Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a critical public health concern due to the limited efficacy of the Bacillus Calmette-Guerin (BCG) vaccine, the only WHO-approved vaccine so far. Based on the reverse vaccinology approach, this study involves in silico prediction of a fusion constructed from four highly immunogenic antigens from the latent, early, and active stages of the disease. The fusion named TetraFuVac11 consists of the complete sequences of the antigens CFP-7 and EspC and the truncated sequences of the antigens HspX and Hrp1. Major Histocompatibility Complex II (MHC II) binding Th-cell-specific epitopes were predicted through tools provided in the Immune Epitope Database (IEDB). The designed fusion molecule was found to be antigenic, non-allergenic and non-toxic. The instability index II and the GRAND Average of Hydropathy values were predicted to be 29.51 and -0.182, respectively. The refinement of the predicted 3D structure resulted in an improved stereochemical profile. The Z-score was predicted to be -6.8, and the ERRAT score was improved from 94.928 for the unrefined model to 97.1591 for the refined model. The data obtained from molecular dynamics (MD) simulations and Normal Mode Analysis (NMA) of the docked complex between the refined fusion protein and Toll-like Receptor 4 (TLR4) demonstrated a s interaction. The fusion construct was successfully predicted to be cloned into the pET-28a(+) vector to make a recombinant plasmid. The predicted solubility of the fusion protein exceeded the threshold values, indicating soluble expression in Escherichia coli. Finally, based on the encouraging in silico data, the proposed construct could serve as a potential vaccine candidate for detailed experimental validation towards developing an Mtb-specific vaccine.
Using social information processing theory, our paper develops and tests a multilevel moderated mediation model that investigates the interrelationships of developmental human resource management (DHRM), affective organizational commitment (AOC), loyal boosterism, proactive customer service performance (PCSP), and leader conscientiousness. Data came from hotel frontlines employees (FLEs) and their supervisors in Morocco. The results from structural equation modeling suggest that all hypotheses were corroborated. As hypothesized, DHRM practices fostered FLEs' loyal boosterism and PCSP. As expected, AOC partly mediated the impacts of DHRM practices on loyal boosterism and PCSP. Consonant with the study hypotheses, leader conscientiousness strengthened the positive influences of DHRM practices on AOC, while it moderated the effects of DHRM practices on loyalt boosterism and PSCP via AOC. These results ensure significant insights for boosting DHRM practices and their outcomes to reach customer satisfaction and retention. These results also ensure significant implications for theory and offer future research directions.
Drawing on the motivational information processing theory, our paper developed and tested a moderated mediation model of whistleblowing. Specifically, our paper tests: (1) the effect of perceived overqualification (POQ) on whistleblowing intention; (2) prosocial motivation as a mediator between POQ and whistleblowing intention; (3) high involvement work practices (HIWPs) as a moderator between POQ and whistleblowing intention; and (4) HIWPs as a moderator of the influence of POQ on said outcome via prosocial motivation. The results from the partial least squares structural equation modeling suggest that overqualified employees who are pro-socially motivated display proclivity to whistle blow. More importantly, HIWPs strengthen the positive impact of POQ on propensity to whistle blow via prosocial motivation such that this positive impact is stronger among employees high on HIWPs than employees low on HIWPs. All the hypothesized links were corroborated, and the research model proposed in this paper was viable.
Tumor-related inflammatory mediators play a vital role in the host tumor defense response by intensifying tumor growth and evading the immune response. For the first time, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) and multiplex-based proteomic approach was utilized for the profiling of acute response proteins in RCC patients from Pakistan. We evaluated the potential role of inflammatory modifiers in RCC and adjacent normal samples using DAVID, GAD, and enriched KEGG pathways. Databases revealed the association of enriched KEGG pathways with dataset proteins involved in bladder cancer, transcriptional misregulation, proteoglycans, and microRNAs in cancer, suggesting the potential roles of these mediators in tumorigenesis. A panel of six proteins were quantified by multiplexed bead assay in the sera of samples with hepatocyte growth factor (HGF), tissue inhibitor of metalloproteinases-1 TIMP1, TIMP4, apolipoprotein A1 (APOA1), ferritin (FR), and osteopontin (OPN). Our results indicated that OPN, APOA1, and TIMP4 in particular possess high potential in discriminating RCC subjects from healthy individuals (P < 0.0001) with the area under the ROC curve (AUC) > 0.96. The differential expression of inflammatory proteins is associated with tumor progression and may serve as potential biomarkers of RCC.
