bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atg39 links and deforms the outer and inner nuclear membranes in selective autophagy of the nucleus
Authors: Mochida Keisuke , Otani Toshifumi , Katsumata Yuto , Kirisako Hiromi , Kakuta Chika , Kotani Tetsuya , Nakatogawa Hitoshi 
Published: March 2021

AbstractIn selective autophagy of the nucleus (hereafter nucleophagy), nucleus-derived double membrane vesicles (NDVs) are formed, sequestered within autophagosomes, and delivered to lysosomes or vacuoles for degradation. In Saccharomyces cerevisiae, the nuclear envelope (NE) protein Atg39 acts as a nucleophagy receptor, which interacts with Atg8 to target NDVs to forming autophagosomal membranes. In this study, we revealed that Atg39 is anchored to the outer nuclear membrane (ONM) via its transmembrane domain and also associated with the inner nuclear membrane (INM) via membrane-binding amphipathic helices (APHs) in its perinuclear space region, thereby linking these membranes. We also revealed that overaccumulation of Atg39 causes the NE to protrude towards the cytoplasm, and the tips of the protrusions are pinched off to generate NDVs. The APHs of Atg39 are crucial for Atg39 assembly in the NE and subsequent NE protrusion. These findings suggest that the nucleophagy receptor Atg39 plays pivotal roles in NE deformation during the generation of NDVs to be degraded by nucleophagy.
Non-parallel morphological divergence following colonization of a new host plant
Authors: Nilsson Kalle J. , Ortega Jesús , Friberg Magne , Runemark Anna 
Published: March 2021

AbstractDivergent ecological selection may diversify conspecific populations evolving into different niches, and may lead to speciation if gene flow is ceased, e.g, due to reinforcement leading to character displacement. Adaptation to the same niche is expected to be parallel. Whether selection against maladaptive hybridization in secondary sympatry also results in parallel divergence in traits that are not directly related to the ecological niches remains an empirical challenge, although such character displacement can be decisive for if ecotypes develop into new species. Here, we use a host shift in the phytophagous peacock flyTephritis conura, with both host races represented in two geographically separate areas East and West of the Baltic Sea to investigate convergence in morphological adaptations. We asked i) if there are consistent morphological adaptations to a host plant shift and ii) if the response to secondary sympatry with the alternate host race is parallel across contact zones. We found surprisingly low and variable, albeit significant, divergence between host races. Only one trait, the length of the female ovipositor, which serves an important function in the interaction with the hosts, was consistently different. Instead, co-existence with the other host race significantly affected the degree of morphological divergence, but the divergence was largely driven by different traits in different contact zones. Thus, local stochastic fixation or reinforcement could generate trait divergence, and additional evidence is needed to conclude whether divergence is locally adaptive.
TheC. elegansPTCHD homolog PTR-4 is required for proper organization of the pre-cuticular apical extracellular matrix
Authors: Cohen Jennifer D. , del Castillo Carla E. Cadena , Kaech Andres , Spang Anne , Sundaram Meera 
Published: March 2021

AbstractThe Patched-related (PTR) superfamily of transmembrane proteins can transport lipids or other hydrophobic molecules across cell membranes. While the hedgehog receptor Patched has been intensively studied, much less is known about the biological roles of other PTR or Patched domain (PTCHD) family members.C. eleganshas a large number of PTR/PTCHD proteins, despite lacking a canonical hedgehog pathway. Here, we show that PTR-4 promotes the assembly of the pre-cuticle apical extracellular matrix (aECM), a transient and molecularly distinct aECM that precedes and patterns the later collagenous cuticle or exoskeleton.ptr-4mutants share many phenotypes with pre-cuticle mutants, including defects in eggshell dissolution, tube shaping, alae (cuticle ridge) structure, and cuticle barrier function. PTR-4 localizes to the apical side of a subset of outward-facing epithelia, in a cyclical manner that peaks when pre-cuticle matrix is present. Finally, PTR-4 acts in a cell non-autonomous manner to properly localize the secreted ZP domain protein LET-653 to the pre-cuticle aECM. We propose that PTR-4 exports lipids or other hydrophobic components of the pre-cuticle aECM.
In vitroteratogenicity testing using a 3D, embryo-like gastruloid system
Authors: Mantziou Veronika , Baillie-Benson Peter , Jaklin Manuela , Kustermann Stefan , Arias Alfonso Martinez , Moris Naomi 
Published: March 2021

