bluuebunny/crossref_metadata_2025_split huggingface dataset:
CX3CR1 Engagement by Respiratory Syncytial Virus Leads to Induction of Nucleolin and Dysregulation of Cilia-related Genes
Authors: Anderson Christopher S. , Chirkova Tatiana , Slaunwhite Christopher G. , Qiu Xing , Walsh Edward E. , Anderson Larry J. , Mariani Thomas J. 
Published: July 2020

AbstractRespiratory syncytial virus (RSV) contains a conserved CX3C motif on the ectodomain of the G-protein. The motif has been indicated as facilitating attachment of the virus to the host initiating infection via the human CX3CR1 receptor. The natural CX3CR1 ligand, CX3CL1, has been shown to induce signaling pathways resulting in transcriptional changes in the host cells. We hypothesize that binding of RSV to CX3CR1 via CX3C leads to transcriptional changes in host epithelial cells. Using transcriptomic analysis, the effect of CX3CR1 engagement by RSV was investigated. Normal human bronchial epithelial (NHBE) cells were infected with RSV virus containing either wildtype G-protein, or a mutant virus containing a CX4C mutation in the G-protein. RNA sequencing was performed on mock and 4-days-post-infected cultures. NHBE cultures were also treated with purified recombinant wild-type A2 G-protein. Here we report that RSV infection resulted in significant changes in the levels 766 transcripts. Many nuclear associated proteins were upregulated in the WT group, including Nucleolin. Alternatively, cilia-associated genes, including CC2D2A and CFAP221 (PCDP1), were downregulated. The addition of recombinant G-protein to the culture lead to the suppression of cilia-related genes while also inducing Nucleolin. Mutation of the CX3C motif (CX4C) reversed these effects on transcription decreasing nucleolin induction and lessening the suppression of cilia-related transcripts in culture. Furthermore, immunohistochemical staining demonstrated decreases in in ciliated cells and altered morphology. Therefore, it appears that engagement of CX3CR1 leads to induction of genes necessary for RSV entry as well as dysregulation of genes associated with cilia function.ImportanceRespiratory Syncytial Virus (RSV) has an enormous impact on infants and the elderly including increased fatality rates and potential for causing lifelong lung problems. Humans become infected with RSV through the inhalation of viral particles exhaled from an infected individual. These virus particles contain specific proteins that the virus uses to attach to human ciliated lung epithelial cells, initiating infection. Two viral proteins, G-protein and F-protein, have been shown to bind to human CX3CR1and Nucleolin, respectively. Here we show that the G-protein induces Nucleolin and suppresses gene transcripts specific to ciliated cells. Furthermore, we show that mutation of the CX3C-motif on the G-protein, CX4C, reverses these transcriptional changes.
A Murine Model for Enhancement ofStreptococcus pneumoniaePathogenicity Upon Viral Infection and Advanced Age
Authors: Joma Basma H. , Siwapornchai Nalat , Vanguri Vijay K. , Shrestha Anishma , Roggensack Sara E. , Davidson Bruce A. , Tai Albert K. , Hakansson Anders P. , Meydani Simin N. , Leong John M. , Ghanem Elsa N. Bou 
Published: July 2020

ABSTRACTStreptococcus pneumoniae(pneumococcus) resides asymptomatically in the nasopharynx but can progress from benign colonizer to lethal pulmonary or systemic pathogen. Both viral infection and aging are risk factors for serious pneumococcal infections. Previous work established a murine model that featured the movement of pneumococcus from the nasopharynx to the lung upon nasopharyngeal inoculation with influenza A virus (IAV) but did not fully recapitulate the severe disease associated with human co-infection. We built upon this model by first establishing pneumococcal nasopharyngeal colonization, then inoculating both the nasopharynx and lungs with IAV. In young (2 months) mice, co-infection triggered bacterial dispersal from the nasopharynx into the lungs, pulmonary inflammation, disease and mortality in a fraction of mice. In old mice (20-22 months), co-infection resulted in earlier and more severe disease. Aging was not associated with greater bacterial burdens but rather with more rapid pulmonary inflammation and damage. Both aging and IAV infection led to inefficient bacterial killing by neutrophilsex vivo. Conversely, aging and pneumococcal colonization also blunted IFN-α production and increased pulmonary IAV burden. Thus, in this multistep model, IAV promotes pneumococcal pathogenicity by modifying bacterial behavior in the nasopharynx, diminishing neutrophil function, and enhancing bacterial growth in the lung, while pneumococci increase IAV burden likely by compromising a key antiviral response. Thus, this model provides a means to elucidate factors, such as age and co-infection, that promote the evolution ofS. pneumoniaefrom asymptomatic colonizer to invasive pathogen, as well as to investigate consequences of this transition on antiviral defense.
The mecca of Cold War scholarship: Hong Kong as the intellectual hub to reveal China to the World
Authors: Lan Kenneth 
Published: July 2020

