bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of activity cliffs in structure-activity landscape of androgen receptor binding chemicals
Authors: Vivek-Ananth R.P. , Sahoo Ajaya Kumar , Baskaran Shanmuga Priya , Ravichandran Janani , Samal Areejit 
Published: December 2022

AbstractAndrogen mimicking environmental chemicals can bind to Androgen receptor (AR) and can cause severe effects on the reproductive health of males. Predicting such endocrine disrupting chemicals (EDCs) in the human exposome is vital for improving current chemical regulations. To this end, QSAR models have been developed to predict androgen binders. However, a continuous structure-activity relationship (SAR) wherein chemicals with similar structure have similar activity does not always hold. Activity landscape analysis can help map the structure-activity landscape and identify unique features such as activity cliffs. Here we performed a systematic investigation of the chemical diversity along with the global and local structure-activity landscape of a curated list of 144 AR binding chemicals. Specifically, we clustered the AR binding chemicals and visualized the associated chemical space. Thereafter, consensus diversity plot was used to assess the global diversity of the chemical space. Subsequently, the structure-activity landscape was investigated using SAS maps which capture the activity difference and structural similarity among the AR binders. This analysis led to a subset of 41 AR binding chemicals forming 86 activity cliffs, of which 14 are activity cliff generators. Additionally, SALI scores were computed for all pairs of AR binding chemicals and the SALI heatmap was also used to evaluate the activity cliffs identified using SAS map. Finally, we provide a classification of the 86 activity cliffs into six categories using structural information of chemicals at different levels. Overall, this investigation reveals the heterogeneous nature of the structure-activity landscape of AR binding chemicals and provides insights which will be crucial in preventing false prediction of chemicals as androgen binders and developing predictive computational toxicity models in the future.
Salivary Glands treated with AAV vectors encoding PYY and exendin-4 impact upon taste perception and body mass accumulation in mice
Authors: Iyer S. , Montmayeur JP , Zolotukhin S. , Dotson C.D. 
Published: December 2022

ABSTRACTThe availability of high-calorie foods is likely a causative factor for high rates of obesity and metabolic disorders, which have been linked to food intake dysregulation. Several gut peptides have been implicated in feeding modulation and body mass accumulation. For example, glucagon peptide-like 1 (GLP-1) and peptide tyrosinetyrosine (PYY) have been shown to mediate satiety and reduce food intake. While systemic administration of such peptides has been explored as a therapy for metabolic disease, the effects of these hormones on taste signaling should also be considered given the importance of taste to feeding decisions. Peptide signaling systems are present in taste buds and oral GLP-1 and PYY signaling has been shown to influence taste responsiveness and feeding. Indeed, we previously demonstrated that genetic knockout of PYY in mice can impact on taste responsiveness and feeding and that viral overexpression of PYY in the salivary glands of these mice can rescue responsiveness. The present work uses AAV-mediated salivary gland treatment of both GLP-1 receptor agonist exendin-4 and PYY encoding vectors to explore the impact of the presence of these peptides on taste and body-mass accumulation in wild-type mice with intact peptide signaling systems. Results showed a significant effect of salivary gland treatment on responsiveness to multiple taste qualities. Treatment with a vector designed to overexpress both peptides in saliva resulted in substantial reduction in body mass accumulation. These findings show taste modulation and impacts on body mass accumulation by the targeting of salivary glands with vectors designed to overexpress metabolic peptides in wild-type mice and suggest that the taste bud is a promising substrate for food intake modulation.
Structural Model for Self-Limiting β-strand Arrangement Within an Alzheimer’s Amyloid-β Oligomer
Authors: Gao Yuan , Prasad Ramesh , Randolph Peter S. , Watzlawik Jens O. , Robang Alicia S. , Guo Cong , Stagg Scott M. , Zhou Huan-Xiang , Rosenberry Terrone L. , Paravastu Anant K. 
Published: December 2022

