bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of asymmetric membranes and interleaflet coupling as intermediates in membrane fusion
Authors: Perez Marcos Arribas , Beales Paul A. 
Published: August 2022

AbstractMembrane fusion is a tool to increase the complexity of model membrane systems. Here, we use silica nanoparticles to fuse liquid-disordered DOPC giant GUVs and liquid-ordered DPPC:Cholesterol (7:3) GUVs. After fusion, GUVs display large membrane domains as confirmed by fluorescence confocal microscopy. Laurdan spectral imaging of the membrane phases in the fused GUVs shows differences compared to the initial vesicles indicating some lipid redistribution between phase domains as dictated by the tie lines of the phase diagram. Remarkably, using real-time confocal microscopy we were able to record the dynamics of formation of asymmetric membrane domains in hemifused GUVs and detected interleaflet coupling phenomena by which the DOPC-rich liquid-disordered domains in outer monolayer modulates the phase state of the DPPC:Cholesterol inner membrane leaflet which transitions from liquid-ordered to liquid-disordered phase.. We find that internal membrane stresses generated by membrane asymmetry enhance the efficiency of full fusion compared to our previous studies on symmetric vesicle fusion. Furthermore, under these conditions, the liquid disordered monolayer dictates the bilayer phase state of asymmetric membrane domains in >90% of observed cases. By comparison to the findings of previous literature, we suggest that which monolayer phase dominates the bilayer properties could be a mechanoresponsive signalling mechanism sensitive to the local membrane environment.Statement of SignificanceNatural biomembranes are highly asymmetric in lipid composition between the two leaflets of its bilayer structure. While the majority of membrane biophysics studies are conducted on symmetric lipid bilayers, it has become increasingly apparent that these asymmetric lipid compositions have a strong impact on the overall properties and behaviours of the membrane. However, achieving controlled membrane asymmetry in artificial model membranes is non-trivial, making the study of related biophysical mechanisms challenging. Here, we present an experimental framework to image the dynamics of asymmetric membrane domains formed as intermediates during membrane fusion of giant unilamellar vesicles (GUVs) triggered by silica nanoparticles. We directly observe interleaflet coupling of the phases in asymmetric membranes, where the liquid disordered domains most commonly dominate. By comparison with other literature on asymmetric membranes, this may indicate that the phase state of asymmetric membranes can be mechanoresponsive to its local environment. Furthermore, enhanced efficiency of full fusion of these GUV membranes indicates that stresses generated by membrane asymmetry can promote the formation of the full fusion pore during vesicle fusion processes.
Heterogeneous neuronal activity in the ventral tegmental area coordinates dopamine release in the nucleus accumbens
Authors: Hill Daniel F. , Olson Zachary G. , Bartlett Mitchell J. , Falk Torsten , Heien Michael L. , Cowen Stephen L. 
Published: August 2022

AbstractDopamine release in the ventral striatum is fundamental to adaptive appetitive behavior. Frustratingly, technological, and methodological hurdles have limited the investigation of the mechanisms that drive phasic dopamine release. Although dopamine neuron activation in the ventral tegmental area (VTA) surely results in dopamine release, how populations of these neurons coordinate their activities in time to modulate the temporal pattern of release remains unclear. Additionally, burgeoning evidence suggests that control over striatal dopamine release is not solely regulated by the burst firing of VTA neurons or even cell-body activation of these neurons. Here, we recorded VTA neurons while simultaneously monitoring pharmacologically induced phasic dopamine release events in the ventral striatum (nucleus accumbens core) of anesthetized rats. On average, dopaminergic and non-dopaminergic neurons increased activity at the time of the onset of release and decreased at the time of peak release; however, the tuning of individual VTA neurons to dopamine release was notably heterogenous, with subsets of neurons responding prior to release, at release onset, or during release. Other neurons were notably silent during release but active otherwise. Interestingly, both putative dopaminergic and non-dopaminergic neurons expressed this temporally heterogeneous response pattern. Furthermore, the firing activity of dopaminergic, but not non-dopaminergic neurons, correlated with the magnitude of dopamine release. These data suggest that populations of VTA neurons become active at distinct times of a dopamine release event to sculpt the temporal pattern of release.
Didemnin B and ternatin-4 inhibit conformational changes in eEF1A required for aminoacyl-tRNA accommodation into mammalian ribosomes
Authors: Juette Manuel F. , Carelli Jordan D. , Rundlet Emily J. , Brown Alan , Shao Sichen , Ferguson Angelica , Wasserman Michael R. , Holm Mikael , Taunton Jack , Blanchard Scott C. 
Published: August 2022