PurposeThis writing reveals Hong Kong’s role as the center of China research. Before Reform and Opening in 1979, the British colony was the only place in the world where all international China experts stopped over and obtained the latest and the most accurate accounts of PRC.Design/methodology/approachThe paper analyzes how Hong Kong serves as the intellectual mecca through examining the lives of China scholars amid building up their international profiles. What prompted them to join the China field? How were their lives like in the British crown colony? This paper also unveils the roles of the two research institutions played on Communist China studies: University Services Center (USC) and Union Research Institute (URI). In addition to relying on archival correspondences, personal interviews were also conducted in the last two years.FindingsDespite being the mecca of PRC research, Hong Kong was not the first destination for most aspiring China scholars from the West. Most of these Western scholars did not even plan to devote their whole working lives to the study of China. Through luck, draft avoidance and generous grants from Ford and Carnegie Foundations, these young men and women became internationally iconic figures of East Asian research. To complete their Ph.D. theses and subsequent China-related projects, Hong Kong was a “must-go” destination for them. Under the full protection of the Union Jack, these scholars enjoyed the freedom to speak, write, research and publish. God blessed Hong Kong with such a unique political status amid the Cold War.Originality/value155 Argyle Street was the Art Deco compound where Red China experts produced most groundbreaking scholarships. It was not only a two-story structure where they acquired their first-hand resources but a platform where any China-related topics were discussed openly under the auspices of British colonial rule of law. Despite claiming themselves as apolitical, both USC and URI were products of US containment policy against communism. Even so, the colonial government never prohibited the two’s operations. Through this paper, readers will also discover how young men and women became inspired into a career in China studies.
Addressing mentor wellbeing in practicum placement mentoring relationships in initial teacher education
Authors: Gillett-Swan Jenna , Grant-Smith Deanna 
Published: July 2020

PurposeUniversity-affiliated mentors serve as liaisons between schools and pre-service teachers during practicum placements, offering academic, administrative and relational support. In the context of academic workload intensification, increasing student numbers and the need to respond to issues as they occur in time-pressured environments, the wellbeing of mentors can become compromised. Mentor wellbeing is explored, highlighting corollary impacts of threats to pre-service teacher wellbeing on those who support them.Design/methodology/approachA descriptive single case-study explored mentor lived experiences of wellbeing during the pre-service teacher practicum placement and mentoring process. Semi-structured interviews were conducted with mentors supervising pre-service teacher professional experience placements. Adopting a shadowed data approach, mentors shared their own experiences and reflected on the experiences of others. Data was analysed using thematic content analysis.FindingsMentor and pre-service teacher wellbeing experiences exhibited similar wellbeing indicators, including personal and professional stress, workload strains and ethical dilemmas. Many mentors felt invisible in terms of supports for their own self-care as the focus was on meeting practicum stakeholder and student support needs rather than their own wellbeing.Originality/valueChanges to professional experience practices must consider potential impacts on pre-service teachers, in-school supervisors and the university-affiliated mentors as the wellbeing of each is potentially impacted the wellbeing of others in this professional experience triad. Increasing emphasis on work-integrated learning experiences across multiple disciplines invites future comparison and contrast of wellbeing experiences.
The germ of capitalism (Roman business through slave as the primordium of private enterprise) Part I. Above free labor
Authors: Petrosyan Armen E. 
Published: July 2020