AbstractPrevious reports revealed that sodium dodecyl sulfate near its critical micelle concentration can drive the assembly of Aβ42 along an oligomeric pathway. This pathway produces a 150 kDa peptide oligomer (approximately 32 peptide molecules or protomers) that does not aggregate further into amyloid fibrils. Solid-state nuclear magnetic resonance (NMR) spectroscopy revealed structural features distinguishing the 150 kDa oligomer from fibrils. A puzzling feature was the coexistence of parallel and antiparallel β-sheets within the oligomer structure. Here we present new atomic-level structural constraints obtained via solid-state NMR spectroscopy, benefitting from improved resolution via sample concentration by ultracentrifugation. In addition, two-dimensional cryo-electron microscopy (cryo-EM) reconstruction revealed a 4-fold symmetric shape. We propose a structural model to rationalize the solid-sate NMR- and cryo-EM-derived structural constraints. This model has a hollow square cylinder shape, with antiparallel β-sheets formed by residues 33-39 lining the inner walls and parallel β-sheets formed by residues 11-22 lining the outer walls. Within successive layers, the outer β-strands on each side of the square cylinder alternate between two forms: one within a U-shaped protomer and another within L-shaped protomer. Molecular dynamics simulations show that, when the oligomer model is embedded in a lipid membrane, ions permeate through the central pore, with cation selectivity. The model further motivates an assembly pathway-based interpretation that may explain why the 150 kDa oligomer does not undergo further aggregation into amyloid fibrils.Significance StatementAβ oligomers are thought to be the most toxic species in Alzheimer’s disease. Their sizes range from 2 to ∼50 protomers. Most published experimental data on Aβ oligomers indicate that they, like fibrils, are composed of β-sheets, but it is a mystery why any β-sheet aggregate would exist as a stable oligomer without undergoing further aggregation into fibrils. Here, structural constraints from solid-state NMR and cryo-EM led us to an oligomer model with a hollow square cylinder shape capable of conducting ions when embedded in a lipid membrane. Based on the model, we argue that geometric frustration may distinguish the assembly pathway that produces this oligomer from fibril-forming assembly pathways.
Distinct neurofunctional alterations during motivational and hedonic processing of natural and monetary rewards in depression – a neuroimaging meta-analysis
Authors: Bore Mercy Chepngetich , Liu Xiqin , Gan Xianyang , Wang Lan , Xu Ting , Ferraro Stefania , Li Liyuan , Zhou Bo , Zhang Jie , Vatansever Deniz , Biswal Bharat , Klugah-Brown Benjamin , Becker Benjamin 
Published: December 2022

AbstractReward processing dysfunctions are considered a candidate mechanism underlying anhedonia and apathy in depression. Neuroimaging studies have documented that neurofunctional alterations in mesocorticolimbic circuits may neurally mediate these dysfunctions. However, common and distinct neurofunctional alterations during motivational and hedonic evaluation of monetary (extrinsic) and natural (intrinsic) rewards in depression have not been systematically examined. Here, we capitalized on pre-registered neuroimaging meta-analyses to (1) establish general reward-related neural alterations in depression, (2) determine common and distinct alterations during the receipt and anticipation of monetary versus natural rewards, and, (3) characterize the differences on the behavioral, network and molecular level. The pre-registered meta-analysis (https://osf.io/ay3r9) included 633 depressed patients and 644 healthy controls and revealed generally decreased subgenual anterior cingulate cortex and striatal reactivity towards rewards in depression. Subsequent comparative analysis indicated that monetary rewards led to decreased hedonic reactivity in the right ventral caudate while natural rewards led to decreased reactivity in the bilateral putamen. These regions exhibited distinguishable profiles on the behavioral, network and molecular level. Further analyses demonstrated that the right thalamus and left putamen showed decreased activation during the anticipation of monetary reward. The present results indicate that distinguishable neurofunctional alterations may neurally mediate reward-processing alterations in depression, in particular, with respect to monetary and natural rewards. Given that natural rewards prevail in everyday life, our findings suggest that reward-type specific interventions are warranted and challenge the generalizability of experimental tasks employing monetary incentives to capture reward dysregulations in everyday life.
The impact of destination online review content characteristics on travel intention: experiments based on psychological distance perspectives
Authors: Zhu Zhangxiang , Zhao Yaxin , Wang Jing 
Published: December 2022

PurposeThis study aims to explore the relationship between the content characteristics of destination online reviews and travel intention under three individual circumstances: temporal distance, social distance and experiential distance.Design/methodology/approachBased on construal-level theory (CLT), this study divides online travel reviews into concrete and abstract reviews. Three experiments were conducted to test the moderating effects of temporal distance, social distance and experiential distance on the influence of review content characteristics on tourists' travel intentions.FindingsThe results show that abstract reviews would lead to higher travel intentions than concrete reviews. Furthermore, tourists' travel intentions differed depending on social distance and were significantly affected by reviews posted by reviewers similar to review recipients. In addition, the study contributes by discovering that the moderating effects of temporal distance, social distance and experiential distance were not significant, which differs from most of the previous research conclusions.Originality/valueThis study focused on review content characteristics, which provided a novel perspective for constructing online travel reviews. Furthermore, this research defined the concept of experiential distance in the context of online travel and expanded the research on psychological distance.
Understanding the role of entrepreneurial orientation in creating ambidextrous competitive advantage: a comparative-design, longitudinal study
Authors: Chen Yen-Chun , Arnold Todd , Liu Ping-Yu , Huang Chun-Yao 
Published: December 2022

Purpose
This research aims to investigate how entrepreneurial orientation influences a firm’s differentiation–cost advantage ambidexterity (DCAA) and performance indirectly through dynamic capabilities, while also investigating the impact of the interactive effect of the level and consistency of entrepreneurial orientation on dynamic capabilities. The goal of this study is to better understand the importance of consistently following an entrepreneurial orientation, as well as the linkage of such a consistently implemented strategy upon gaining both a cost and differentiation positioning enhancement.

