bluuebunny/crossref_metadata_2025_split huggingface dataset:
G protein-biased LPAR1 agonism promotes prototypic antidepressant effects
Authors: Kajitani Naoto , Okada-Tsuchioka Mami , Inoue Asuka , Miyano Kanako , Masuda Takeshi , Boku Shuken , Iwamoto Kazuya , Ohtsuki Sumio , Uezono Yasuhito , Aoki Junken , Takebayashi Minoru 
Published: November 2022

AbstractPrototypic antidepressants, such as tricyclic/tetracyclic antidepressants (TCAs), have multiple pharmacological properties and have been considered to be more effective than newer antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), in treating severe depression. However, the molecular mechanisms underlying the high efficacy of TCAs have not been completely understood. Herein, we found that lysophosphatidic acid receptor 1 (LPAR1), a G protein-coupled receptor, mediates the antidepressant effects of amitriptyline, a typical TCA. Amitriptyline directly bound to LPAR1 and activated downstream G protein signaling without affecting β-arrestin signaling, which implied that amitriptyline could act as a G protein-biased agonist of LPAR1. This biased agonism is unique to TCAs and has not been observed in other antidepressants, such as SSRIs. Long-term infusion of mouse hippocampus with 1-oleoyl-2-O-methyl-glycerophosphothionate (OMPT), a potent G protein-biased LPAR1 agonist, induced behavior similar to that induced by antidepressants. In contrast, LPA, a non-biased agonist of LPAR1, induced anxious behavior, indicating that LPAR1 may regulate conflicting emotional behaviors because of the downstream signaling bias. Furthermore, RNA-seq analysis revealed that LPA and OMPT have opposite patterns of gene expression changes in hippocampus. Ingenuity pathway analysis indicated that chronic intrahippocampal administration of OMPT could activate LPAR1 downstream signaling (Rho and MAPK), whereas LPA suppressed LPAR1 signaling. The results reveal the unique antidepressant effects of TCAs and indicate the potential of G protein-biased agonists of LPAR1 as targets for novel antidepressants.
Molecular determinants of fibrillation in a viral amyloidogenic domain from combined biochemical and biophysical studies
Authors: Nilsson Juliet F. , Baroudi Hakima , Gondelaud Frank , Pesce Giulia , Bignon Christophe , Ptchelkine Denis , Chamieh Joseph , Cottet Hervé , Kajava Andrey V. , Longhi Sonia 
Published: November 2022

AbstractThe Nipah and Hendra viruses (NiV and HeV)are biosafety level 4 human pathogens classified within theHenipavirusgenus of theParamyxoviridaefamily. In both NiV and HeV, the gene encoding the Phosphoprotein (P protein), an essential polymerase cofactor, also encodes the V and W proteins. These three proteins, which share an intrinsically disordered N-terminal domain (NTD) and have unique C-terminal domains (CTD), are all known to counteract the host innate immune response, with V and W acting by either counteracting or inhibiting Interferon (IFN) signaling. Recently, using a combination of biophysical and structural approaches, the ability of a short region within the shared NTD (PNT3 region) to form amyloid-like structures was reported. Here, we evaluated the relevance of each of three contiguous tyrosine residues located in a previously identified amyloidogenic motif (EYYY) within HeV PNT3 to the fibrillation process. Our results indicate that removal of a single tyrosine in this motif significantly decreases the ability to form fibrils independently of position, mainly affecting the elongation phase. In addition, we show that the C-terminal half of PNT3 has an inhibitory effect on fibril formation that may act as a molecular shield and could thus be a key domain in the regulation of PNT3 fibrillation. Finally, the kinetics of fibril formation for the two PNT3 variants with highest and lowest fibrillation propensity were studied by Taylor Dispersion Analysis (TDA). The results herein presented shed light onto the molecular mechanisms involved in fibril formation. In addition, the PNT3 variants we generated represent valuable tools to further explore the functional impact of V/W fibrillation in transfected and infected cells.
Adipose triglyceride lipase is regulated by CAMKK2-AMPK signaling and drives advanced prostate cancer
Authors: Awad Dominik , Pulliam Thomas L. , Spradlin Meredith , Cao Pham Hong-Anh , Subramani Elavarasan , Tellman Tristen V. , Ribeiro Caroline F. , Pakula Hubert , Ackroyd Jeffrey J. , Murray Mollianne M. , Han Jenny J. , Piyarathna Badrajee , Drake Justin M. , Ittmann Michael M. , Coarfa Cristian , Farach-Carson Mary C. , Loda Massimo , Eberlin Livia S. , Frigo Daniel E. 
Published: November 2022

