bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homocysteine-induced endoplasmic reticulum stress activates FGF21 via CREBH, resulting in browning and atrophy of white adipose tissue in Bhmt knockout mice
Authors: Warrier Manya , Paules Evan M. , Friday Walter B. , Bramlett Frances , Kim Hyunbae , Zhang Kezhong , Trujillo-Gonzalez Isis 
Published: September 2021

AbstractBetaine-homocysteine methyltransferase (BHMT) catalyzes the transfer of methyl-groups from betaine to homocysteine (Hcy) producing methionine and dimethylgycine. In this work, we characterize Bhmt wildtype (WT) and knockout (KO) mice that were fully backcrossed to a C57Bl6/J background. Consistent with our previous findings, Bhmt KO mice had decreased body weight, fat mass and adipose tissue weight compared to WT. Histological analyses and gene expression profiling indicate that adipose browning was activated in KO mice and contributed to the adipose atrophy observed. BHMT is not expressed in adipose tissue but is abundant in liver, thus, a signal must be originating from the liver that modulates adipose tissue. We found that, in Bhmt KO mice, homocysteine-induced endoplasmic reticulum (ER) stress, with activation of hepatic transcription factor cyclin AMP response element binding protein (CREBH), mediated an increase in hepatic and plasma concentrations of fibroblast growth factor 21 (FGF21), which is known to induce adipose browning. CREBH binds to the promoter regions of FGF21 to activate its expression. Taken together, our data indicate that deletion of a single gene in one-carbon metabolism modifies adipose biology and energy metabolism. It would be interesting to determine whether people with functional polymorphisms in BHMT exhibit a similar adipose atrophy phenotype.
Digital Spatial Profiling of Collapsing Glomerulopathy
Authors: Smith Kelly D. , Henriksen Kammi , Nicosia Roberto F. , Alpers Charles E. , Akilesh Shreeram 
Published: September 2021

ABSTRACTCollapsing glomerulopathy is a histologically distinct variant of focal and segmental glomerulosclerosis that presents with heavy proteinuria and portends a poor prognosis. Collapsing glomerulopathy can be triggered by viral infections such as HIV and SARS-CoV-2. Transcriptional profiling of collapsing glomerulopathy lesions is difficult since only a few glomeruli may exhibit this histology within a kidney biopsy and the mechanisms driving this heterogeneity are unknown. Therefore, we used recently developed digital spatial profiling (DSP) technology which permits quantification of mRNA at the level of individual glomeruli. Using DSP, we profiled 1,852 transcripts in glomeruli from HIV and SARS-CoV-2 infected patients with biopsy confirmed collapsing glomerulopathy. The increased resolution of DSP uncovered heterogeneity in glomerular transcriptional profiles that were missed in early laser capture microdissection studies of pooled glomeruli. Focused validation using immunohistochemistry and RNA in situ hybridization showed good concordance with DSP results. Therefore, DSP represents a powerful method to dissect transcriptional programs of pathologically discernible kidney lesions.
Interplay between mitochondria and reactive oxygen and nitrogen species in metabolic adaptation to hypoxia in facioscapulohumeral muscular dystrophy: potential therapeutic targets
Authors: Heher P , Ganassi M , Weidinger A , Engquist EN , Pruller J , Nguyen TH , Tassin A , Declèves AE , Mamchaoui K , Grillari J , Kozlov AV , Zammit PS 
Published: September 2021