AbstractRapid and accurate mRNA translation requires efficient codon-dependent delivery of the correct aminoacyl-tRNA (aa-tRNA) to the ribosomal A site. In mammals, this fidelity-determining reaction is facilitated by the GTPase elongation factor-1 alpha (eEF1A), which escorts aa-tRNA as an eEF1A(GTP)-aa-tRNA ternary complex into the ribosome. Two structurally unrelated cyclic peptides didemnin B and ternatin-4 bind to the eEF1A(GTP)-aa-tRNA ternary complex and inhibit translation. Here, we employ single-molecule fluorescence imaging and cryogenic electron microscopy to determine how these natural products inhibit translational elongation on mammalian ribosomes. By binding to a common allosteric site on eEF1A, didemnin B and ternatin-4 trap eEF1A in its GTPase-activated conformation, preventing aa-tRNA accommodation on the ribosome. We also show that didemnin B and ternatin-4 exhibit distinct effects on aa-tRNA selection that inform on observed disparities in their inhibition efficacies and physiological impacts. These integrated findings highlight the potential of single-molecule methods to reveal how distinct natural products differentially impact the human translation mechanism.
One step further: application of metabolomics techniques on the geographical indication (GI) registration process
Authors: Artêncio Mateus Manfrin , Cassago Alvaro Luis Lamas , Giraldi Janaina de Moura Engracia , Pádua Silvia Inês Dallavalle , Da Costa Fernando Batista 
Published: August 2022

PurposeA region can be registered as a geographical indication (GI) when its human or natural characteristics influence product attributes. However, GI registration is a complex process that can lead applicants to conflicts and resource waste. Since metabolomics can support product typicality, it can be an effective tool to evidence the place-product link, essential for GI registration. With the aim of increasing GI registration efficiency, this research aimed to map the Brazilian GI registration process from end to end, using business process model and notation (BPMN), and evaluate the application of metabolomics techniques as facilitator.Design/methodology/approachA qualitative exploratory study was proposed, with the Brazilian GI registration process as unit of analysis. Primary data was obtained through twelve in-depth interviews with GI producers, members of supporting institutions and metabolomics experts. Based on the collected data, the complete GI registration map was designed with bpmn.io software.FindingsResults provided a clear view of the GI registration process. Interviewees considered the selection of the appropriate GI category, the establishment of GI common rules, product specification and the confirmation of the place-product link as the most demanding requirements. Since the last two involve specifying the influence of the origin on products, the use of metabolomics was suggested as a powerful tool to complete these stages.Research limitations/implicationsThe theoretical contribution is provided by the interweave of the three scientific fields mentioned (GI, business process management (BPM) and metabolomics) to contribute to the still small body of literature on GI-related processes. Additionally, other theoretical contributions are the presentation of a GI registration map associated to the use of “omics” techniques as process facilitator.Practical implicationsThe practical contribution of this work is the establishment of an end-to-end view of the entire GI registration process, which makes easier for applicants to engage, plan resources and achieve the GI label. Furthermore, metabolomics acts as a facilitator since its data can be used for different purposes on the way to GI registration.Social implicationsResults can be used to facilitate GI registration, reducing resources demanded from applicants. GI labels provide product protection, better selling prices and competitive advantages for producers, which are positive outcomes in countries with a commodity-based economy like Brazil.Originality/valueThe originality of the study lies in the approach used to map the GI registration process, as well as the suggestion of metabolomics as facilitator in some of its stages.
Do multiple directorships stimulate or inhibit firm value? Evidence from an emerging economy
Authors: Alhaddad Lara , Gerged Ali Meftah , Saidat Zaid , Ali Al-Qudah Anas , Aziz Tariq 
Published: August 2022

