bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATP energy-independently modulates the folding equilibrium of ALS-causing C71G-hPFN1
Authors: Kang Jian , Lim Liangzhong , Song Jianxing 
Published: August 2023

AbstractC71G is the most aggregation-prone and toxic mutant of 140-residue human profin-1 (hPFN1) that causes familial ALS by gain of toxicity, but its underlying mechanisms still remain unknown. C71G-hPFN1 exists in an equilibrium between folded and unfolded states, whose dynamic/thermodynamic properties and modulation are not yet defined. Here, we utilized NMR to quantify the populations to be 55.2% and 44.8% respectively for folded and unfolded states exchanging at 11.7 Hz. Intriguingly, even the folded state of C71G-hPFN1 has increased ps-ns flexibility and reduced thermodynamic stability, thus rationalizing its high aggregation-proneness. Strikingly, C71G-hPFN1 provides a unique model to unambiguously visualize the effects of ATP and 11 related molecules on its folding equilibrium by NMR. Unexpectedly, ATP completely converted C71G-hPFN1 into the folded state at 1:2, which is physiologically relevant in most living cells. By contrast, TMAO, a well-known protein-folding inducer, showed no detectable conversion even at 1:2000. Surprisingly, the inducing capacity of ATP comes from its triphosphate group, but free triphosphate strongly triggered aggregation. The inducing capacity was determined to rank as: ATP = ATPP = PPP > ADP = AMP-PNP = AMP-PCP = PP, while AMP, Adenosine, P and NaCl showed no detectable capacity. Mechanistically, ATP and triphosphate appear to enhance the intrinsic folding capacity encoded by the sequence. Therefore, by joining Adenosine and triphosphate ATP appears to integrate three abilities: inducing folding, inhibiting aggregation and increasing stability. Our study provide a mechanism for the finding that some single-cell organisms still use polyphosphates as primordial chaperones. Moreover, ATP continue to play foundational roles in modern cells, shedding light on the longstanding enigma of the age-related onset of FALS, which coincides with the ageing-dependent reductions in ATP concentrations.
Observing Mechanosensitive Channels in Action in Living Bacteria
Authors: Sharifian Gh. Mohammad , Wilhelm Michael J. , Dai Hai-Lung 
Published: August 2023

ABSTRACTMechanosensitive (MS) channels act to protect the cytoplasmic membrane (CM) of living cells from environmental changes in osmolarity. In this report, we demonstrate the use of time-resolved second-harmonic light scattering (SHS) as a means of experimentally observing the relative state (open vs. closed) of MS channels in living bacteria suspended in different buffer solutions. Specifically, the state of the MS channels was selectively controlled by changing the composition of the suspension medium, inducing either a transient or persistent osmotic shock. SHS was then used to monitor transport of the SHG-active cation, malachite green (MG) across the bacterial CM. When MS channels were forced open, MG cations were able to cross the CM at a rate at least two orders of magnitude faster compared to when the MS channels were closed. These observations were corroborated using both numerical model simulations and complementary fluorescence experiments, in which the propensity for the CM impermeant cation, propidium to stain cells was shown to be contingent upon the relative state of the MS channels (i.e., cells with open MS channels fluoresced red, cells with closed MS channels did not). Application of time-resolved SHS to experimentally distinguish MS channels opened via osmotic shock vs. chemical activation, as well as a general comparison to the patch-clamp method is discussed.
Overexpression and nonsynonymous mutations of UDP-glycosyltransferases potentially associated with pyrethroid resistance inAnopheles funestus
Authors: Al-Yazeedi Talal , Muhammad Abdullahi , Irving Helen , Ahn Seung-Joon , Hearn Jack , Wondji Charles S. 
Published: August 2023

