bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic domain substitution for the high-throughput modification of non-ribosomal peptide analogues
Authors: Messenger Sarah R. , McGuinniety Edward M. R. , Stevenson Luke J. , Owen Jeremy G. , Challis Gregory L. , Ackerley David F. , Calcott Mark J. 
Published: June 2023

AbstractNon-ribosomal peptides are a diverse and medically important group of natural products. They are biosynthesised by modular non-ribosomal peptide synthetase (NRPS) assembly-lines in which domains from each module act in concert to incorporate a specific amino acid into a peptide. This modular biosynthesis has driven efforts to generate new peptide analogues by substituting amino acid specifying domains. Rational NRPS engineering has increasingly focused on using evolutionarily favoured recombination sites for domain substitution. Here, we present an alternative approach inspired by evolution, which involves large-scale diversification and screening. By adopting a metagenomic approach of amplifying amino acid specifying domains from metagenomic DNA derived from soil, we were able to substitute over 1,000 unique domains into a pyoverdine NRPS. To identify functional domain substitutions, we employed fluorescence and mass spectrometry screening techniques, followed by sequencing. This comprehensive screening process successfully identified more than 100 functional domain substitutions, resulting in the production of 16 distinct pyoverdines as major products. The significance of this metagenomic approach lies in its ability to shift the focus of engineering non-ribosomal peptide biosynthesis. Instead of relying on a high success rate of individual domain substitution, we have developed effective methods that enable the exploration of a broader range of substitutions. This opens new possibilities for the discovery and production of novel non-ribosomal peptides with diverse biological activities.Abstract Figure
Atg15 is a vacuolar phospholipase that disintegrates organelle membranes
Authors: Watanabe Yasunori , Iwasaki Yurina , Sasaki Kyoka , Suzuki Kuninori 
Published: June 2023

SummaryAtg15 (autophagy-related 15) is a vacuolar phospholipase essential for the degradation of cytoplasm-to-vacuole targeting (Cvt) bodies and autophagic bodies, hereinafter referred to as intravacuolar autophagic compartments (IACs), but it remains unknown if Atg15 directly disrupts IAC membranes. Here we show that the recombinantChaetomium thermophilumAtg15 lipase domain (CtAtg15(73–475)) possesses phospholipase activity that in acidic environments digests phospholipid to generate lysophospholipid and free fatty acid. The activity of CtAtg15(73–475) was markedly elevated by limited digestion with proteinase K. Proteinase K–treated CtAtg15(73–475) was detected as three fragments, with cleavage between S159 and V160, and between F209 and N210. We inserted the human rhinovirus 3C protease recognition sequence into the two sites and found that cleavage between S159 and V160 was important to activate CtAtg15(73–475). We confirmed that CtAtg15 compensated for the absence ofATG15inSaccharomyces cerevisiaecells, indicating that CtAtg15 could disintegrateS. cerevisiaeIACin vivo. Further, both mitochondria and IAC were disintegrated by CtAtg15 inS. cerevisiae. This study suggests that Atg15 can degrade any organelle membrane, indicating that Atg15 plays a role in disrupting organelle membranes delivered to vacuoles by autophagy.
Functional characterisation of rare variants in genes encoding the MAPK/ERK signalling pathway identified in long-lived Leiden Longevity Study participants
Authors: Hinterding Helena , Baghdadi Maarouf , Gehrmann Thies , Putter Pasquale , Neuerburg Mara , Lakenberg Nico , van den Akker Erik B. , Slagboom P. Eline , Deelen Joris , Partridge Linda 
Published: June 2023