PurposeThe purpose of this paper is to expose the pattern and mechanism of Roman private enterprise as the rudimentary form of capitalistic business.Design/methodology/approachBy means of historical analysis and theoretical reconstruction, the author retraces the background and foundations of business through slave as the initial stage of private enterprise.FindingsA comprehensive view of public and private entrepreneurship at the end of Republic and the beginning of Empire is presented. The riddle of “unnaturally” dear slaves in Rome (as compared with free labor and slaves in other countries of antiquity) is scrutinized. It is shown that “excessively” high demand for them was largely determined by their institutional worth: thanks todominica potestas, they appeared to be the key organizational resource for expanding private industrial business. The framework of private enterprise securing limited liability for owner and turning “business slave” into a kind of director is brought to light.Research limitations/implicationsThe results of this research allow historians to retrace the origins of modern private enterprise to classical antiquity, while economists and managers get an opportunity to better understand its nature and organizational status of those owning and managing it.Practical implicationsLeaders and executives can draw from the paper an object lesson of how, remaining within the existing political system, legal regulation and economic traditions, to make a radical innovation whose true meaning and social potential are so immense and far-reaching that get evident only many centuries later. The findings and conclusions the author comes to may be used in educational courses on economics, entrepreneurship, management, business history and so on.Social implicationsAn instructive model of conciliation of interests is scrutinized. “Directors” – those organizing and managing a business but not owning it – were, as well as workers, recruited by coercion and legal regimentation of their relations with proprietors. The polarization of their institutional roles was at the bottom of private enterprise from the very outset. The state created incentives for initiative and competent business men in subjection to well-offs to work hard, on one hand, and made their masters to use these incentives to public and their own profits. The benefits of all parties were taken into account, though, of course, not to the same degree. Thereby, a kind of social compromise embodied in a novel institution was attained to.Originality/valueThis paper is the first to demonstrate in relief the background and framework of Roman private enterprise as well as the functions and organizational status of its “director.”
Meaning of work in a group of school principals: the role of organizational variables
Authors: Buonomo Ilaria , Benevene Paula , Fiorilli Caterina 
Published: July 2020

Purpose
Principals’ beliefs about their profession are of great interest for schools in terms of organizational development and success. Furthermore, as meaning is a dimension of eudaimonic well-being, studying the principal meaning of work allows us to deepen the knowledge about their professional well-being, too. According to studies on non-educational contexts, the meaning of work is influenced by several organizational variables (such as possibilities for professional development and organizational commitment). Despite this, several school workers still lack to recognize the role played in this regard. Trying to fulfill these gaps partially, the purpose of this study is to verify the incremental effect of organizational dimensions and positive feedback from colleagues above and beyond positive beliefs about work.

Design/methodology/approach
An Italian version of the COPSOQ II adapted to school principals was administered to 1,616 school principals. Hierarchical multiple regression was conducted, considering three blocks of variables, namely, positive personal beliefs about work (job satisfaction and self-efficacy); organizational dimensions (role clarity, possibilities for development and sense of belonging to the workplace); positive feedback from colleagues.

Findings
Overall, the variables explained 45% of the variance of the meaning of work. While organizational variables accounted for an incremental 24% of the variance, above and beyond the personal experience of work (F (5, 1,610) = 267.378, p = 0.000), positive feedback from colleagues did not show a significant effect originality. To the best of the authors’ knowledge, this is the first study regarding the meaning of work at school with specific reference to school principals.

Originality/value
To the best of the authors’ knowledge, this is the first study regarding the meaning of work at school and with specific reference to school principals.
Newly identified genes contribute to vanillin tolerance in Saccharomyces cerevisiae
Authors: Liang Zhenzhen , Wang Xinning , Bao Xiaoming , Wei Tiandi , Hou Jin , Liu Weifeng , Shen Yu 
Published: July 2020