AbstractUDP-glycosyltransferases (UGTs) constitute a superfamily of enzymes that play a vital role in the biotransformation of diverse hydrophobic substrates into more hydrophilic products, thereby facilitating their excretion from the cell through transporters. The significance of UGTs in conferring insecticide resistance has been emphasized in various insect species. In this study, we characterisedAnopheles funestusUGT genes genome-wide and explored their evolution and association with pyrethroid resistance. We combined genome-wide association of pooled-template sequencing (GWAS-PoolSeq) with the transcriptomic profile of pyrethroid-resistantAn. funestuspopulations, and deep targeted sequencing of UGTs from 80 individual mosquitoes collected in Malawi, Uganda, Cameroon and the two laboratory colonies (FANG and FUMOZ) to investigate the role of UGTs in pyrethroid resistance. We identified common overexpression of UGT310B2 (AFUN000679) in the resistant laboratory colony (FUMOZ) and resistant field populations from Malawi, Cameroon and Uganda. Significant gene-wiseFstdifferentiation between the resistant and putatively susceptible populations was observed for UGT301C2 and UGT302A3 in Malawi, as well as UGT306C2 in Uganda. Furthermore, the gene-wise Tajimas D density curves of the sequenced regions provided insights into genome-wide processes elucidating population structures withinAn. funestuspopulations from these three countries, supporting previous observations. Additionally, we identified significantly differentiated nonsynonymous mutations within UGT genes, which may potentially contribute to pyrethroid resistance. The identified role ofAn. funestusUGT genes in pyrethroid resistance has direct implications for current vector control strategies, management approaches, and the prediction of potential cross-resistance to other insecticides that can be directly detoxified by UGTs.
Digital transformation in family-owned winery SMEs: an exploratory analysis in the South-Italian context
Authors: Costa Alessandra , Presenza Angelo , Abbate Tindara 
Published: August 2023

PurposeThis work aims to offer a better understanding of the inevitable challenges related to the digital transformation in the family-owned low-tech SMEs, examining the role assumed by familiness in this specific context. To this end, it examines the main factors that influence the adoption and implementation of digital technologies in the family-owned low-tech SMEs.Design/methodology/approachThe study uses a multiple case studies approach, by investigating the case of family-owned low-tech SMEs operating in the winery sector and located in the South-Italy area.FindingsBased on the empirical evidence, findings show how familiness influence the digital transformation of family-owned SMEs and highlight three main factors – individual, process and organization – relevant for the introduction and use of digital technologies in the productive and innovative activities of these organizations.Originality/valueThis paper fills the research gap existing in the literature on the family business. Firstly, it focuses on the digital transformation phenomenon and underlines how familiness, within family-owned low-tech SMEs, can differently influence the firm's innovation processes primarly based on the use of digital technologies oriented to enable business improvements. Then, it identifies diverse dimensions that can act as “barriers” or “facilitators” for adopting advanced digital technologies within the organizations here examined.
Investigating the impact of food tourism vlogger entrepreneurs' language characteristics on audiences' attitude and behaviours
Authors: Hutchinson Wei , Djafarova Elmira , Liu Shaofeng , Abdelrahman Mahmoud 
Published: August 2023

PurposeDespite entrepreneurial linguistic style gaining increased attention in entrepreneurship studies, the field for digital vlogger entrepreneurs still lacks a comprehensive understanding of how linguistic patterns enhance audiences attitude and behaviour. This study aims to propose a conceptual model of “language-mental imagery-attitude-behaviour model” that leads to the examination of rich sensory language style of food travel vlogger entrepreneurs and its persuasive effect on audiences' attitude and behavioural intention.Design/methodology/approachThe present study utilises a stimulus-based survey method that involves a sensory-rich vlog script extracted from a high social media engagement authentic vlog. Data are collected through an online questionnaire distributed to a sample of 355 participants via the Amazon Turk mechanism. The study employs confirmatory factor analysis and structural equation modelling to test the proposed hypotheses, with the aim of contributing to the advancement of theories of embodied cognition in entrepreneurial language by examining the attitudes and behaviours of audiences exposed to sensory-rich language. The findings of this research provide valuable insights into the effects of sensory-rich language on audience responses and can inform future research on the role of embodied cognition in entrepreneurial communication.FindingsThe findings demonstrate that vlogger entrepreneurial sensory-rich linguistic communication style positively influence audiences' attitude, behavioural involvement with food and intention to taste. Visit intention will be enhanced via the mediating effects of attitude, behavioural involvement with food and intention to taste.Practical implicationsThis research highlights the significance of sensory-rich language for vlogger entrepreneurs in entrepreneurial communication, digital storytelling and for destination marketing enterprises in creating a digital sensory engagement marketing strategy.Originality/valueThe study contributes to the literature by elucidating the theories of embodied cognition in entrepreneurial communication. By examining the relationships between vlogger communication evoked mental imagery, audiences attitude and behaviours, this study provides novel insights into the effectiveness of sensory-rich language in vlogger entrepreneurial communication and its impact on audience engagement. These findings have important implications for communication scholars and practitioners alike, shedding light on the role of embodied cognition in entrepreneurial language and the potential of sensory-rich language to enhance audience engagement.
Vulnerability and resilience among women migrant street vendors during the COVID-19 pandemic
Authors: Thanh Pham Tien , Bao Duong Pham 
Published: August 2023