SummaryLipid metabolism plays a central role in prostate cancer. To date, the major focus on prostate cancer lipid metabolism has centered onde novolipogenesis and lipid uptake with little consideration for how cancer cells access these lipids once they are created or taken up and stored. Patient-derived phosphoproteomics identified adipose triglyceride lipase (ATGL), a previously suspected tumor suppressor, as a CAMKK2-AMPK signaling target that, conversely, promotes castration-resistant prostate cancer (CRPC) progression. Phosphorylation of ATGL increased its lipase activity, cancer cell proliferation, migration, and invasion. Shotgun lipidomics and mass spectrometry imaging demonstrated ATGL’s profound regulation of lipid metabolismin vitroandin vivo, remodeling membrane composition. Inhibition of ATGL induced metabolic plasticity, causing a glycolytic shift that could be exploited therapeutically by co-targeting both metabolic pathways. Together, these data nominate ATGL and intracellular lipolysis as potential therapeutic targets for the treatment of CRPC and provide insights for future combination therapies.
Triggered Release from Thermosensitive Liposomes Improves Tumor Targeting of Vinorelbine
Authors: Regenold Maximilian , Kaneko Kan , Wang Xuehan , Peng H. Benson , Evans James C. , Bannigan Pauric , Allen Christine 
Published: November 2022

AbstractTriggered drug delivery strategies have been shown to enhance drug accumulation at target diseased sites in comparison to administration of free drug. In particular, many studies have demonstrated improved targetability of chemotherapeutics when delivered via thermosensitive liposomes. However, most studies continue to focus on encapsulating doxorubicin while many other drugs would benefit from this targeted and localized delivery approach. The proposed study explores the therapeutic potential of a thermosensitive liposome formulation of the commonly used chemotherapy drug vinorelbine in combination with mild hyperthermia (39-43 °C) in a murine model of rhabdomyosarcoma. Rhabdomyosarcoma, the most common soft tissue sarcoma in children, is largely treated using conventional chemotherapy which is associated with significant adverse long-term sequelae. In this study, mild hyperthermia was pursued as a non-invasive, non-toxic means to improve the efficacy and safety profiles of vinorelbine. Thorough assessment of the pharmacokinetics, biodistribution, efficacy and toxicity of vinorelbine administered in the thermosensitive liposome formulation was compared to administration in a traditional, non-thermosensitive liposome formulation. This study shows the potential of an advanced formulation technology in combination with mild hyperthermia as a means to target an untargeted therapeutic agent and result in a significant improvement in its therapeutic index.Graphical abstract
Corporate criminal liability in Islamic banks in Malaysia
Authors: Yusoff Nur Yusliana , Hassan Rusni 
Published: November 2022