Design/methodology/approach
Two empirical studies are conducted to test the proposed hypotheses – one longitudinal with multiple forms of data (i.e. text data, survey data and archival data) from 100 Taiwanese electronics firms and the other using primary data from a survey of senior managers.

Findings
Entrepreneurial orientation improves dynamic capabilities, which in turn promote superior DCAA and enhanced firm performance. In addition, as captured through a unique measure of consistency allowed through computer-aided text analysis, the results indicate that the effect of entrepreneurial orientation on dynamic capabilities is amplified when a firm consistently adopts entrepreneurial decisions and actions.

Research limitations/implications
The specific context was a sample of electronics firms in Taiwan. This limits the generalization of findings, as would be possible with assessing the hypotheses in other industries.

Practical implications
This research clearly demonstrates the significance of consistency in pursuing a strategic orientation. The consistent support and deployment of resources facilitates an organization’s achieving positive outcomes associated with an entrepreneurial orientation.

Originality/value
While entrepreneurial orientation contributes to firm performance, extant knowledge on the internal process through which entrepreneurial orientation affects performance is relatively limited. The findings not only highlight the full mediating role of dynamic capabilities and DCAA, but also shed light on the importance of consistency in entrepreneurial orientation over time.
Co-produced or co-opted? Reflections on the “movement” to promote good employment in Greater Manchester
Authors: Johnson Mathew , Herman Eva , Hughes Ceri 
Published: December 2022

PurposeThe purpose of this paper is to explore the development of the Greater Manchester Good Employment Charter – a top-down soft regulation initiative that has been framed as a “movement” to promote good employment across the local area.Design/methodology/approachThe research draws on 24 semi-structured interviews with policy officers, trade unions, employers and civil society actors and various professional and employer bodies who have been involved in the charter since its inception. The interview data are complemented by documentary analysis.FindingsThe findings underline the importance of institutional factors such as political access points and the mobilising structures of the state in creating a space for progressive employment policies such as charters to emerge. We also find that the framing of the charter as a mechanism to achieve both social justice and improved productivity allows diverse actors to engage, but at the same time this results in a degree of ambiguity over the normative and substantive reference points for “good employment”.Originality/valueThe article contributes to our understanding of the changing nature of top-down political initiatives that seek to change business practices by engaging a wide range of stakeholders as Allies not adversaries. We argue that while charters are a potentially useful demand side intervention, in the absence of significant workplace or grassroots engagement and without coordinated mechanisms of monitoring and enforcement, their effects on low wage labour markets will be limited.
Work changes and employee perceptions of co-worker flexible work policy use: a moderated mediation study
Authors: Davis Svetlana , Murphy Sara A. , Watkins Joanna 
Published: December 2022

PurposeThe present research aims to understand how and why flexible work arrangement (FWA) policy use by co-workers affects policy non-users by investigating perceived changes to work, fairness and organizational identification as factors that shape policy non-users’ job satisfaction.Design/methodology/approachA survey was distributed to 300 Canadian respondents solicited from an online panel owned by Qualtrics Inc. Hypotheses were developed and tested using a moderating mediation model. SPSS Macro Process (Hayes) was used to test the hypotheses.FindingsThis survey found that perceiving negative changes to work stemming from co-worker FWA use corresponded to policy non-user job satisfaction, fairness dimensions mediated this effect and organizational identification moderated the relationship driven by interactional fairness. Policy non-users who care most about organizations seem to be most vulnerable to the negative consequences associated with co-worker FWA policy use.Originality/valueFWA use has been linked to many positive outcomes for policy users. However, the workplace adjustments that occur to accommodate policy use by co-workers could also have implications for policy non-users. This study explores the effects of FWA policy use by co-workers on policy non-users job satisfaction.
CO2 emissions policy thresholds for renewable energy consumption on economic growth in OPEC member countries
Authors: Abdulqadir Idris Abdullahi 
Published: December 2022

Purpose
This study aims to examine the nexuses between economic growth, trade openness, renewable energy consumption and environmental degradation among organization of petroleum exporting countries (OPEC) members over the period 1990–2019.

Design/methodology/approach
The empirical strategy for the study includes dynamic heterogeneous panel pooled mean group (PMG), mean group (MG) estimators and dynamic panel threshold regression (TR) analysis. For clarity, PMG and MG are used to explore the long-run relationship between the variables, whereas TR is used to uncover the actionable and complementary policy thresholds in the nexuses between green growth and environmental degradation.