Purpose
Women migrant street vendors are considered a vulnerable group in societies, thereby being hard hit during a crisis. This research aims to examine effects of COVID-19 social distancing on their businesses, consumption, health and general lives; solutions and mitigation strategies that they adopted in response to these adverse effects; and their recovery of socioeconomic lives after social distancing.

Design/methodology/approach
The data were collected from the women migrant street vendors in urban Vietnam. Descriptive statistics, probit model and ordered probit model were used for empirical analysis.

Findings
Women migrant street vendors faced immense challenges during social distancing. They also lacked solutions to sustain their businesses and were forced to resort to various mitigation strategies. Their socioeconomic lives were also slow to recover after social distancing. In addition, those experiencing greater business loss faced more adverse effects during social distancing and have more difficulties in the recovery of socioeconomic lives after social distancing.

Practical implications
This research highlights the importance of redesigning social policies to support women migrant street vendors during crises. It also emphasizes the need to formalize and legalize their activities to foster sustainable and inclusive development in the long term.

Originality/value
To the best of the authors’ knowledge, this research is among the first attempts to explore the effects of COVID-19 social distancing on the women migrant street vendors and to examine how they respond to these adverse effects.
Receptiveness of mass-engineered timber (MET) residential buildings among young stakeholders
Authors: Shang Gao , Pheng Low Sui , Fai Benjamin Peh Kah 
Published: August 2023

PurposeTraditional construction materials and methodologies are often perceived to be unproductive, labour-intensive and detrimental to the environment. Mass-engineered timber (MET) is a new structural material that is capable of overcoming numerous issues that otherwise affect the built environment. This study was formulated to assess the current attitude and perception of young Singaporeans towards the concept of Engineered Timber Residential Buildings (ETRBs).Design/methodology/approachThe study employs the mixed-method approach. Questionnaires were used as the primary mode of data gathering. These were disseminated to Singaporeans between the age of 18 and 35 years. A total of 179 valid responses were gathered. Semi-structured interviews were subsequently conducted with six individuals with different demographics in order to gain further insightful opinions and to allow cross validation of responses.FindingsStatistical analysis revealed that 80% of respondents were willing to accept ETRBs, but a lack of awareness and knowledge of MET and the presence of misconceptions, such as an association with deforestation, may present concerns. The study also revealed that individual acceptance of ETRBs is not affected by demographics.Originality/valueThe production of MET involves lower overall carbon emissions than that of conventional materials, and this also allows adoption of the Design for Manufacturing and Assembly (DfMA) concept and offers the benefit of carbon sequestration. Residential buildings are the second most common building type in Singapore; significant benefits can be gained if MET is used as the primary material for residential buildings. In general, young stakeholders in Singapore welcome the concept of ETRBs, despite possessing uncertainties about ETRBs—understandable given that the material lacks a track record of usage. Public authorities are thus advised to explore the feasibility of materialising the concept of ETRBs as an option for public housing.
Is it time to reboot welfare economics? Overview
Authors: Coyle Diane , Fabian Mark , Beinhocker Eric , Besley Tim , Stevens Margaret 
Published: August 2023