PurposeThis paper aims to highlight provisions that may attract corporate criminal liability (CCL) in legislation and regulations enacted in Malaysia. Further, this paper identifies gaps or obstacles in the implementation of CCL in Islamic banks (IBs) in Malaysia.Design/methodology/approachThis research adopts the qualitative methodology. More specifically, it uses normative legal research by focusing on primary and secondary data obtained from legislation, regulations, decided case laws, guidelines, law textbooks and bank annual reports in relation to CCL provisions. It also conducts semi-structured interviews with different categories of experts, including legal practitioners (lawyers), regulators from Bank Negara Malaysia (BNM) and Securities Commission Malaysia, officers of the Attorney General's Chambers and officers from legal departments in IBs.FindingsThe results conclude that IBs should implement the law on CCL because they are considered corporations. It is also found that not all IBs complied with CCL provisions brought corporate offenders before the court.Research limitations/implicationsThis research is restricted by its specialisation in CCL in IBs in Malaysia.Practical implicationsThe CCL provision has to be implemented effectively by IBs to achieve the benefit. However, not all IBs implement CCL provision properly. The understanding created by the interview data illuminates the challenges in implementing CCL provisions. Thus, this paper seeks to change the approach in the implementation of CCL provisions by IBs in Malaysia.Originality/valueThe paper touches upon a new area, notably CCL in IBs, which is not well researched in past literature. Although there is a vast research on CCL, corporate crime in IBs in Malaysia is still an unexplored area. This study gives light on the implementation of CCL provisions in IBs.
Cultural practices and organizational ethnography: implications for fieldwork and research ethics
Authors: Alshallaqi Mohammad 
Published: November 2022

PurposeThis study focuses on the practical and ethical implications of the cultural practice of wasta for organizational ethnography in the Middle East. Wasta is a form of intercession rooted in the Middle Eastern cultural context and is similar to other cultural practices such as “guanxi” in China. Such practices do not only shape organizational lives in those contexts, but also how organizational ethnographies are designed and carried out.Design/methodology/approachThe data in this study are derived from field notes and the author’s reflections on the fieldwork of an organizational ethnography aimed to investigate a digital transformation project.FindingsThis study draws on the lens of positionality to illustrate how wasta helps favourably reconfigure a researcher’s positionality during interactions with gatekeepers and participants, thereby facilitating access and data collection. The study also presents the ethical concerns related to reciprocity triggered by wasta. Finally, this study demonstrates how wasta functions as a situated system to ensure ethical research practices.Originality/valueThe study demonstrates that it is inevitable that organizational ethnographers engage with cultural practices such as wasta or guanxi during fieldwork in such cultural contexts. Furthermore, the study provides theoretical and methodological contributions for future researchers by engaging in a reflexive exercise to present a more nuanced and theoretically informed understanding of wasta. Moreover, it shows how it is exercised during fieldwork, the ethical concerns inherent in its exercise and how they can be mitigated. The paper concludes with practical recommendations derived from this fieldwork experience for future research.
An examination of the institutional implication of the relationship between the managerial level of education and experience on firm innovation in Africa
Authors: Njinyah Sam Zisuh , Jones Sally , Alsiehemy Ali , Aldawaish Bader 
Published: November 2022

Purpose
Access to finance and corruption are two major institutional obstacles hindering firm innovation in Africa whose implication on the fit between managerial characteristics and firm innovation has not been examined. The purpose of this paper is to examine whether firms may want to hire managers with a good fit when faced with institutional constraints and the authors suggest managerial level of education and experience within an industry could play a vital role in helping such firms innovate.

Design/methodology/approach
Secondary data was obtained from the World Bank Enterprise Survey on 17 African countries and a series of hierarchical regression analyses were conducted to achieve the aim of the research.

Findings
The findings show that while managers with primary and secondary education had a negative relationship with firm innovation (product and process), managers with a university degree had a positive relationship. This relationship was also confirmed when the authors’ split the full sample into two sub-samples (the firms that are institutionally constrained by access to finance and corruption) and therefore confirm the institutional implications of managers fit for firm’s innovation.

Originality/value
While research on the effect of management characteristics on firm innovation has focused more on large firms and mostly from developed economies testing both direct and mediation effects, little research exists as to whether the institutional obstacles faced by small firms could influence the type of managers required to drive their innovation.
The impact of fast trains on tourism development in China: the role of local leaders
Authors: Deng Taotao , Dan Ting , Zhao Weishu 
Published: November 2022

Purpose
High-speed railway (HSR) substantially affects tourism development, but this impact remains somewhat controversial. This study aims to explore the HSR–tourism nexus from the perspective of Chinese local governance. In the context of promotion tournament model in China, this study attempts to explain such controversy by including local leaders.