Amid rising AI-powered chatbot adoption in hospitality and tourism, this study explores how chatbot negative experiences shape brand hate and outcomes. Drawing upon stimulus-organism-response theory, we examine brand irritation, brand-indistinctiveness, and consumer helplessness as antecedents of brand hate, desire for detachment-(DD), and desire to participate in online firestorms-(OF) as coping responses/outcomes. The moderating role of negative affectivity on brand hate and its antecedents is examined. This research adopts a mixed-method approach, comprising interviews with 34 users and data collection from 484 Chinese participants. The results established the role of brand hate as a mediator between irritation, helplessness, and subsequent outcomes. Additionally, negative affectivity is found to moderate the relationships in question significantly. This study contributes to hospitality management, brand management, and chatbot development by enhancing our understanding of consumer experiences in this context. It represents a pioneering effort to integrate negative experiences with chatbots within the framework of consumer brand hate.
Because research on responsible leadership has grown significantly in recent years, we conducted a systematic review of research on responsible leadership. Our overall goal was to establish a comprehensive understanding of alternative definitions of responsible leadership, its theoretical foundations, and distinctions from other moral leadership constructs. Drawing from 194 studies, we first clarify the conceptual underpinnings of responsible leadership, and how it differs from other constructs in the moral leadership domain, thus highlighting its value as a construct. Second, we identify and evaluate the prominent theoretical frameworks that underpin responsible leadership. Third, we conceptualize the antecedents, mediating factors, contingency variables and outcomes of responsible leadership. Fourth, we offer important recommendations for future research that will move the field forward. Overall, our review provides insights to advance an understanding of responsible leadership.
Our paper develops and tests a moderated mediation model of despotic leadership (DL) and knowledge sabotage behavior (KSB). The model assesses: (a) the link between DL and KSB; (b) emotional dissonance as a mediator between DL and KSB; (c) willpower and waypower as the two moderators of the effect of DL on the aforesaid undesirable outcome; and (d) willpower and waypower as the two moderators of the effect of DL on KSB via emotional dissonance. To gauge these relationships, we used time-lagged data obtained from hotel frontline employees. Most of the hypothesized associations are supported, and the model we proposed is viable. Managers' DL heightens employees' KSBs, and emotional dissonance mediates this link. FLEs' waypower reduces the detrimental effect of DL on KSB. Waypower also mitigates the deleterious effect of DL on the said outcome via emotional dissonance.
Given the importance of growth hacking for the long-term success of businesses and the lack of empirical research, we draw on dynamic capability theory to propose a model that explicates how and when entrepreneurial leadership leads to growth hacking adoption in the startup context. Two studies were conducted to test the proposed model. Specifically, in Study 1, we developed a 15-item scale (five dimensions) of growth hacking adoption based on 207 responses from the owners of various startups in Morocco. Study 2 was based on time-lagged data from 305 owners of startups in China. Our results reveal that entrepreneurial leadership positively impacts growth hacking adoption directly and via big data capability and organizational learning ambidexterity. Further, leader conscientiousness moderates the effects of entrepreneurial leadership on big data capability. We provide actionable insights for owners/managers of start-ups to foster learning ambidexterity and drive growth hacking.