AbstractThe contributions of economists have long included both positive explanations of how economic systems work and normative recommendations for how they could and should work better. In recent decades, economics has taken a strong empirical turn as well as having a greater appreciation of the importance of the complexities of real‐world human behaviour, institutions, the strengths and failures of markets, and interlinkages with other systems, including politics, technology, culture and the environment. This shift has also brought greater relevance and pragmatism to normative economics. While this shift towards evidence and pragmatism has been welcome, it does not in itself answer the core question of what exactly constitutes ‘better’, and for whom, and how to manage inevitable conflicts and trade‐offs in society. These have long been the core concerns of welfare economics. Yet, in the 1980s and 1990s, debates on welfare economics seemed to have become marginalised. The articles in this Fiscal Studies symposium engage with the question of how to revive normative questions as a central issue in economic scholarship.
Sex‐ and APOE‐specific genetic risk factors for late‐onset Alzheimer's disease: Evidence from gene–gene interaction of longevity‐related loci
Authors: Dato Serena , De Rango Francesco , Crocco Paolina , Pallotti Stefano , Belloy Michael E. , Le Guen Yann , Greicius Michael D. , Passarino Giuseppe , Rose Giuseppina , Napolioni Valerio 
Published: August 2023

AbstractAdvanced age is the largest risk factor for late‐onset Alzheimer's disease (LOAD), a disease in which susceptibility correlates to almost all hallmarks of aging. Shared genetic signatures between LOAD and longevity were frequently hypothesized, likely characterized by distinctive epistatic and pleiotropic interactions. Here, we applied a multidimensional reduction approach to detect gene–gene interactions affecting LOAD in a large dataset of genomic variants harbored by genes in the insulin/IGF1 signaling, DNA repair, and oxidative stress pathways, previously investigated in human longevity. The dataset was generated from a collection of publicly available Genome Wide Association Studies, comprising a total of 2,469 gene variants genotyped in 20,766 subjects of Northwestern European ancestry (11,038 LOAD cases and 9,728 controls). The stratified analysis according to APOE*4 status and sex corroborated evidence that pathways leading to longevity also contribute to LOAD. Among the significantly interacting genes, PTPN1, TXNRD1, and IGF1R were already found enriched in gene–gene interactions affecting survival to old age. Furthermore, interacting variants associated with LOAD in a sex‐ and APOE‐specific way. Indeed, while in APOE*4 female carriers we found several inter‐pathway interactions, no significant epistasis was found in APOE*4 negative females; conversely, in males, significant intra‐ and inter‐pathways epistasis emerged according to APOE*4 status. These findings suggest that interactions of risk factors may drive different trajectories of cognitive aging. Beyond helping to disentangle the genetic architecture of LOAD, such knowledge may improve precision in predicting the risk of dementia and enable effective sex‐ and APOE‐stratified preventive and therapeutic interventions for LOAD.
Pharmaceutical management of type 2 diabetes among Indigenous Australians living in urban or rural locations: a comparative study using a national general practice database
Authors: Pink Natalie , Liddell Antoinette , Gonzalez‐Chica David , Stocks Nigel 
Published: August 2023

AbstractIntroductionType 2 diabetes is more prevalent among Aboriginal and Torres Strait Islander Peoples, especially those living in rural than urban areas. However, little is known about how diabetes is managed in different settings.ObjectiveTo investigate differences in the prevalence of diabetes and the prescription of antidiabetic medications for Aboriginal and/or Torres Strait Islander Peoples living in urban or rural Australia.DesignCross‐sectional study using de‐identified electronic medical records of 29,429 Aboriginal and/or Torres Strait Islander adults (60.4% females; mean age 45.2 ± 17.3 years) regularly attending 528 ‘mainstream’ Australian general practices (MedicineInsight) in 2018.FindingsThe prevalence of diabetes was 16.0%, and it was more frequent among those living in rural areas (22.0; 95% CI 19.3–24.4) than inner regional (17.6%; 95% CI 16.0–19.2) or major cities (15.8%; 95% CI 14.7–17.0; p < 0.001). The highest prevalence of diabetes was for males living in rural settings (25.0%). Of those with diabetes, 71.6% (95% CI 69.0–74.0) were prescribed antidiabetics, with a similar frequency in urban and rural areas (p = 0.291). After adjustment for sociodemographics, the only difference in diabetes management was a higher prescription of sulfonylureas in rural areas than in major cities (OR 1.39; 1.07–1.80).DiscussionThe prevalence of diabetes was similar to other national data, although we found it was more frequent amongst Aboriginal and/or Torres Strait Islander males, especially those from rural areas.ConclusionDespite current recommendations, one‐in‐four Indigenous Australians with diabetes were not prescribed antidiabetics. The clinical significance of more frequent prescriptions of sulfonylureas in rural locations remains unclear.
Compound heterozygous variants in RAB34 in a rare skeletal ciliopathy syndrome
Authors: Batkovskyte Dominyka , Komatsu Maya , Hammarsjö Anna , Pooh Ritsuko , Shimokawa Osamu , Ikegawa Shiro , Grigelioniene Giedre , Nishimura Gen , Yamada Takahiro 
Published: August 2023