Design/methodology/approach
Based on a data set from 25 cities in China’s Yangtze River Delta region during 2005–2019, this study uses a panel data regression model to examine local leaders’ moderating role in the HSR–tourism nexus.

Findings
The tenure of local leaders has a significant moderating role in the impact of HSR implementation on tourism development. Furthermore, a shorter leaders’ tenure strengthens the boost to tourism development from HSR service.

Originality/value
This paper enriches theoretical framework of leaders’ tournament theory. In addition, this study provides a new perspective to understand the HSR–tourism nexus better. This study identifies the moderating role of local leaders in the HSR–tourism nexus and expands the mechanism research of HSR–tourism nexus, which helps to explain the controversy of the HSR–tourism nexus.
Management of paediatric acute severe behavioural disturbance in emergency departments across Australia: A PREDICT survey of senior medical staff
Authors: Bourke Elyssia M , Knott Jonathan C , Craig Simon , Babl Franz E ,   the Paediatric Research in Emergency Departments International Collaborative (PREDICT) Research Network
Published: November 2022

AbstractObjectiveAcute severe behavioural disturbance (ASBD) is a condition seen with increasing frequency in EDs. It poses a significant risk to the patient and those around them. Little is known about the epidemiology or most effective management in the paediatric population. The aim of the present study is to clarify the practice of senior emergency doctors in Australia when managing paediatric ASBD.MethodsThe present study was a voluntary electronic questionnaire distributed to and undertaken by senior medical staff in EDs affiliated with the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network. Respondents reported on exposure to and confidence in managing paediatric ASBD and their current practices.ResultsA total of 227 (33%) clinicians completed the survey between February and May 2020. Most clinicians were caring for at least two young people with ASBD each week (72%), felt confident regarding the majority of components of management and referred to local clinical practice guidelines (69%). Agitation/sedation rating scales were seldom used (19%). There was a significant variation in self‐reported management practices. The choice of whether to use medication at all, the medication chosen and route of administration all varied greatly. Respondents were more willing to provide parenteral medication to young people reported as having recreational drug intoxication (84%) than those with neurodevelopment disorders (65%) when the same degree of agitation was reported.ConclusionsWithin Australia, there is considerable variation in paediatric ASBD practice, in particular regarding medication provision. Further prospective research is required to inform best clinical practice.
Outcome after veno‐venous extracorporeal membrane oxygenation in elderly compared to younger patients: A 14‐year retrospective observational study
Authors: Provaznik Zdenek , Philipp Alois , Müller Thomas , Kostiantyn Kozakov , Lunz Dirk , Schmid Christof , Floerchinger Bernhard 
Published: November 2022

AbstractBackgroundThe outcome after veno‐venous extracorporeal membrane oxygenation in elderly patients is supposed to be unsatisfactory. Our primary aim was to determine the influence of advanced age on short‐ and long‐term outcomes; the secondary aim was to analyze risk factors for impaired outcomes.MethodsBetween January 2006 and June 2020, 755 patients received V‐V ECMO support at our department. Patients were grouped according to age (18–49.9, 50–59.9, 60–69.9, ≥70 years old), and then retrospectively analyzed for short‐ and long‐term outcomes. Risk factors for in‐hospital mortality and death during follow‐up were assessed using multivariate regression analysis.ResultsDuration of V‐V ECMO support was comparable between all groups median (8–10 days, p = 0.256). Likewise, the weaning rate was comparable in all age groups 68.2%–76.5%; (p = 0.354), but in‐hospital mortality was significantly climbing with increasing age (<50 years 30.1%/n = 91 vs. 50–59.9 years 37.1%/n = 73, vs. 60–69.9 years 45.6%/n = 78 vs. ≥70 years 51.8%/n = 44; p < 0.001). Older age groups also showed significantly reduced cerebral performance category scores. The multivariate logistic analysis yielded age, acute and chronic hemodialysis, bilirubin on day 1 of support, malignancy, and primary lung disease as relevant risk factors for in‐hospital mortality. Age, coronary artery disease, presence of another primary lung disease, malignancy, and immunosuppression were risk factors for death during follow‐up.ConclusionIn V‐V ECMO patients, advanced age is associated with more comorbidity, impaired short‐ and long‐term outcome, and worse neurological outcome.
Early pregnancy triglycerides and not fructosamine are associated with birth weight (with foetal sexual dimorphism)
Authors: Isabel Clinck , Faro Rebecca Verelst , Vrijkotte Tanja G. M. , Theodorus Bartholomeus Twickler 
Published: November 2022