Little is known about the mediators, moderators, and consequences of technological innovation in the hospitality literature that would help the hotel to amplify its competitiveness. Therefore, using the resource-based view as the theoretical focus, our paper develops and tests a moderated mediation model that examines individual ambidexterity as a mediator between technological innovation (TIN) and service performance, responsible leadership (RL) as a moderator of the impact of TIN on individual ambidexterity, and RL as a moderator of the indirect impact of TIN on service performance via individual ambidexterity. Data gathered from hotel employees in China were used to assess said associations via the partial least squares structural equation modeling. As hypothesized, individual ambidexterity functions as the underlying mechanism relating TIN to service performance. RL moderates the positive impact of TIN on individual ambidexterity. More importantly, RL strengthens the indirect positive influence of TIN on service performance via individual ambidexterity.
Using cognitive-motivational-relational theory as the theoretical focus, our paper develops and tests a research model that investigates workplace anxiety and work alienation as the serial mediators of the influence of exploitative leadership (EL) on service sabotage. Data were collected from hotel frontline employees (FLEs) with a time lag of one month and their supervisors. The hypotheses were assessed via the PROCESS macro. The results reveal that EL exacerbates workplace anxiety, which in turn leads to FLEs' service sabotage. The results further demonstrate that work alienation mediates the link between EL and service sabotage. As hypothesized, the ELservice sabotage relationship is serially mediated by workplace anxiety and work alienation. Our research contributes to the hospitality and dark leadership literatures by denoting workplace anxiety and work alienation as the underlying processes through which exploitative leaders trigger employees' service sabotage.
Recombinant DNA technology is widely used to produce industrially and pharmaceutically important proteins. In silico analysis, performed before executing wet lab experiments has been greatly helpful in this connection. A shift in protein analysis has been observed over the past decade, driven by advancements in bioinformatics databases, tools, software, and web servers. Several bioinformatics tools and resources are available for predicting a protein's structural and functional relationship. Insights into the proteins' structure and function are important for drug discovery, development, and enhancing the suitability of the recombinant enzymes/proteins for industrial applications. This review compares and discusses various computational tools that provide structural and functional insights into recombinant proteins, including genome mining, sequence alignment, topological arrangement, physicochemical properties, including solubility and stability, site-directed mutagenesis, protein design and engineering, ligand binding interactions through molecular docking, and molecular dynamics simulation. This comparative study explores the utilisation of different computational tools, software, and web servers with their principles, algorithms, and outcomes. This document would be a milestone for the scientists to select suitable computational approaches to plan and improve the outcome for achieving the desired targets.
Alpha-amylases are essential enzymes that cleave α-1,4-glycosidic bonds in starch, generating products such as glucose, maltose, dextrin's, and oligosaccharides, which play a key role in various industries. The structural and functional insights, along with biochemical dynamics, of Bacillus licheniformis α-amylase variants (BLAMWSP and BLAMCD) were investigated through N- and C-terminal truncations along with two previously reported mutations, Thr353Ile and His400Arg. MD simulation results demonstrated the stability of binding and catalytic residues as predicted through molecular docking. Analysis of the secondary structure and temperature ramping through CD spectroscopy revealed that both BLAMWSP and BLAMCD maintained structural stability at 90 °C. The specific activities of BLAMWSP and BLAMCD against wheat starch were determined to be 2343.09 ± 0.20 and 4237.88 ± 0.66 (μmol min-1/μmole protein), respectively at 90 °C in 100 mM phosphate buffer (pH 6.0). The BLAMCD variant exhibited a two-fold increase in enzymatic activity relative to BLAMWSP due to increased surface accessibility of its substrate-binding and catalytic residues. The enzymes' catalytic efficiencies (kcat /Km) were 51.76 ± 1.76 and 114.10 ± 1.41, highlighting that BLAMCD exhibits significantly higher catalytic efficiency and substrate affinity than BLAMWSP. These modifications make BLAMCD a promising candidate for industrial starch liquefaction and scarification applications.