AbstractHuman longevity, which is coupled to a compression of age-related disease, has been shown to be heritable. However, the number of identified common genetic variants linked to this trait remains small. This may indicate that longevity is, at least to some extent, determined by rare genetic variants that are potentially family-specific. We therefore investigated whole-genome sequencing data of long-lived families from the Leiden Longevity Study for family-specific variants. We identified variants residing in genes involved in the mitogen-activated protein kinase (MAPK) cascade, a lifespan-associated and evolutionarily conserved pathway emerging from studies in model organisms. We subsequently generated mouse embryonic stem cells (mESCs) harbouring these variants and conductedin vitrofunctional characterisation. Two variants, located inNF1(Phe1112Leu) andRAF1(Asp633Tyr), reduce MAPK/extracellular signal-regulated kinase (ERK) signalling pathway activity in mESCs. At the proteomic and transcriptomic level, we observed prominent changes that were shared (e.g. up-regulation of the ribosome) and opposing between the variants (e.g. down-regulation of mTORC1 signalling in the RAF1Asp633Tyrvariant cell line versus up-regulation in the NF1Phe1112Leuvariant cell lines). These metabolic changes were accompanied by an opposing effect of the variants on proliferation. Moreover, the RAF1Asp633Tyrvariant improved resistance to replication stress, while this was not the case for the NF1Phe1112Leuvariant. In conclusion, we identified two rare genetic variants in long-lived families that influence MAPK/ERK signalling in a manner that has previously been linked to increased lifespan in model organisms. Interestingly, we also observe some opposing and diverging effects between the variants, which indicates that they may either have some pleiotropic effects that are not relevant to longevity or that they target slightly different mechanisms to elicit their effects in mESCs. Our findings suggest that mESCs offer a good starting point forin vitrocharacterisation of rare genetic variants linked to human longevity and can be used to assess which of these variants to take forward toin vivostudies in model organisms.
Prenatal SARS-CoV-2 infection alters postpartum human milk-derived extracellular vesicles
Authors: Chutipongtanate Somchai , Cetinkaya Hatice , Zhang Xiang , Kuhnell Damaris , Benefield Desirée , Haffey Wendy , Wyder Michael , Patel Richa , Conrey Shannon C. , Burrell Allison R. , Langevin Scott , Nommsen-Rivers Laurie , Newburg David S. , Greis Kenneth D. , Staat Mary A. , Morrow Ardythe L. 
Published: June 2023

ABSTRACTHuman milk-derived extracellular vesicles (HMEVs) are crucial functional components in breast milk, contributing to infant health and development. Maternal conditions could affect HMEV cargos; however, the impact of SARS-CoV-2 infection on HMEVs remains unknown. This study evaluated the influence of SARS-CoV-2 infection during pregnancy on postpartum HMEV molecules. Milk samples (9 prenatal SARS-CoV-2 vs. 9 controls) were retrieved from the IMPRINT birth cohort. After defatting and casein micelle disaggregation, 1 mL milk was subjected to a sequential process of centrifugation, ultrafiltration, and qEV-size exclusion chromatography. Particle and protein characterizations were performed following the MISEV2018 guidelines. EV lysates were analyzed through proteomics and miRNA sequencing, while the intact EVs were biotinylated for surfaceomic analysis. Multi-Omics was employed to predict HMEV functions associated with prenatal SARS-CoV-2 infection. Demographic data between the prenatal SARS-CoV-2 and control groups were similar. The median duration from maternal SARS-CoV-2 test positivity to milk collection was 3 months (range: 1-6 months). Transmission electron microscopy showed the cup-shaped nanoparticles. Nanoparticle tracking analysis demonstrated particle diameters of <200 nm and yields of >1e11 particles from 1 mL milk. Western immunoblots detected ALIX, CD9 and HSP70, supporting the presence of HMEVs in the isolates. Thousands of HMEV cargos and hundreds of surface proteins were identified and compared. Multi-Omics predicted that mothers with prenatal SARS-CoV-2 infection produced HMEVs with enhanced functionalities involving metabolic reprogramming and mucosal tissue development, while mitigating inflammation and lower EV transmigration potential. Our findings suggest that SARS-CoV-2 infection during pregnancy boosts mucosal site-specific functions of HMEVs, potentially protecting infants against viral infections. Further prospective studies should be pursued to reevaluate the short- and long-term benefits of breastfeeding in the post-COVID era.
Subjective status perception of entrepreneurs and firm-level international behavior: evidence from Chinese private firms
Authors: Sheng Wei , Niu Zhiyong , Zhou Xiaoyan 
Published: June 2023

Purpose
The purpose of this paper is to explore the determinants of entrepreneurs’ subjective social status perception (SSP) on firm international behaviors based on the upper echelons theory and social class theory.