AbstractBackgroundWe evaluated whether maternal triglycerides (TGs) or fructosamine (measured in early pregnancy) predominantly contribute to birth weight (BW), in a foetal sexual dimorphism.MethodsAnalysis of data from the Amsterdam Born Children and their Development cohort study (total n = 3514). Maternal nonfasting TGs and fructosamine were determined in early gestation (median 13 weeks). Multivariable linear regression analysis was used to determine whether maternal TGs or fructosamine was associated with BW—small for gestational age (SGA)—large for gestational age (LGA) and whether it was sex‐dependent.ResultsWith each 1 mmol/L increase in TGs, BW increased significantly by 81.7 g. This increase was larger with boys (107.3 g; 95% CI 66–148) than girls (60.5 g; 95% CI 23.6–97.4). No association was found with fructosamine. When including different covariates (gestational age at blood sampling, total duration of pregnancy, maternal height, age, parity, ethnicity, educational level, smoking, alcohol, and pre‐pregnancy BMI), 29% of the variance in BW can be explained. Adding fructosamine to this model gave no added value in predicting BW, in contrast to adding TGs (R2 raised from 0.292 to 0.299, p < .001). The odds of a newborn LGA with higher maternal TG were increased (OR 1.6, 95% CI 1.3–2.0), in contrast to fructosamine.ConclusionsMaternal TGs were more dominant (compared to fructosamine) in its association with BW (measured in early physiological pregnancy) and more prominently present when carrying a male foetus. These remarkable observations warrant more future research, especially in obese patients at risk for gestational diabetes.
Inhibition of lipogenesis and sebum secretion for Lotus corniculatus seed extract in vitro and in vivo
Authors: Cheng Lu , Guo Jingyi , Lu Yina 
Published: November 2022

AbstractBackgroundBotanical ingredients are widely used in hair‐ and skin‐care products. However, few studies have investigated the effectiveness of botanical products on counteracting sebum synthesis and secretion.ObjectiveTo investigate the composition of Lotus corniculatus seed extract (LC) and its potential inhibition of lipogenesis in SZ95 sebocytes and oily human skin.MethodsThe active components of LC solutions were identified by high‐performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). The in vitro effects of LC were evaluated using SZ95 cells treated with linoleic acid (LA) and dihydrotestosterone (DHT) and incubated with LCs for 24 h and 72 h. Lipogenesis was assessed by Oil Red O and Nile Red staining of the cells. In vivo effects were assessed on 30 subjects with oily skin who were enrolled in a randomized, blank‐controlled trial and were treated with LC solution for 6 h and 4 weeks. The skin sebum contents and area on the forehead and cheeks were evaluated using a Sebumeter SM815 and Sebfix sebutape with Visioscan VC98. In addition, VISIA was used to collect half‐face photos for analysis.ResultsA novel active molecule, 5′‐o‐rhamnosyl uridine, was identified in LC. LC exhibited a dose‐dependent inhibitory effect on LA and DHT‐induced lipid synthesis. When 5% LC was applied for 3 h, the skin sebum contents and area were significantly reduced compared with the vehicle control, with an obvious reduction after 6 h. Continued use of the serum containing 5% LC for 4 weeks resulted in a significant reduction in the skin sebum contents and area. No adverse reactions were reported during the study.ConclusionsTopical application of LC resulted in an immediate and long‐lasting reduction of the sebum contents and area of oily human skin by reducing sebaceous lipogenesis through the LA and DHT pathways. This indicates the potential of LC as a new biological treatment for oily skin.