AbstractFacioscapulohumeral muscular dystrophy (FSHD) is characterised by descending skeletal muscle weakness and wasting. FSHD is caused by mis-expression of the transcription factor DUX4, which is linked to oxidative stress, a condition especially detrimental to skeletal muscle with its high metabolic activity and energy demands. Oxidative damage characterises FSHD and recent work suggests metabolic dysfunction and perturbed hypoxia signalling as novel pathomechanisms. However, redox biology of FSHD remains poorly understood, and integrating the complex dynamics of DUX4-induced metabolic changes is lacking.Here we pinpoint the kinetic involvement of altered mitochondrial RONS metabolism and impaired mitochondrial function in aetiology of oxidative stress in FSHD. Transcriptomic analysis in FSHD muscle biopsies reveals strong enrichment for pathways involved in mitochondrial complex I assembly, nitrogen metabolism, oxidative stress response and hypoxia signalling. We found elevated ROS levels correlate with increases in steady-state mitochondrial membrane potential in FSHD myogenic cells. DUX4 triggers mitochondrial membrane polarisation prior to oxidative stress generation and apoptosis through mitochondrial ROS, and affects NO· bioavailability via mitochondrial peroxidation. We identify complex I as the primary target for DUX4-induced mitochondrial dysfunction, with strong correlation between complex I-linked respiration and cellular oxygenation/hypoxia signalling activity in environmental hypoxia. Thus, FSHD myogenesis is uniquely susceptible to hypoxia-induced oxidative stress as a consequence of metabolic mis-adaptation. Importantly, mitochondria-targeted antioxidants rescue FSHD pathology more effectively than conventional antioxidants, highlighting the central involvement of disturbed mitochondrial RONS metabolism. This work provides a pathomechanistic model by which DUX4-induced changes in oxidative metabolism impair muscle function in FSHD, amplified when metabolic adaptation to varying O2 tension is required.HighlightsTranscriptomics data from FSHD muscle indicates enrichment for disturbed mitochondrial pathwaysDisturbed RONS metabolism correlates with mitochondrial membrane polarisation and myotube hypotrophyDUX4-induced changes in mitochondrial function precede oxidative stress through mitoROS and affect hypoxia signalling via complex IFSHD is sensitive to environmental hypoxia, which increases ROS levels in FSHD myotubesHypotrophy in hypoxic FSHD myotubes is efficiently rescued with mitochondria-targeted antioxidantsGraphical abstract
Methods for the targeted sequencing and analysis of integrons and their gene cassettes from complex microbial communities
Authors: Ghaly Timothy M. , Penesyan Anahit , Pritchard Alexander , Qi Qin , Rajabal Vaheesan , Tetu Sasha G. , Gillings Michael R. 
Published: September 2021

AbstractIntegrons are bacterial genetic elements that can integrate mobile gene cassettes. They are mostly known for spreading antibiotic resistance cassettes among human pathogens. However, beyond clinical settings, gene cassettes encode an extraordinarily diverse range of functions important for bacterial adaptation. The recovery and sequencing of cassettes has promising applications, including: surveillance of clinically important genes, particularly antibiotic resistance determinants; investigating the functional diversity of integron-carrying bacteria; and novel enzyme discovery. Although gene cassettes can be directly recovered using PCR, there are no standardised methods for their amplification and, importantly, for validating sequences as genuine integron gene cassettes. Here, we present reproducible methods for the PCR amplification, sequence processing, and validation of gene cassette amplicons from complex communities. We describe two different PCR assays that either amplify cassettes together with integron integrases, or gene cassettes together within cassette arrays. We compare the use of Nanopore and Illumina sequencing, and present bioinformatic pipelines that filter sequences to ensure that they represent amplicons from genuine integrons. Using a diverse set of environmental DNAs, we show that our approach can consistently recover thousands of unique cassettes per sample and up to hundreds of different integron integrases. Recovered cassettes confer a wide range of functions, including antibiotic resistance, with as many as 300 resistance cassettes found in a single sample. In particular, we show that class 1 integrons appear to be collecting and concentrating antibiotic resistance genes out of the broader diversity of cassette functions. The methods described here can be applied to any environmental or clinical microbiome sample.
MOLECULAR VIDEOGAMING: SUPER-RESOLVED TRAJECTORY-BASED NANOCLUSTERING ANALYSIS USING SPATIO-TEMPORAL INDEXING
Authors: Wallis Tristan P. , Jiang Anmin , Hou Huiyi , Gormal Rachel S. , Durisic Nela , Balistreri Giuseppe , Joensuu Merja , Meunier Frédéric A. 
Published: September 2021