AbstractSkeletal ciliopathies are a heterogenous group of congenital disorders characterized by multiple internal abnormalities, and distinct radiographic presentation. Pathogenic variants in at least 30 cilia genes are known to cause skeletal ciliopathies. Here we report a fetus with an atypical skeletal ciliopathy phenotype and compound heterozygous variants in the RAB34 gene. The affected fetus had multiple malformations, including posterior neck edema, micrognathia, low‐set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre‐ and postaxial polydactyly. Genome sequencing identified compound heterozygous variants in the RAB34 gene: maternal c.254T>C, p.(Ile85Thr), and paternal c.691C>T, p.(Arg231*) variants. Only the paternal variant was present in the unaffected sibling. Evidence in the literature indicated that Rab34−/− mice displayed a ciliopathy phenotype with cleft palate and polydactyly. These features were consistent with malformations detected in our patient supporting the pathogenicity of the identified RAB34 variants. Overall, this case report further expands genetic landscape of human ciliopathy syndromes and suggests RAB34 as a candidate gene for skeletal ciliopathies.
Sarcopenia assessed by computed tomography or magnetic resonance imaging is associated with the loss of response to biologic therapies in adult patients with Crohn's disease
Authors: Liu Jingjing , Tang Hongye , Lin Tingting , Wang Jiangchuan , Cui Wenjing , Xie Chao , Wang Zhongqiu , Chen Yugen , Chen Xiao 
Published: August 2023

AbstractSarcopenia occurs in patients with Crohn's disease (CD). However, the association between sarcopenia and loss of response (LOR) to biologic agents remains unclear. This study explored such an association in CD patients. This retrospective study included 94 CD patients who received biologic therapy. The skeletal muscle cross‐sectional area at the third lumbar was assessed by computed tomography or magnetic resonance imaging for sarcopenia evaluation. A LOR was defined by fecal calprotectin (FC) < 250 μg/g or >50% reduction from baseline levels or other factors, such as the used agent being replaced by other biologic agents. The association between sarcopenia and LOR was assessed by logistic regression analysis. LOR was observed in 54 patients (57.4%). The prevalence of sarcopenia in the LOR group was higher than that in response group (70.4% vs. 40.0%, p = 0.003). Sarcopenia (odds ratio [OR] = 3.89, 95% confidence interval [CI]: 1.31–11.54), Montreal L1 type (OR = 0.20, 95% CI: 0.06–0.60), perianal lesions (OR = 4.08, 95% CI: 1.31–12.70), and monocytes percentage (OR = 1.27, 95% CI: 1.02–1.57) at baseline were independent associated factors for LOR. Sarcopenia was also associated with LOR in patients who received infliximab (OR = 3.31, 95% CI: 1.11–9.87). Montreal L1 type, perianal lesions, and monocytes percentage (Model 1), and with additional consideration of sarcopenia (Model 2), were developed to predict LOR. Model 2 showed better performance than Model 1 (area under the curve [AUC] 0.82 vs. 0.75). Sarcopenia was associated with the LOR to biological agents or infliximab in adult patients with CD.