AbstractPharmaceuticals that are intended for use in patients of childbearing potential need to be tested for teratogenicity before marketing. Several pharmaceutical companies use animal-freein vitromodels which allow a more rapid selection of lead compounds and contribute to 3Rs principles (‘replace, reduce and refine’) by streamlining the selection of promising compounds that are submitted to further regulatory studies in animals. Currently availablein vitromodels typically rely on adherent monolayer cultures or disorganized 3D structures, both of which lack the spatiotemporal and morphological context of the developing embryo. A newly developed 3D ‘gastruloid’ model has the potential to achieve a more reliable prediction of teratogenicity by providing a robust recapitulation of gastrulation-like events alongside morphological coordination at relatively high-throughput. In this first proof-of-concept study, we used both mouse and human gastruloids to examine a panel of seven reference compounds, with associatedin vivodata and known teratogenic risk, to quantitatively assessin vitroteratogenicity. We observed several gross morphological effects, including significantly reduced elongation or decreased size of the gastruloids, upon exposure to several of the reference compounds. We also observed aberrant gene expression using fluorescent reporters, includingSOX2, BRA, andSOX17, suggestive of multi-lineage differentiation defects and disrupted axial patterning. Finally, we saw that gastruloids recapitulated some of the knownin vivospecies-specific susceptibilities between their mouse and human counterparts. We therefore suggest that gastruloids represent a powerful tool for teratogenicity assessment by enabling relevant physiological recapitulation of early embryonic development, demonstrating their use as a novelin vitroteratogenic model system.
Crystal structures of β-1,4-N-acetylglucosaminyltransferase 2: structural basis for inherited muscular dystrophies
Authors: Yang Jeong Yeh , Halmo Stephanie M. , Praissman Jeremy , Chapla Digantkumar , Singh Danish , Wells Lance , Moremen Kelley W. , Lanzilotta William N. 
Published: March 2021

The canonical O-mannosylation pathway in humans is essential for the functional glycosylation of α-dystroglycan. Disruption of this post-translational modification pathway leads to congenital muscular dystrophies. The first committed step in the construction of a functional matriglycan structure involves the post-translational modification of α-dystroglycan. This is essential for binding extracellular matrix proteins and arenaviruses, and is catalyzed by β-1,4-N-acetylglucosaminyltransferase 2 (POMGNT2). While another glycosyl transferase, β-1,4-N-acetylglucosaminyltransferase 1 (POMGNT1), has been shown to be promiscuous in extending O-mannosylated sites, POMGNT2 has been shown to display significant primary amino-acid selectivity near the site of O-mannosylation. Moreover, several single point mutations in POMGNT2 have been identified in patients with assorted dystroglycanopathies such as Walker–Warburg syndrome and limb girdle muscular dystrophy. To gain insight into POMGNT2 function in humans, the enzyme was expressed as a soluble, secreted fusion protein by transient infection of HEK293 suspension cultures. Here, crystal structures of POMGNT2 (amino-acid residues 25–580) with and without UDP bound are reported. Consistent with a novel fold and a unique domain organization, no molecular-replacement model was available and phases were obtained through crystallization of a selenomethionine variant of the enzyme in the same space group. Tetragonal (space group P4212; unit-cell parameters a = b = 129.8, c = 81.6 Å, α = γ = β = 90°) crystals with UDP bound diffracted to 1.98 Å resolution and contained a single monomer in the asymmetric unit. Orthorhombic (space group P212121; unit-cell parameters a = 142.3, b = 153.9, c = 187.4 Å, α = γ = β = 90°) crystals were also obtained; they diffracted to 2.57 Å resolution and contained four monomers with differential glycosylation patterns and conformations. These structures provide the first rational basis for an explanation of the loss-of-function mutations and offer significant insights into the mechanics of this important human enzyme.
Using VIKOR with structural equation modeling for constructing benchmarks in the Internet industry
Authors: Torlak Nuri Gökhan , Demir Ahmet , Budur Taylan 
Published: March 2021

PurposeThe study uses VIseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR)-structural equation modeling (SEM) to construct benchmarks for service providers and evaluate a multimethodology practice in the Internet industry.Design/methodology/approachThe data were collected using a survey based on an email/interview with 444 Internet users participating. SEM obtained coefficient values by way of customer expectations for Internet service providers. The authors normalized coefficients and integrated them into the VIKOR method for ranking competitors in the Internet industry.FindingsVIKOR-SEM revealed that network and information quality and security/privacy significantly positively impact customer trust while network and information quality and customer trust significantly positively affect Internet users' value perceptions. Customer services do not affect customer trust, while security/privacy and customer services have no significant influence on customer value perceptions. Though customer services and Internet users' trust and value perceptions directly, significantly and positively affect their commitments, the quality of network and information and security/privacy indirectly, significantly and positively influence customer commitments.Research limitations/implicationsThe study was in the Internet industry of Iraq. The results cannot be accurate for the other countries and the service sectors. The researchers/managers can adopt the model in other service sectors to test the multimethodology.Originality/valueVIKOR-SEM evaluated the changes in customer expectations and service providers in the Internet industry.
An intelligent simulation-based framework for automated planning of concrete construction works
Authors: Mohammadi Sina , Tavakolan Mehdi , Zahraie Banafsheh 
Published: March 2021