Findings
The empirical evidence is based on the significant estimates from PMG and TR. First, using PMG, the study finding revealed a long-run relationship between economic growth and environmental degradation via the PMG estimator. Second, using TR, the study revealed an actionable threshold for carbon dioxide emissions (CO2) metrics tons per capita (mtpc) not beyond a critical mass of 4.88mtpc, and the complementary policy threshold of 85% of the share of trade to gross domestic product, respectively.

Research limitations/implications
The policy relevance of the thresholds is apparent to policymakers in the cartel and for policy formulation. The policy implication of this study is straightforward.

Originality/value
The novelty of this study stalk in the extant literature on providing policymakers with an actionable threshold for CO2 emissions with the corresponding complementary threshold for trade policies in the nexuses between green growth and the environment.
The readiness of manufacturing industries to transit to Quality 4.0
Authors: Maganga Deusdedith Pastory , Taifa Ismail W.R. 
Published: December 2022

PurposeThis research provides the essential aspects of the transition from traditional quality methods like total quality management, quality assurance and quality control to a new quality approach linked with the Industry 4.0 era. The purpose of this paper is to address this issue.Design/methodology/approachThe study used a survey method to obtain the practitioners' perceptions of the Quality 4.0 (Q4.0) concepts. Both closed-ended and open-ended structured questionnaires assessed the perceptions of respondents regarding manufacturers' readiness and Q4.0 awareness to transition to Q4.0. Non-probability and purposive sampling tactics selected 15 Tanzanian manufacturing industries (TMIs). Garnered data were scrutinised quantitatively and qualitatively utilising Minitab® 20, SmartPLS 3.3.7 and MAXQADA 2020 software packages.FindingsThe results indicate that TMIs are equipped to deploy the Q4.0 approach because industrialists are familiar with the concept's characteristics and dimensions and the benefits of implementing Q4.0. Most TMIs utilise a Q3.0 method for managing quality, while some manufacturing industries have begun to apply Q4.0 leveraging technologies. The study revealed several factors influencing Q4.0 readiness in TMIs, including leveraged technology adoption, training, Q4.0 skills, infrastructures, the government set-up, top management support, Q4.0 strategy and vision, collaboration, awareness, knowledge of Q4.0, customer and supplier centeredness and organisational culture.Research limitations/implicationsThe implication of this study is on Q4.0 awareness creation so that industries can grab the advantages of Q4.0 leveraged technologies. Another implication is that organisational readiness factors identified in this study are critical for the effective adoption of Q4.0. The highlighted influences may be utilised as indications to determine an organisation's readiness to transition to the Q4.0 approach. This research was limited to TMIs, excluding service firms, mining, and the building and construction industry due to differences in their mode of operation.Originality/valueDetermining readiness factors and awareness for the Q4.0 study is probably the first amongst the seven East African countries, including Tanzania. This study thus bridges a huge gap in fulfilling the need of this research type.
Climate change education in China: a pioneering case of its implementation in tertiary education and its effects on students’ beliefs and attitudes
Authors: Tang Kuok Ho Daniel 
Published: December 2022

Purpose
In view of a lack of evidence on the effectiveness of climate change education (CCE) in China, this study aims to evaluate if a CCE course newly designed based on research recommendations and implemented with established pedagogy was effective in changing the beliefs and attitudes of first-year science students.

Design/methodology/approach
This study took a simple longitudinal approach with surveys administered at the beginning and the end of the course and the differences in the responses analyzed with nonparametric statistical analyses.

Findings
The results showed that the course produced significant changes in the beliefs concerning the anthropogenic causes of climate change and vulnerability to its impacts, which results in inequality of the impacts received. However, the course did not produce significant attitudinal changes among the students. Spearman’s correlation, which affirmed the belief–attitude association, revealed that the students already had desirable attitudes toward climate change and these attitudes had not been reinforced. The students’ perception of the importance of local government in climate action increased by the end of the course. Multimedia-aid learning, debates and discussions were useful in conveying the concepts of responsibility, ethics and vulnerability, but the addition of student-led community projects will increase personal significance of the course.

Research limitations/implications
This study is instrumental for the development of a regional model of CCE in the mainstreaming of education for sustainable development in China, knowing that the regional approach is crucial to address the nuances in climate change knowledge, hence conceptions and beliefs across regions and, even, between different sectors of a region. This regional experience could also serve as a reference for other similar settings, particularly those of the developing countries.

Originality/value
This study presents one of the very few studies dedicated to gauging the effects of CCE in China, particularly of a newly developed climate change course, on the beliefs and attitudes of students. This permits pedagogical development and continuous improvement of CCE in China.