Based on social information processing, this study investigates the indirect effects of individual ambidexterity on the relationship between responsible leadership and sustainable outcomes (sustainable economic performance, sustainable social performance, and sustainable financial performance). Additionally, we investigate the moderating influence of knowledge-sharing culture on the link between responsible leadership and individual ambidexterity. Furthermore, we also investigated knowledge-sharing culture to moderate the mediation link. Data collected from employees in service sector organisations across two distinct studies (Study 1, n = 241; Study 2, n = 251), were analyzed using Smart PLS 4.0. Our findings substantiate that individual ambidexterity serves as a mediator in the relationship between responsible leadership and outcomes (sustainable economic performance, sustainable social performance, and sustainable financial performance). Further, the study demonstrates that knowledge-sharing culture amplifies the positive association between responsible leadership and individual ambidexterity. Furthermore, the study demonstrates that knowledge-sharing culture amplifies the mediation relationship as well. This study contributes to the existing knowledge on responsible leadership in the hospitality sector by proposing individual ambidexterity as a mechanism through which responsible leadership influences sustainable economic performance, sustainable social performance, and sustainable financial performance.
Our study proposes and tests a moderated mediation model. The objectives of our study are to assess: (a) thriving at work as a mediator between high-performance human resource practices (HPHRPs) and innovative behavior; (b) self-enhancement motive as a moderator between HPHRPs and thriving at work; and (c) self-enhancement motive as a moderator regarding the indirect positive effects of HPHRPs on innovative behavior via thriving at work. Data were collected from hotel managers and their frontline employees. The findings from partial least squares structural equation modeling reveal that thriving at work is a mediator between HPHRPs and innovative behavior, while self-enhancement motive strengthens the positive link between HPHRPs and thriving at work. Self-enhancement motive strengthens the indirect positive effects of HPHRPs on innovative behavior via thriving at work. Our study presents implications for managers and theoretical implications that focus on the test of unexplored moderating and moderated mediating effects mentioned above.
The genomic screening of hyper-thermophilic Pyrococcus abyssi showed uncharacterized novel α-amylase sequences. Homology modelling analysis revealed that the α-amylase from P. abyssi consists of an N-terminal GH57 catalytic domain, α-amylase central, and C-terminal domain. Current studies emphasize in-silico structural and functional analysis, recombinant expression, characterization, structural studies through CD spectroscopy, and ligand binding studies of the novel α-amylase from P. abyssi. The soluble expression of PaAFG was observed in the E. coli Rosetta™ (DE3) pLysS strain upon incubation overnight at 18 °C in an orbital shaker. The optimum temperature and pH of the PaAFG were observed at 90 °C in 50 mM phosphate buffer pH 6. The Km value for PaAFG against wheat starch was determined as 0.20 ± 0.053 mg while the corresponding Vmax value was 25.00 ± 0.67 μmol min-1 mg-1 in the presence of 2 mM CaCl2 and 12.5% glycerol. The temperature ramping experiments through CD spectroscopy reveal no significant change in the secondary structures and positive and negative ellipticities of the CD spectra showing the proper folding and optimal temperature of PaAFG protein. The RMSD and RMSF of the PaAFG enzyme determined through molecular dynamic simulation show the significant protein's stability and mobility. The soluble production, thermostability and broad substrate specificity make this enzyme a promising choice for various industrial applications.
Promoting entrepreneurial mindset and attitude among university students entails research exploring diverse factors that affect entrepreneurial intention, focusing on contextual factors. Contextual factors are crucial to entrepreneurship due to the interconnectedness between entrepreneurs and their environment. However, limited attention is given to understanding how context is addressed in supporting entrepreneurial competence development. Therefore, this study aims to address this gap by examining the role of contextual factors, perceived as both motivators and barriers to entrepreneurship, in shaping the attitudes, subjective norms, perceived behavioral control, and entrepreneurial intentions among university students in Malaysia. The study draws on the theory of planned behavior (TPB) to test hypotheses about the effect of perceived external context on entrepreneurial intention. Survey data from 317 students near graduation from entrepreneurship programs was analysed using PLS-SEM. Despite having solid attitudes towards becoming entrepreneurs and positive perceptions of their ability to become entrepreneurs (perceived behavioral control, PBC), participants’ negative perception of the external context for entrepreneurship dampened their intentions to engage in entrepreneurial activities. Perceptions of contextual barriers had a powerful effect on entrepreneurial intentions because PBC had a stronger effect on intentions than attitudes. This research outcome has practical implications for policymakers and educators in designing effective entrepreneurship education programs while advancing theoretical knowledge in entrepreneurial behavior and intention formation.