Design/methodology/approach
To test the hypotheses, the authors studied a large sample of 10,823 small- and medium-sized private Chinese enterprises from 2006 to 2014.

Findings
The results showed that entrepreneurs with higher status perception prefer international activity and firms have higher export intensity and intention. In addition, the social capital of entrepreneurs and institutional environment amplifies the positive relationship between SSP and international behavior.

Originality/value
This paper contributes to research on the upper echelon of management and extends our understanding of how managerial social characteristics influence international strategic decision-making. Besides, it also contributes to the emerging stream of social status research in international expansion studies and expand researchers’ limited understanding of the effects of social status in business settings.
Corruption, democracy and the location decisions of emerging multinationals: evidence from China’s cross-border mergers and acquisitions
Authors: Wang Jiang , Shen Xiaohua 
Published: June 2023

Purpose
This study investigated the moderating role of democracy in the relationship between corruption and foreign direct investment. The purpose of this study is to understand whether corruption has different effects on the location decisions of multinational enterprises (MNEs) depending on the regime type.

Design/methodology/approach
This study explored how institutional context influenced the impacts of corruption on the location decisions of MNEs, specifically using a sample of Chinese cross-border mergers and acquisitions between 2000 and 2020.

Findings
This study assessed the role of democracy in the relationship between corruption and the location decisions of Chinese MNEs. In general, this study found that Chinese MNEs were hindered by host country corruption, but that these detrimental effects were weaker in the presence of more effective democratic institutions.

Originality/value
This study contributes to the literature on institutional factors in international business through its simultaneous investigation of the effects of both democracy and corruption on the location decisions of MNEs. Moreover, there is a prevailing view that Chinese MNEs are willing to enter countries with high corruption, but the results of this study indicate that they are risk-averse in ways similar to their Western counterparts.
Application of a novel hybrid accumulation grey model to forecast total energy consumption of Southwest Provinces in China
Authors: Zhao Xuemei , Ma Xin , Cai Yubin , Yuan Hong , Deng Yanqiao 
Published: June 2023

PurposeConsidering the small sample size and non-linear characteristics of historical energy consumption data from certain provinces in Southwest China, the authors propose a hybrid accumulation operator and a hybrid accumulation grey univariate model as a more accurate and reliable methodology for forecasting energy consumption. This method can provide valuable decision-making support for policy makers involved in energy management and planning.Design/methodology/approachThe hybrid accumulation operator is proposed by linearly combining the fractional-order accumulation operator and the new information priority accumulation. The new operator is then used to build a new grey system model, named the hybrid accumulation grey model (HAGM). An optimization algorithm based on the JAYA optimizer is then designed to solve the non-linear parameters θ, r, and γ of the proposed model. Four different types of curves are used to verify the prediction performance of the model for data series with completely different trends. Finally, the prediction performance of the model is applied to forecast the total energy consumption of Southwest Provinces in China using the real world data sets from 2010 to 2020.FindingsThe proposed HAGM is a general formulation of existing grey system models, including the fractional-order accumulation and new information priority accumulation. Results from the validation cases and real-world cases on forecasting the total energy consumption of Southwest Provinces in China illustrate that the proposed model outperforms the other seven models based on different modelling methods.Research limitations/implicationsThe HAGM is used to forecast the total energy consumption of the Southwest Provinces of China from 2010 to 2020. The results indicate that the HAGM with HA has higher prediction accuracy and broader applicability than the seven comparative models, demonstrating its potential for use in the energy field.Practical implicationsThe HAGM(1,1) is used to predict energy consumption of Southwest Provinces in China with the raw data from 2010 to 2020. The HAGM(1,1) with HA has higher prediction accuracy and wider applicability compared with some existing models, implying its high potential to be used in energy field.Originality/valueTheoretically, this paper presents, for the first time, a hybrid accumulation grey univariate model based on a new hybrid accumulation operator. In terms of application, this work provides a new method for accurate forecasting of the total energy consumption for southwest provinces in China.
What’s love got to do with it? How does workplace romance provoke workplace ostracism and interpersonal conflict
Authors: Feng Ye , Rana Asif Mehmood , Bashir Hasnain , Sarmad Muhammad , Rasheed Anmol , Ayub Arslan 
Published: June 2023

