated porous elliptic cylinder: a two-domain scheme
Authors: Kohanpour Mohammad Sedigh , Imani Gholamreza 
Published: June 2022

Purpose
This study aims to investigate lattice Boltzmann (LB) simulation of the fluid flow and heat transfer characteristics of a heated porous elliptic cylinder in uniform flow based on the two-domain scheme. In the present research, the effect of axis ratio (1 ≤ AR ≤ 2), Reynolds number (5 ≤ Re ≤ 40) and Darcy number (10−4 ≤ Da ≤ 10−2) are studied.

Design/methodology/approach
To perform the LB simulation based on the two-domain scheme, the nonequilibrium extrapolation method is modified to model the heat transfer interfacial conditions required at the curved interface.

Findings
The results show that the axis ratio as well as Reynolds and Darcy numbers significantly affect the fluid flow and heat transfer characteristics of the porous elliptic cylinder. It is shown that for AR > 1, the phenomenon of detached recirculating zone occurs at much higher Darcy numbers compared with the case of the porous circular cylinder (AR = 1). The results show that the location of maximum temperature within the cylinder moves downstream when the Reynolds number, Darcy number and axis ratio increase. It is also concluded that the average Nusselt number of a porous elliptic cylinder is always lower than that of a porous circular cylinder.

Originality/value
The LB simulation of forced convection from a porous cylinder in uniform flow with a curved interface based on the two-domain scheme has not been studied yet.
Family support and business performance of South African female technology entrepreneurs
Authors: Neneh Brownhilder Ngek , Welsh Dianne H.B. 
Published: June 2022

PurposeFemale entrepreneurs play an increasingly recognised role in countries' overall well-being by contributing to job creation, wealth, family income and innovation. This study identifies combinations of family support that enhance business performance most effectively.Design/methodology/approachThis study employs a fuzzy-set qualitative comparative analysis (fsQCA), drawing on 184 technology business owners to identify the family support configurations most conducive to high business performance.FindingsThe results suggest that high levels of emotional and instrumental support are necessary for female technology entrepreneurs to achieve a high firm performance (FP) level when instrumental support at home (ISH) is lacking. As a comparison, male technology entrepreneurs can still achieve a high level of FP when emotional and instrumental support for the business (ISB) is low.Originality/valueThis research contributes to the body of knowledge on women's entrepreneurship in emerging economies, technology entrepreneurs in South Africa and family and business support systems. The authors add to the emerging literature on the potential downsides of family embeddedness by tying theory to the findings on how family embeddedness-related obligations arise when individuals depend on their family's financial support and how this reliance impedes the formation of entrepreneurial intentions.
Mapping the landscape of Makerspaces in higher education: an inventory of research findings
Authors: Pallaris Georgios , Zaphiris Panayiotis , Parmaxi Antigoni 
Published: June 2022

Purpose
The purpose of this study is to chart the development of Makerspaces in higher education (MIHE), by building a map of existing research work in the field. Based on a corpus of 183 manuscripts, published between January 2014 and April 2021, it sets out to describe the range of topics covered under the umbrella of MIHE and provide a holistic view of the field.

Design/methodology/approach
The approach adopted in this research includes development of the 2014–2021 MIHE corpus; literature overview and initial coding scheme development; refinement of the initial coding scheme with the help of a focus group and construction of the MIHE map version 1.0; refinement of the MIHE map version 1.0 following a systematic approach of content analysis and development of the MIHE map version 2.0; evaluation of the proposed structure and inclusiveness of all categories in the MIHE map version 2.0 using card-sorting technique; and, finally, development of the MIHE map version 3.0.

Findings
The research trends in the categories of the MIHE map are discussed, as well as possible future directions in the field.

Originality/value
This paper provides a holistic view of the field of MIHE guiding both junior MIHE researchers to place themselves in the field, and policymakers and decision-makers who attempt to evaluate the current and future scholar activity in the field. Finally, it caters for more experienced researchers to focus on certain underinvestigated domains.