ABSTRACTSingle-molecule localization microscopy (SMLM) techniques are emerging as vital tools to unravel the nanoscale world of living cells. However, current analysis methods primarily focus on defining spatial nanoclusters based on detection density, but neglect important temporal information such as cluster lifetime and recurrence in “hotspots” on the plasma membrane. Spatial indexing is widely used in videogames to effectively detect interactions between moving geometric objects. Here, we use the R-tree spatial indexing algorithm to perform SMLM data analysis and determine whether the bounding boxes of individual molecular trajectories overlap, as a measure of their potential membership in nanoclusters. Extending the spatial indexing into the time dimension allows unique resolution of spatial nanoclusters into multiple spatiotemporal clusters. We have validated this approach using synthetic and SMLM-derived data. Quantitative characterization of recurring nanoclusters allowed us to demonstrate that both syntaxin1a and Munc18-1 molecules transiently cluster in hotspots on the neurosecretory plasma membrane, offering unprecedented insights into the dynamics of these protein which are essential to neuronal communication. This new analytical tool, named Nanoscale Spatiotemporal Indexing Clustering (NASTIC), has been implemented as a free and open-source Python graphic user interface.
A thermodynamic model for interpreting tryptophan excitation-energy-dependent fluorescence spectra provides insight into protein conformational sampling and stability
Authors: Kwok A , Camacho IS , Winter S , Knight M , Meade RM , Van der Kamp MW , Turner A , O’Hara J , Mason JM , Jones AR , Arcus VL , Pudney CR 
Published: September 2021

ABSTRACTIt is now over thirty years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. Whilst there have been many key efforts in the intervening years, a biophysical thermodynamic model to quantify the relationship between the REES effect and protein flexibility has been lacking. Without such a model the full potential of the REES effect cannot be realized. Here, we present a thermodynamic model of the protein REES effect that captures information on protein conformational flexibility, even with proteins containing multiple tryptophan residues. Our study incorporates exemplars at every scale, from tryptophan in solution, single tryptophan peptides to multi-tryptophan proteins, with examples including a structurally disordered peptide, de novo designed enzyme, human regulatory protein, therapeutic monoclonal antibody in active commercial development, and a mesophilic and hyperthermophilic enzyme. Combined, our model and data suggest a route forward for the experimental measurement of the protein REES effect and point to the potential for integrating bimolecular simulation with experimental data to yield novel insights.
A thermostable oral SARS-CoV-2 vaccine induces mucosal and protective immunity
Authors: Bellier Bertrand , Saura Alicia , Luján Lucas A. , Molina Cecilia R. , Lujan Hugo D. , Klatzmann David 
Published: September 2021

AbstractAn ideal protective vaccine against SARS-CoV-2 should not only be effective in preventing disease, but also in preventing virus transmission. It should also be well accepted by the population and have a simple logistic chain. To fulfill these criteria, we developed a thermostable, orally administered vaccine that can induce a robust mucosal neutralizing immune response. We used our platform based on retrovirus-derived enveloped virus-like particles (e-VLPs) harnessed with variable surface proteins (VSPs) from the intestinal parasite Giardia lamblia, affording them resistance to degradation and the triggering of robust mucosal cellular and antibody immune responses after oral administration. We made e-VLPs expressing various forms of the SARS-CoV-2 Spike protein (S), with or without membrane protein (M) expression. We found that prime-boost administration of VSP-decorated e-VLPs expressing a pre-fusion stabilized form of S and M triggers robust mucosal responses against SARS-CoV-2 in mice and hamsters, which translate into complete protection from a viral challenge. Moreover, they dramatically boosted the IgA mucosal response of intramuscularly injected vaccines. We conclude that our thermostable orally administered e-VLP vaccine could be a valuable addition to the current arsenal against SARS-CoV-2, in a stand-alone prime-boost vaccination strategy or as a boost for existing vaccines.
Multiple motors cooperate to establish and maintain acentrosomal spindle bipolarity inC. elegansoocyte meiosis
Authors: Cavin-Meza Gabriel , Kwan Michelle M. , Wignall Sarah M. 
Published: September 2021