Purpose
Extant research on workplace ostracism has investigated a victimization perspective to understand ostracism at the cost of examining the perpetrator-centric view of ostracism. This study aims to draw on the self-categorization theory and the social exchange theory to investigate the harmful effects of workplace romance in cultivating workplace ostracism from the perspective of perpetrator to combat concerns for victim blaming. This study further proposes that workplace ostracism triggered by workplace romance provokes interpersonal conflict. Besides, this study investigates the moderating role of prosocial behavior in the underlying linkages.

Design/methodology/approach
This study uses a multisource, time-lagged research design to collect data from employees working in the service sector organizations in Pakistan. This study analyzes 367 responses using SmartPLS (v 4.0).

Findings
The findings of this study reveal that workplace romance elicits workplace ostracism, which, in turn, fosters interpersonal conflict among coworkers. In addition, this study finds that ingroup prosocial behavior strengthens the associations between workplace romance and workplace ostracism, and workplace romance and interpersonal conflict, mediated by workplace ostracism such that the associations are more potent at higher levels of ingroup prosocial behavior and vice versa.

Originality/value
To the best of the authors’ knowledge, this is the first study that examines workplace romance as the perpetrator-centric antecedent of workplace ostracism, and ingroup prosocial behavior in exaggerating the outgroup ostracism and interpersonal conflict.
Organizational innovation and business model innovation: bridges from a systematic literature review
Authors: Perilla Maluche Ricardo Benjamín , Orozco Castro Luis Antonio 
Published: June 2023

Purpose
The purpose of this paper is to create a model that connects drivers between organizational innovation and business model innovation (BMI) to guide empirical research and the design of innovation management strategies.

Design/methodology/approach
The model was designed based on the results of a systematic literature review over the past 25 years that provides common predictor variables to build bridges between these two types of innovations.

Findings
It is a conceptual relationship between organizational innovation and BMI based on processes, new structures and customer relationship management. Moreover, there are five bridges from common predictors: strategy, top management, exploratory learning, technological innovation and environmental complexity.

Originality/value
The relationships between organizational innovation and BMI have been neglected in the literature. The model fills this gap by proposing hypotheses for empirical research and critical variables and relationships to steer organizational and business model innovation.
Tensile strengths of super high-strength steel strand wire ropes and wire rope open swaged socket connections at fire and post fire
Authors: Yamaguchi Takumi , Ozaki Fuminobu 
Published: June 2023

PurposeThe main purpose of this study was to evaluate the tensile strengths of JIS G3549 super high-strength steel strand wire ropes (1,570 MPa-class high-carbon steels) and wire rope open swaged socket connections at fire and post fire.Design/methodology/approachSteady-state tests from ambient temperature (20 °C) to 800 °C, transient-state tests under the allowable design tensile force and tensile tests in an ambient temperature environment after heating (heating temperatures of 200–800 °C) were conducted.FindingsThe tensile strengths of the wire rope and end-connection specimens at both fire and post fire were obtained. The steel wire rope specimens possessed larger reduction factors than general hot-rolled mild steels (JIS SS400) and high-strength steel bolts (JIS F10T). The end-connection specimens with sufficient socket lengths exhibited ductile fracture of the wire rope part at both fire and post fire; however, those with short socket lengths experienced a pull-out fracture at the socket.Originality/valueThe fundamental and important tensile test results of the super high-strength steel strand wire ropes (1,570 MPa-class high-carbon steels) and wire rope open swaged socket connections were accumulated at fire and post fire, and the fracture modes were clarified. The obtained test results contribute to fire resistance performance-based design of cable steel structures at fire and fire-damage investigations to consider their reusability post fire.
Human factor analysis of error detection and correction in hand-knotted carpet production process
Authors: Kaur Gagan Deep 
Published: June 2023

Purpose
The paper aims to discuss error detection and correction in Kashmiri carpet weaving (KCW), mediated by cryptographic code, Talim which is held to guarantee accurate information transference from designing to weaving, even after hundred years. Yet, carpets often show errors on completion.