SummaryExploring the mechanisms of tolerance in microorganisms to vanillin, which is derived from lignin, will benefit the design of robust cell factories that produce biofuels and chemicals using lignocellulosic materials. Our objective was to identify the genes related to vanillin tolerance in Saccharomyces cerevisiae. We investigated the effects on vanillin tolerance of several genes that have site mutations in the highly vanillin‐tolerant strain EMV‐8 compared to its parental line NAN‐27. The results showed that overexpression of GCY1, a gene that encodes an aldo‐keto reductase that also has mRNA‐binding activity, YPR1, a paralog of GCY1 that encodes an aldo‐keto reductase, PEX5, a gene that encodes a peroxisomal membrane signal receptor and MBF1, a gene that encodes a multiprotein bridging factor increase the specific growth rates (μ) by 49%, 41%, 44% and 48 %, respectively, in medium containing 6 mmol l−1 vanillin. Among these gene products, Gcy1p and Ypr1p showed NADPH‐dependent and NAD(P)H‐dependent vanillin reductase activity, respectively. The reductase‐inactive mutant Gcy1pY56F also increased vanillin tolerance in S. cerevisiae, suggesting that other mechanisms exist. Although TRS85 and PEX5, genes for which the mRNAs are binding targets of Gcy1p, were shown to be related to vanillin tolerance, both the mRNA and protein levels of these genes were not changed by overexpression of GCY1. The relationship between the mRNA‐binding activity of Gcy1p and its positive effect on vanillin tolerance is still not clear. Finally, we found that the point mutation D112A in Mbf1p, which disrupts the binding of Mbf1p and the TATA element‐binding protein (TBP), did not decrease the positive effect of Mbf1p on vanillin tolerance. This indicates that the binding of Mbf1p and TBP is not necessary for the positive effect on vanillin tolerance mediated by Mbf1p. We have successfully identified new genes related to vanillin tolerance and provided novel targets that can be used to improve the vanillin tolerance of S. cerevisiae. Moreover, we have extended our understanding of the proteins encoded by these genes.
Pain response and quality of life assessment in patients with moderate/severe neuropathic pain due to bone metastasis undergoing treatment with palliative radiotherapy and tapentadol: A prospective multicentre pilot study
Authors: Cacicedo Jon , Ciria Juan Pablo , Morillo Virginia , Martinez‐Indart Lorea , Gómez‐Iturriaga Alfonso , del Hoyo Olga , Büchser David , Frias Andere , San Miguel Iñigo , Suarez Fernan , Casquero Francisco 
Published: July 2020

AbstractIntroductionTo assess pain response rate (RR) and quality of life (QoL), in patients with moderate/severe neuropathic pain (NP) due to bone metastasis (BM) undergoing palliative 3D radiotherapy plus tapentadol.MethodsWe conducted a prospective multicentre pilot study. Patients were assessed before radiotherapy using the validated questionnaire (Douleur Neuropathique en 4 questions). Response to radiotherapy (8 Gy–30 Gy/1–10fr) at one and two months was assessed according the International Bone Metastases Consensus criteria. Inclusion criteria: radiological evidence of BM, NP according to DN4 (cut‐off score ≥ 4), no spinal cord compression, worst pain score ≥ 5/10. Nonparametric Mann–Whitney U test compared changes in QoL among response groups.ResultsSeventeen patients (13 men, 4 woman), median age 67 years (42–81), were included. Pre‐treatment median pain severity was 7.5 (5–10). Median dose of tapentadol administered before radiotherapy was 100 mg/24 h (100–300 mg). Overall RR 1 month after radiotherapy was 10/16 = 62.5%: 3/16 (18.8%) achieving a complete response (CR) and 7/16 (43.8%) a partial response (PR). Overall RR 2 months after RT was 5/10 (50%): 10% a CR and 40% a PR. ITT RR for this study at 1 and 2 months was 10/17 = 59% and 5/17 = 29%, respectively. Patients responding to radiotherapy had significant improvement in EORTC QLQ‐C30 emotional functioning (EF) (p = 0.025) and fatigue symptom scale scores (p = 0.035) one month after radiotherapy. Painful site symptom QLQ‐BM22 scores improved 2 months after radiotherapy (p = 0.024).ConclusionsPalliative radiotherapy plus tapentadol shows an acceptable pain response and QoL improvement especially regarding EF, fatigue and painful site symptom scales in patients with moderate/severe NP due to BM. Therefore, it could be an alternative to manage NP in daily practice.
Dignity, Inequality, and the Populist Backlash: Lessons from America and Europe for a Sustainable Globalization
Authors: Abdelal Rawi 
Published: July 2020

AbstractThe greatest challenge to the sustainability of our current era of globalization comes from within the United States. Most Americans have come to reject globalization. We must discern the lessons from the parts of the developed world where the backlash is also profound – France, for example – and where it has been more muted – such as Germany. In both the United States and France, gross Gini coefficients have increased sharply during the past thirty or so years. The French state has, however, delivered a net, after‐tax, after‐transfer distribution of income that is more equal than it was thirty years ago. And yet: France is still in the midst of an anti‐systemic populist revolt. There is only one inescapable conclusion: it is not just about the money. Those who feel left behind in both countries feel that they have lost respect and dignity. We cannot redistribute our way out of the crisis of global capitalism. The German experience holds lessons. We must value and valorize the many ways in which people contribute. We must also pursue policies that create patterns of employment that confer dignity, meaning, and purpose. I argue for dignity as a tool of policy, beyond its normative desirability as a goal.
Status of 10 targeted genes of non‐small cell lung cancer in eastern China: A study of 884 patients based on NGS in a single institution
Authors: Li Dan , Ding Li , Ran Wenwen , Huang Yan , Li Guangqi , Wang Chengqin , Xiao Yujing , Wang Xiaonan , Lin Dongliang , Xing Xiaoming 
Published: July 2020