ABSTRACTWhile centrosomes organize spindle poles during mitosis, oocyte meiosis can occur in their absence. Spindles in human oocytes frequently fail to maintain bipolarity and consequently undergo chromosome segregation errors, making it important to understand mechanisms that promote acentrosomal spindle stability. To this end, we have optimized the auxin-inducible degron system inC. elegansto remove factors from pre-formed oocyte spindles within minutes and assess effects on spindle structure. This approach revealed that dynein is required to maintain the integrity of acentrosomal poles; removal of dynein from bipolar spindles caused pole splaying, and when coupled with a monopolar spindle induced by depletion of kinesin-12 motor KLP-18, dynein depletion led to a complete dissolution of the monopole. Surprisingly, we went on to discover that following monopole disruption, individual chromosomes were able to reorganize local microtubules and re-establish a miniature bipolar spindle that mediated chromosome segregation. This revealed the existence of redundant microtubule sorting forces that are undetectable when KLP-18 and dynein are active. We found that the kinesin-5 family motor BMK-1 provides this force, uncovering the first evidence that kinesin-5 contributes toC. elegansmeiotic spindle organization. Altogether, our studies have revealed how multiple motors are working synchronously to establish and maintain bipolarity in the absence of centrosomes.
The impact of firm innovativeness on consumer trust in the sharing economy: a moderated mediation model
Authors: Geng Ruoshi , Sun Ruijie , Li Jie , Guo Fan , Wang Wangshuai , Sun Gong 
Published: September 2021

PurposeThis paper examined the relationship between firm innovativeness and consumer trust in the sharing economy. In addition, the authors examine the mediating effect of organizational legitimacy and the moderating effect of social worth.Design/methodology/approachTo examine the hypotheses, the authors collected data from 276 users of a sharing platform (Didi) in China to conduct empirical research. The “lavaan” packages in R and SPSS were used to analyze the data and test the proposed hypotheses.FindingsThe results reveal that sharing platforms' innovativeness is positively related to consumer trust, and this relationship is mediated by organizational legitimacy. Furthermore, sharing platforms' social worth moderates the relationship between firm innovativeness and organizational legitimacy as well as the indirect effect of firm innovativeness on consumer trust via organizational legitimacy.Practical implicationsThis article proposes strategies that enable sharing platforms to increase consumer trust, which can also better promote the development of the sharing economy.Originality/valueThis paper contributes to the literature by focusing on the social attributes of the sharing economy. By building a more detailed model of consumer trust, this paper adds to the knowledge on the influencing mechanism of consumer trust in the sharing economy.
Factors affecting the diffusion of traceability practices in an imported fresh produce supply chain in China
Authors: Yi Ying , Bremer Phil , Mather Damien , Mirosa Miranda 
Published: September 2021

PurposeThe purpose of this paper is to facilitate the successful adoption of traceability technologies, such as blockchain, into food supply chains and facilitate the understanding of the barriers and enablers to their uptake by channel members' needs so that appropriate enabling strategy can be put in place.Design/methodology/approachIn this paper, an integrated framework involving five components was used as the methodology: (1) diffusion of innovation theory, (2) the innovation concept, (3) the business structure-conduct-performance paradigm, (4) legitimacy and (5) trust was developed and assessed for validity through interviewing 21 channel members, including distributors, wholesalers, Internet retailers and traditional retailers associated with a global fresh produce company's supply chain in China.FindingsBarriers negatively framing channel members' attitudes and decisions included a perceived lack of need owing to fresh produce having a short shelf life and being of low value and risk. However, the importance of traceability and the need for effective food recalls were not always understood among channel members, and distributed trust innovations were also suppressed by their lack of compatibility with the Chinese hierarchical culture.Originality/valueTo date, channel members' perception of innovations in food supply chains has not been considered in light of the components proposed in the integrated framework. The adapted framework used in this study ensured a comprehensive assessment of channel members' attitude and motivations toward traceability practices.
The interrelatedness of organizational ambidexterity, dynamic capabilities and open innovation: a conceptual model towards a competitive advantage
Authors: van Lieshout Johannes W.F.C. , van der Velden Jeroen M. , Blomme Robert J. , Peters Pascale 
Published: September 2021