PurposeThis paper proposes an innovative intelligent simulation-based construction planning framework that introduces a new approach to simulation-based construction planning.Design/methodology/approachIn this approach, the authors developed an ontological inference engine as an integrated part of a constraint-based simulation system that configures the construction processes, defines activities and manages resources considering a variety of requirements and constraints during the simulation. It allows for the incorporation of the latest project information and a deep level of construction planning knowledge in the planning. The construction planning knowledge is represented by an ontology and several semantic rules. Also, the proposed framework uses the project building information model (BIM) to extract information regarding the construction product and the relations between elements. The extracted information is then converted to an ontological format to be useable by the framework.FindingsThe authors implemented the framework in a case study project and tested its usefulness and capabilities. It successfully generated the construction processes, activities and required resources based on the construction product, available resources and the planning rules. It also allowed for a variety of analyses regarding different construction strategies and resource planning. Moreover, 4D BIM models that provide a very good understanding of the construction plan can be automatically generated using the proposed framework.Originality/valueThe active integration between BIM, discrete-event simulation (DES) and ontological knowledge base and inference engine defines a new class of construction simulation with expandable applications.
Audit quality implications of regulatory change in South Africa
Authors: Ndaba Harina , Harber Michael , Maroun Warren 
Published: March 2021

PurposeThis paper explores how technical constructions of audit practice are influenced by mandatory audit firm rotation (MAFR) regulations. The paper responds to calls for additional research on how external regulation influences audit quality and supplements the predominately quantitative research dealing specifically with firm rotation and its relevance for audit quality.Design/methodology/approachData are collected from South Africa which is the latest jurisdiction to adopt MAFR (from 2017). Detailed interviews with 49 participants comprising 24 audit partners and 25 non-auditors are conducted to explore how MAFR can impact audit quality. For this purpose, audit quality is defined according to a schematic developed interpretively and based on professional auditing standards and the prior research on audit quality.FindingsThere is no guarantee that MAFR will bolster auditors' independence or contribute to a more thorough audit approach. On the contrary, the effort required by incoming audit firms to gain an understanding of new clients coupled with material tendering costs is expected to decrease the profitability of audit engagements with adverse implications for audit quality. A loss of client experience and staff retention challenges may contribute further to a decline in audit quality. There may be some improvements to audit practice when an incumbent firm's work is going to be scrutinised by a new auditor but audit methodologies, including the nature and extent of testing performed, are not expected to change significantly because of MAFR. In this way, the regulation may be a symbolic response to a perceived decline in audit quality and auditor independence rather than part of an effective strategy to encourage more rigorous audit practice for the benefit of the users of financial statements.Originality/valueThe current paper provides one of the first exploratory accountants of how MAFR is expected to impact audit practice and, in turn, audit quality. The research responds to the call for more field-work studies on the mechanics of the audit process by engaging directly with practitioners instead of relying on inferential testing of broad audit quality surrogates. The study also makes an important empirical contribution by providing primary evidence on how external regulation influences audit practice from a seldom studied African perspective.
Determinants of working capital: empirical evidence on manufacturing SMEs
Authors: Sardo Filipe , Serrasqueiro Zélia 
Published: March 2021

PurposeThis study seeks to analyse the determinants of working capital of manufacturing small and medium-sized enterprises (SMEs), particularly the effect of the probability of financial distress on working capital.Design/methodology/approachUsing panel data models, the authors analyse a sample of 3994 manufacturing SMEs for the period 2011–2017.FindingsThe results suggest that SMEs pursue conservative working capital management to avoid the failure to fulfil the commitments with creditors. Also, the positive impact of the probability of financial distress on SME working capital suggests that SMEs exposed to a higher probability of bankruptcy invest more in working capital to avoid the risk of default and financing imbalance.Originality/valueThe novelty of this study is to extend the consequences of aggressive or conservative working capital management by analysing the probability of financial distress on working capital.
E-store brand personality congruence for multichannel apparel retail brands
Authors: Chang Jae Youn , Kwon Wi-Suk 
Published: March 2021