PurposeThis study aims to examine the potential influence of multiple directorships (MDs) on the firm value of listed firms in Jordan.Design/methodology/approachUsing a sample of 1,067 firm-year observations of Jordanian listed companies from 2010 to 2020, this study applies a pooled ordinary least squares regression model to examine the above-stated relationship. This technique was supported by conducting a generalized method of moments estimation to address the possible occurrence of endogeneity concerns.FindingsThe results show a significant negative relationship between MDs and firm performance, thereby supporting the “Busyness Hypothesis”, which suggests that directors with MDs are expected to be over-committed, too busy and less vigilant. Thus, their ability to effectively monitor the company management on behalf of the shareholders is quite limited.Originality/valueTo the best of the authors’ knowledge, this is the first study in Jordan, and one of the very rare studies in the Middle Eastern and North African region, to examine the relationship between MDs and firm performance. This study provides important policy and practitioner implications in the field of corporate governance by highlighting the necessity of imposing stricter limits on the number of directorships allowed for board directors. Crucially, the empirical evidence implies that limited directorships ensure that directors are able to fulfil their board responsibilities appropriately, which is significantly associated with the firm value.
Digital responses of SMEs to the COVID-19 crisis
Authors: Giotopoulos Ioannis , Kontolaimou Alexandra , Tsakanikas Aggelos 
Published: August 2022

PurposeThis paper aims at exploring the factors that are important for the digital development of small and medium-sized enterprises (SMEs) in response to the coronavirus disease 2019 (COVID-19) crisis compared to large-sized enterprises.Design/methodology/approachUsing data from a survey in Greek firms during the pandemic, econometric models are estimated to identify factors that are related to the expansion of digital marketing and e-commerce practices of SMEs and large-sized enterprises based on the technology–organization–environment framework.FindingsThe results suggest that while further investments in information and communication technology (ICT) infrastructure are important for the digital development of SMEs during the COVID-19 crisis, it is the innovative activities that advance the digitalization of large-sized enterprises. Also, SMEs, which implement flexible human resource (HR) practices (such as remote work) and face delays in the supply chain due to the pandemic, appear to have increased probability of expanding their digital marketing and e-commerce. On the contrary, HR practices do not seem to matter for large firms, while new regulations appear to discourage their digital development during the COVID-19 crisis.Originality/valueThis is the first study which empirically explores the digital reactions of SMEs compared to those of large-sized enterprises in a pandemic crisis context. It advances the limited knowledge on the potentially different responses of SMEs and large-sized enterprises to major external shocks with respect to their digital marketing and e-commerce expansion.
Environmental collaboration with suppliers and cost performance: exploring the contingency role of digital orientation from a circular economy perspective
Authors: Chavez Roberto , Malik Mohsin , Ghaderi Hadi , Yu Wantao 
Published: August 2022