Design/methodology/approach
Human factors analysis revealed error emergence, detection and correction in this practice whose task domains are distributed over large geographies (from in-premises to several kilometers) and timescales (from days to decades). Using prospective observation method, production process of two research carpets from their design, coding and weaving was observed while noting the errors made, identified and corrected by actors in each phase.

Findings
The errors were found to emerge, identified and corrected during different phases of designing, coding and weaving while giving rise to fresh errors in each phase, due to actors’ normal work routines.

Originality/value
In view of this, usual branding of “weaver-error” behind flawed carpet turns out to be misplaced value judgment passed in hindsight.
Design of a protocol model for the integration of social value in strategic management through social accounting
Authors: Echanove-Franco Alfonso , San-Jose Leire , Retolaza José Luis 
Published: June 2023

Purpose
This study aims to structure a model for integrating social value into strategic management based on identifying the critical success factors (CSF) for such integration in the investigated companies.

Design/methodology/approach
This research was based on the actor–network theory. Through a rigorous approach to the case study methodology in a two-stage process lasting 21 months, we carried out this study.

Findings
Companies that use the polyhedral social accounting model in their strategic management processes do so without a reference model. We identified CSF for integrating social value, which was incorporated into a protocol model based on stakeholder theory and the use of social accounting.

Practical implications
Practitioners can use the proposed model to maintain the alignment of strategic performance and purpose. Using social accounting based on indicators and financial proxies allows managers to incorporate social value into strategic management in terms of financial value.

Social implications
The institutional demand for social information is based on the growing sensitivity of companies. Aligning social values with business strategies contributes to social sustainability.

Originality/value
This study focuses on an unresearched emerging phenomenon. Since the first approach to stakeholder theory, the development of a stakeholder-oriented strategy has faced the lack of a stakeholder accounting system. The polyhedral model of social accounting could help overcome this problem as it provides information that allows a novel and innovative method to make a stakeholder-oriented strategy effective.
Real‐world safety and effectiveness of adalimumab in patients with hidradenitis suppurativa: A 52‐week analysis of a postmarketing surveillance study in Japan
Authors: Hayashi Nobukazu , Hayama Koremasa , Takahashi Kenzo , Kurokawa Ichiro , Okazaki Masateru , Kashiwagi Tomoko , Iwashita Eri , Terui Tadashi 
Published: June 2023

AbstractAdalimumab is a human monoclonal antibody against tumor necrosis factor‐α that was approved in Japan for the treatment of hidradenitis suppurativa (HS), a chronic recurrent inflammatory skin disease. We report the results of the final analysis of the postmarketing surveillance (PMS) study (ClinicalTrials.gov: NCT03894956), which evaluated the 52‐week safety and efficacy of adalimumab for HS treatment in real‐world clinical practice in Japan. This multicenter, prospective, open‐label, observational study (March 2019 to May 2021) included patients with HS treated with subcutaneous adalimumab at doses following the package insert. The primary endpoint was safety, and the secondary endpoints were effectiveness, including HS clinical response (HiSCR), C‐reactive protein (CRP), skin pain, and Dermatology Life Quality Index (DLQI). Of the 84 patients registered at 65 sites, 83 patients were included in the analyses. Adverse drug reactions (ADRs) were reported by 10 (12.0%) patients; two patients reported a serious ADR, including one patient with serious infection. Other safety events of special interest reported were liver disorder and dermatitis psoriasiform (one patient each). Almost all patients with ADRs were recovering or had recovered, except for one patient who experienced a serious ADR of liver disorder and died. At 12 weeks, 55.4% of patients achieved HiSCR; this increased to 60.5% and 62.8% at 24 and 52 weeks of adalimumab treatment, respectively. Significant reductions from baseline in CRP (P < 0.05), skin pain (P < 0.0001), and DLQI (P < 0.0001) were observed at all time points. The results from this PMS study demonstrated that long‐term adalimumab treatment is well tolerated and effective in patients with HS in real‐world clinical practice in Japan.