PurposeThis study aims at examining the role of the e-store brand personality congruence/incongruence of a multichannel apparel retailer in the formation of consumers' perceived e-store brand fit and e-store patronage intention, based on the concept of image congruence.Design/methodology/approachAn online survey was conducted with a US national sample of 458 female consumers (20–50 years old) who had shopped for clothing online.FindingsResults revealed that e-store brand personality incongruence in three personality dimensions had a negative impact on consumers' e-store patronage intention directly as well as indirectly by reducing the consumers' global perception of the e-store brand fit. Further, the retailer's relevance to the consumer moderated the relationship between the perceived e-store brand fit and e-store patronage intention in that this relationship was significantly greater among consumers with a high (vs low) perceived self-relevance of the retail brand.Practical implicationsThe findings highlight the importance of symbolically integrated cross-channel brand management for multichannel apparel retailers by clearly identifying their brand personality and carefully crafting it into their e-store interface design and e-store visual merchandising to convey the brand personality.Originality/valueThis study expands the application of image congruence to the cross-channel image congruence phenomenon in multichannel retailing environments by examining the e-store brand image congruence employing both direct and indirect approaches.
Managing funerary systems in the pandemic: lessons learned and an application of a scenario simulation in São Paulo City, Brazil
Authors: de Brito Jr Irineu , Cunha Manoel Henrique Capistrano , Tozi Luiz Antonio , Franzese Luiz Augusto , Frazão Márcia Lorena da Silva , Bressane Adriano 
Published: March 2021

PurposeThis study, a practice forum article, aims to presents the lessons learned and the development of a discrete event simulation model to support the funerary system management of São Paulo City, Brazil, during the COVID-19 pandemic.Design/methodology/approachA discrete event simulation model was developed by the authors as soon as the pandemic affected the city of São Paulo, Brazil. Based on the model, several scenarios with varying minimum, median and peak demands (i.e. the number of deaths) were tested and evaluated. The lessons learned from the scenario analysis and implementation of the decision-making of the city government of São Paulo are discussed in this article.FindingsThe lessons learned about the coordination, inventory management and other operational characteristics in funerary logistics during the pandemic are shared with a model, which quantifies the demand for vehicles, coffins, graves and teams in the cemeteries in different simulated scenarios.Practical implicationsThe São Paulo State Civil Defense used this information during the pandemic to prepare the funerary system of the municipality.Social implicationsThe study presents methods to mitigate the sanitary, environmental and psychosocial problems related to the funerary system.Originality/valueStudies on funerary systems are scarce. This study presents the results that supported the dimensioning of the funerary system during the pandemic and operational lessons about the logistics to support decision-making in future events.
Making a difference: workforce skills and capacity for integrated care
Authors: Akehurst Joy , Stronge Paul , Giles Karen , Ling Jonathon 
Published: March 2021

PurposeThe aim of this action research was to explore, from a workforce and a patient/carer perspective, the skills and the capacity required to deliver integrated care and to inform future workforce development and planning in a new integrated care system in England.Design/methodology/approachSemi-structured interviews and focus groups with primary, community, acute care, social care and voluntary care, frontline and managerial staff and with patients and carers receiving these services were undertaken. Data were explored using framework analysis.FindingsAnalysis revealed three overarching themes: achieving teamwork and integration, managing demands on capacity and capability and delivering holistic and user-centred care. An organisational development (OD) process was developed as part of the action research process to facilitate the large-scale workforce changes taking place.Research limitations/implicationsThis study did not consider workforce development and planning challenges for nursing and care staff in residential, nursing care homes or domiciliary services. This part of the workforce is integral to the care pathways for many patients, and in line with the current emerging national focus on this sector, these groups require further examination. Further, data explore service users' and carers' perspectives on workforce skills. It proved challenging to recruit patient and carer respondents for the research due to the nature of their illnesses.Practical implicationsMany of the required skills already existed within the workforce. The OD process facilitated collaborative learning to enhance skills; however, workforce planning across a whole system has challenges in relation to data gathering and management. Ensuring a focus on workforce development and planning is an important part of integrated care development.Social implicationsThis study has implications for social and voluntary sector organisations in respect of inter-agency working practices, as well as the identification of workforce development needs and potential for informing subsequent cross-sector workforce planning arrangements and communication.Originality/valueThis paper helps to identify the issues and benefits of implementing person-centred, integrated teamworking and the implications for workforce planning and OD approaches.