PurposeEstablishing a competitive advantage in today's dynamic environment involves optimizing an organization's exploration and exploitation strategy. This paper aims to explore how an open innovation strategy complements the organization's ambidextrous strategy in attaining a competitive advantage. Organizational ambidexterity and dynamic capability theories are also explored to investigate the impact of open innovation on the organization's ambidextrous strategy and competitive advantage – especially inbound and outbound open innovation.Design/methodology/approachThe authors conducted a systematic literature review using Boolean search techniques, which was focused on the research fields of the sub-areas of general management, strategy, innovation, organization studies, information management, entrepreneurship, international business, marketing, and economics, supplemented by the snowball technique.FindingsOrganizations that combine their ambidextrous strategy with open innovation attributes achieve a competitive advantage through developing their dynamic capabilities by which organizations change their value proposition. This study also shows that an ambidextrous strategy should no longer be viewed as a structural solution implemented by management, but also as a bottom-up intervention. Additionally, the authors found that the organization's dynamic capabilities establish a feedback loop, which changes the organization's ambidextrous strategy to resolve the efficiency–agility paradox.Originality/valuePrevious research has focused on strategic orientation; however, hardly any research has investigated how the interrelatedness of open innovation, organizational ambidexterity and dynamic capabilities support a competitive advantage. The authors present a conceptual model that inspires new research avenues.
Modeling and analysis of a quality traceability framework for phosphate extraction process: evidence from Morocco
Authors: Lafquih Hind , Lissane Elhaq Saad , Krimi Issam , Berquedich Mouna 
Published: September 2021

PurposeAccording to United Nations reports, the worldwide population is expected to reach around 9.6 billion by 2050. This forecasting emphasizes the role of phosphate-based fertilizers for developing sustainable agriculture and ensures the demand all over the planet. From this perspective, phosphate companies are racing to improve their industrial performance and guarantee the quality, reliability and integrity of information efficiently. The purpose of this paper is to propose a traceability system framework that ensures product quality tracing and real-time operations monitoring for open-pit mines.Design/methodology/approachThe authors develop a hybrid approach that integrates Business Process Model and Notation techniques with System Modeling Language to formalize several use cases and scenarios to model quality traceability processes related to open-pit mines. This framework also embeds an optimization module based on mathematical modeling approaches to optimize stockpiles’ movement and respect the distinction between different qualities.FindingsThis paper explains a successful implementation of a quality traceability tool for an African mining company. The research team was able to understand and scale down the problem faced by the managers. Further, the study is focused on improving quality tracing over time and automatizing the current compliance processes related to the mine extraction activities. The proposed tool is proved highly effective in reducing the time of tracing quality claims by 46% compared with the manual procedure. Second, the implementation of this tool reduced fuel costs by 34% and CO2 emissions by 10%.Originality/valueThe originality of the contributions lies in four aspects: (1) adapting quality traceability concept for the mining industry; (2) assessing the current trends of traceability systems considering the mining industry context; (3) hybridizing business processes re-engineering, quality system and optimization modeling; and (4) using a real case study of a phosphate company to evaluate the framework.
Assessing universities’ social sustainability: accounting for stakeholder value
Authors: Ayuso Silvia , Carbonell Xavier , Serradell Laia 
Published: September 2021

Purpose
The purpose of this paper is to assess higher education institutions’ (HEIs) social sustainability by applying Integrated Social Value (ISV) analysis to eight universities belonging to the Catalan Association of Public Universities in Spain.

Design/methodology/approach
ISV analysis is a social accounting methodology that considers both the economic value and the social value created for all the organisation’s stakeholders through a participatory and systematic process.

Findings
The authors have shown that ISV analysis can be effective to assess the impacts on social sustainability of HEIs. The monetised results facilitate understanding about the valued impacts and allow integration with the universities’ financial data.

Research limitations/implications
The research advances the under-researched topic of social sustainability assessment in higher education.

Practical implications
Quantifying universities’ social impacts in monetary terms may help to transform conventional financial accounting and improve HEIs’ internal strategy and management according to sustainability principles.

Social implications
The process of measuring the social value created by universities provides a way to meet the rising demands for greater accountability and transparency and facilitates engagement with stakeholders on how these institutions are contributing to sustainable development.

Originality/value
ISV analysis represents an innovative approach to assess how HEIs create benefits for its internal and external stakeholders and contribute to solutions to social challenges.