PurposeTo examine the interplay between sustainable supply chain management (SSCM) and circular economy, this research conceptualises and empirically tests an integrative framework of environmental information exchange with suppliers (ES), environmental product design (EPD) and cost performance (CP) with the contingency effect of digital orientation (DO). The associations proposed in the integrative framework provide a configuration of SSCM practices that support circular economy's restorative processes in the digital age.Design/methodology/approachThe resource orchestration theory and contingency theory are used to investigate the mediation and moderating effects, which were tested by a moderated mediation analysis of survey data of 100 firms in Australia.FindingsThe results show that EPD fully mediates the relationship between ES and CP. Further, DO was found to moderate the relationship between EPD and CP, but not the relationship between ES and EPD.Practical implicationsThe empirical findings of this study offer an effective SSCM practice configuration for firms seeking to target advanced circular business models and economic benefits. Managers should be aware that ES may not be enough to improve CP; EPD is a required mechanism to translate the ES benefits into cost superiority. Managers should also stimulate a DO culture to develop effective EPD capabilities, which leads to improved CP and a foundation for companies seeking to target circularity.Originality/valueThis study advances prior theoretical and practical knowledge. The authors propose and empirically test an integrated SSCM and circular economy model that incorporates mediation and moderation effects to clarify inconsistent findings in prior work, which provides a more holistic and practical understanding of SSCM practices in the digital context. Furthermore, the SSCM literature recommends the adoption of circular economy principles. The integrated model in this study provides a bridge between SSCM and circular economy.
Shikonin ameliorates oxidative stress and neuroinflammation via the Akt/ERK/JNK/NF‐κB signalling pathways in a model of Parkinson's disease
Authors: Guo Lei , Li Yuanyuan , Li Wenna , Qiu Jiaoxue , Du Juan , Wang Lingling , Zhang Ting 
Published: August 2022

AbstractParkinson's disease (PD) is the second most common neurodegenerative disorder. Shikonin plays protective roles in age‐associated diseases. Therefore, we investigate the biological functions of shikonin and its mechanisms involved in PD pathogenesis. The neurotoxin, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) was used to mimic PD‐like conditions in animal models. The learning and memory capacities were assessed by Morris water‐maze test, pole test, locomotor activity test and rotarod test. Neuroinflammation was determined by measuring the levels of tumour necrosis factor α (TNF‐α), interleukin (IL)‐1β, IL‐6, inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2). The quantification of superoxide dismutase, malondialdehyde and glutathione in substantia nigra was performed to estimate oxidative damage. Histopathologic changes were examined by haematoxylin and eosin staining. Immunofluorescence staining was conducted to determine the activation of astrocytes, tyrosine hydroxylase (TH)‐positive neurons, and nuclear translocation of p65. Immunohistochemistry was performed to evaluate dopamine transporter (DAT)‐positive neurons. Protein levels were measured by western blotting. Shikonin alleviates the cognitive and behavioural impairments. The death of dopaminergic neurons in nigra was attenuated by shikonin. The MPTP‐induced neuroinflammation and oxidative stress in substantia nigra were alleviated by shikonin administration. Shikonin ameliorated the neuronal damage in nigra and inhibited the activation of astrocyte. Shikonin modulated the protein kinase B (Akt)/extracellular regulated kinase (ERK)/c‐Jun N‐terminal kinase (JNK)/nuclear factor κB (NF‐κB) pathways. Shikonin ameliorates dopaminergic neuronal apoptosis by inhibiting oxidative stress and neuroinflammation via the Akt/ERK/JNK/NF‐κB pathways in PD. The study has several limitations. First, in a previous study, levels of phosphorylated ERK were increased by MPTP. In our current study, we observed decreased p‐ERK in nigra following MPTP treatment. Therefore, further investigation in the mechanisms of shikonin against PD progression is required. Second, the biological functions of shikonin need more exploration, including mitochondrial function and autophagy. Moreover, specific molecular targets for shikonin remain uncertain.
Can reading practitioners and researchers improve intensive reading support systems in a large urban school system?
Authors: Kearns Devin M. , Walker Melodee A. , Borges Jason C. , Duffy Meghan E. 
Published: August 2022