Alpha amylase belonging to starch hydrolyzing enzymes has significant contributions to different industrial processes. The enzyme production through recombinant DNA technology faces certain challenges related to their expression, solubility and purification, which can be overcome through fusion tags. This study explored the influence of SUMO, a protein tag reported to enhance the solubility and stability of target proteins when fused to the N -terminal of the catalytic domain of amylase from Pyrococcus abyssi (PaAD). The insoluble expression of PaAD in E. coli was overcome when the enzyme was expressed in a fusion state (S-PaAD) and culture was cultivated at 18 degrees C. Moreover, the activity of S-PaAD increased by 1.5 -fold as compared to that of PaAD. The ligand binding and enzyme activity assays against different substrates demonstrated that it was more active against 1 % glycogen and amylopectin. The analysis of the hydrolysates through HPLC demonstrated that the enzyme activity is mainly amylolytic, producing longer oligosaccharides as the major end product. The secondary structure analyses by temperature ramping in CD spectroscopy and MD simulation demonstrated the enzymes in the free, as well as fusion state, were stable at 90 degrees C. The soluble production, thermostability and broad substrate specificity make this enzyme a promising choice for various foods, feed, textiles, detergents, pharmaceuticals, and many industrial applications.
Multi-drug resistant (MDR) E. coli constitute a major public health burden globally, reaching the highest prevalence in the global south yet frequently flowing with travellers to other regions. However, our comprehension of the entire genetic diversity of E. coli colonising local populations remains limited. We quantified this diversity, its associated antimicrobial resistance (AMR), and assessed the impact of antibiotic use by recruiting 494 outpatients and 423 community dwellers in the Punjab province, Pakistan. Rectal swab and stool samples were cultured on CLED agar and DNA extracted from plate sweeps was sequenced en masse to capture both the genetic and AMR diversity of E. coli. We assembled 5,247 E. coli genomes from 1,411 samples, displaying marked genetic diversity in gut colonisation. Compared with high income countries, the Punjabi population generally showed a markedly different distribution of genetic lineages and AMR determinants, while use of antibiotics elevated the prevalence of well-known globally circulating MDR clinical strains. These findings implicate that longitudinal multi-regional genomics-based surveillance of both colonisation and infections is a prerequisite for developing mechanistic understanding of the interplay between ecology and evolution in the maintenance and dissemination of (MDR) E. coli.
In the dynamic landscape of rapid change and the pervasive influence of the digital revolution, the discussion surrounding the impact of digital transformation on the innovation performance of firms has become a focal point of intense debate. This paper aims to contribute to the evolution and advancement of traditional organizations toward high-quality development by addressing this issue through the integration of technology into the framework, leveraging the resource-based theory. The study seeks to explore the influence of digital transformation on innovation performance, specifically examining the role of supplier concentration in this relationship. Additionally, we investigate the moderating effect of CEO financial experience on the association between digital transformation and innovation performance. Utilizing multiple regression methodologies and analyzing data from Chinese listed firms spanning the period from 2007 to 2022, our empirical findings reveal a direct positive relationship between digital transformation and innovation performance. Furthermore, the study uncovers an indirect pathway through which digital transformation enhances innovation performance by mitigating supplier concentration. Notably, the positive impact of digital transformation is amplified by a CEO's background in finance. Finally, the effect of digital transformation on innovation performance is particularly pronounced in sectors such as state-owned entities, advanced technology companies, large-scale businesses, and those in their maturity phase. These insights provide valuable contributions to addressing concerns related to digital transformation, particularly in emerging economies like China. The findings offer essential lessons for navigating the transition to Industry 4.0 and fostering sustainable innovative practices. By emphasizing the role of supplier concentration and the moderating influence of CEO financial experience, this research contributes to a nuanced understanding of how digital transformation can positively impact innovation performance across diverse sectors.