BackgroundThe status of targeted genes and the association between targeted genes and clinicopathological features in Chinese lung cancer patients remains to be elucidated.MethodsThe status of 10 targeted genes was evaluated by next‐generation sequencing (NGS) in 884 non‐small cell lung cancer (NSCLC) patients. The relationship between gene alterations and clinicopathological characters was analyzed.ResultsOverall, 684 (77.4%) patients harbored gene alterations, and EGFR (510, 57.7%) was found to be the most common type of mutation followed by KRAS (91, 10.3%), HER2 (38, 4.3%), PIK3CA (32, 3.6%), ALK (21, 2.4%), BRAF (10, 1.1%), ROS1 (5, 0.6%), RET (5, 0.6%), MET (4, 0.5%) and NRAS (1, 0.1%). Gene alterations were more frequent in females, non‐smokers and adenocarcinoma (P < 0.001). EGFR mutations were associated with women, non‐smokers, normal level of serum tumor markers, and adenocarcinoma (P < 0.001). Patients without lymph node metastasis (P = 0.012), or early stage disease (P < 0.001) exhibited a higher EGFR mutation rate. KRAS mutations tended to arise in men (P < 0.001), smokers (P < 0.001) and patients with higher levels of serum tumor markers (P = 0.048). A mucus‐producing component was associated with KRAS (P < 0.001), ROS1 (P = 0.033) and ALK (P < 0.001) alterations. ALK and ROS1 rearrangements were more frequent in micropapillary structures (P = 0.004, P = 0.012). BRAF mutation was associated with advanced disease patients and micropapillary structure (P < 0.001). PIK3CA mutation was more likely to be found in elderly patients (P = 0.014). Some patients had synchronous gene alterations, including EGFR/PIK3CA, EGFR/HER2, HER2/KRAS, EGFR/KRAS, EGFR/ROS1, EGFR/NRAS, KRAS/PIK3CA, KRAS/PIK3CA/HER2.ConclusionsMost patients had at least one genetic alteration, and individual patients harbored synchronous mutation. Each gene alteration had unique clinicopathological characteristics.Key pointsSignificant findings of the studyThis study revealed the frequency and distribution of 10 targeted gene abnormalities and their association with clinicopathological parameters of Chinese non‐small cell lung cancer (NSCLC) patients in eastern China.What this study addsSome rare synchronous mutations were detected in our study by next‐generation sequencing (NGS).
Mechanisms by which autophagy regulates memory capacity in ageing
Authors: De Risi Maria , Torromino Giulia , Tufano Michele , Moriceau Stéphanie , Pignataro Annabella , Rivagorda Manon , Carrano Nicolò , Middei Silvia , Settembre Carmine , Ammassari‐Teule Martine , Gardoni Fabrizio , Mele Andrea , Oury Franck , De Leonibus Elvira 
Published: July 2020

AbstractAutophagy agonists have been proposed to slow down neurodegeneration. Spermidine, a polyamine that acts as an autophagy agonist, is currently under clinical trial for the treatment of age‐related memory decline. How Spermidine and other autophagy agonists regulate memory and synaptic plasticity is under investigation. We set up a novel mouse model of mild cognitive impairment (MCI), in which middle‐aged (12‐month‐old) mice exhibit impaired memory capacity, lysosomes engulfed with amyloid fibrils (β‐amyloid and α‐synuclein) and impaired task‐induced GluA1 hippocampal post‐translation modifications. Subchronic treatment with Spermidine as well as the autophagy agonist TAT‐Beclin 1 rescued memory capacity and GluA1 post‐translational modifications by favouring the autophagy/lysosomal‐mediated degradation of amyloid fibrils. These findings provide new mechanistic evidence on the therapeutic relevance of autophagy enhancers which, by improving the degradation of misfolded proteins, slow down age‐related memory decline.