One way to provide intensive intervention for students with severe and persistent reading difficulties is to use a systematic data‐based decision‐making process called data‐based individualisation (DBI). DBI is a process for identifying needs and aligning them with specialist support. Meta‐analyses of DBI studies by university‐based researchers have shown positive effects, but university research studies do not involve many of the implementation science‐related factors that affect success. This study addresses the dearth of data from practice‐based studies that incorporate DBI and was done as a researcher–practitioner collaboration, developed with based on the theory that the collaborators' combined knowledge and skills could produce positive outcomes. Mixed methods were used to examine whether there was evidence of success in implementation DBI conducted through a researcher–practitioner partnership in New York City Public Schools, the largest public school system in the United States. Specifically, data were collected concerning the quality of DBI implementation and changes in teachers' and administrators' perspectives about the value of implementing intensive intervention. Results indicated that district‐level implementation met many criteria for effective DBI, that school teams (N = 6) implemented DBI with an overall high level of fidelity (mean score of 4.1 on a 5‐point scale) and that teachers and school administrators changed their thinking about intensive intervention as a result of participation in DBI. Stakeholder interview data indicated a high level of social acceptability for DBI implementation. Features of the research–practice partnership thought to have contributed to the success of the project are discussed.
Red wine coloration: A review of pigmented molecules, reactions, and applications
Authors: Zhang Xin‐Ke , Jeffery David W. , Li De‐Mei , Lan Yi‐bin , Zhao Xu , Duan Chang‐Qing 
Published: August 2022

AbstractColor is one of the most distinctive qualities of red wine. Despite new knowledge in the field of pigment identification, copigmentation, and oxidation being forthcoming, there is still a large gap between the fundamental research and practical winemaking outcomes. A state‐of‐art review from these two aspects is, therefore, necessary. This review first introduces updated knowledge about the primary pigments in wine, with emphasis on their physicochemical properties. Then, the mechanisms of copigmentation and oxidation are elucidated in detail, along with their relative contributions to wine color. Finally, the practical effects of copigmentation and micro‐oxygenation (MOX) in winemaking are summarized and discussed. In general, wine coloration is ultimately determined by the anthocyanin flavylium cation, which is greatly influenced by wine pH. In young red wine, grape‐derived anthocyanins and nonanthocyanin polyphenols (as copigments) are the foundation for wine coloration. During aging and storage, anthocyanin derivatives are formed via various chemical reactions, where moderate oxidation plays a vital role, whereas copigmentation constantly decreases. The essence of wine color evolution relates to the changes of physicochemical properties of primary pigments in wine, where the hydration equilibrium gradually diminishes. In practice, the effects of copigment addition and MOX during real vinification can be viewed as somewhat controversial, considering that many studies showed different effects on wine color and pigment concentration. Universal features can be summarized but some phenomena still remain unclear and deserve further exploration.
Greater self‐oriented and socially prescribed perfectionism in severe alcohol use disorder
Authors: Maurage Pierre , Creupelandt Coralie , Bollen Zoé , Pabst Arthur , Fontesse Sullivan , Laniepce Alice , Douilliez Céline 
Published: August 2022

AbstractBackgroundPerfectionistic individuals present exaggerated performance standards, generating a constant search for flawlessness and a high tendency to self‐criticize. Dominant models distinguish three dimensions of perfectionism: namely, self‐oriented, socially prescribed and other‐oriented. Perfectionism constitutes a vulnerability factor for psychopathological disorders, but its role in severe alcohol use disorder (SAUD) remains unexplored.MethodsSixty‐five recently detoxified patients with SAUD and 65 matched controls completed a perfectionism questionnaire (the Hewitt Multidimensional Perfectionism Scale), together with measures of psychopathology.ResultsSAUD was associated with greater self‐oriented and socially prescribed perfectionism, with no group differences on other‐oriented perfectionism. This differential pattern persisted when controlling for depression and anxiety levels, and there was no correlation with alcohol consumption.ConclusionThis specific perfectionistic profile is consistent with those of previous studies showing lower self‐evaluation (e.g., higher self‐blame and reduced self‐esteem) and impaired social cognition (e.g., unrealistic social standards and greater social isolation) in SAUD. In view of its potential role in the development and maintenance of SAUD, perfectionism may constitute a valuable treatment target in patients with this disorder.