bluuebunny/crossref_metadata_2025 huggingface dataset:
FLCN Gene Ablation Reduces Fibrosis and Inflammation in a Diet-Induced NASH Model
Authors: Paquette Mathieu , Yan Ming , El-Houjeiri Leeanna , Biondini Marco , Ramírez-Reyes Josué M. J. , Pacis Alain , Jeong Hyeonju , Estall Jennifer L. , Siegel Peter M. , Pause Arnim
Published: September 2020

Non-alcoholic steatohepatitis (NASH) represents a major economic burden and is characterized by triglyceride accumulation, inflammation, and fibrosis. No pharmacological agents are currently approved to treat this condition. Emerging data suggests an important role of autophagy in this condition, which serves to degrade intracellular lipid stores, reduce hepatocellular damage, and dampen inflammation. Autophagy is primarily regulated by the transcription factors TFEB and TFE3, which are negatively regulated by mTORC1. Given that FLCN is an mTORC1 activator via its GAP activity towards RagC/D, we generated a liver specific Flcn knockout mouse model to study its role in NASH progression. We demonstrate that loss of FLCN results in reduced triglyceride accumulation, fibrosis, and inflammation in mice exposed to a NASH-inducing diet. Hence, the GAP activity of FLCN could a promising target for small molecule drugs to treat NASH progression by specifically activating autophagy and lysosomal biogenesis while leaving mRNA translation machinery unperturbed. Collectively, these results show an unexpected role for FLCN in NASH progression and highlight new possibilities for treatment strategies through its role in hepatocyte homeostasis.
Simultaneous aerosol and intra-muscular immunization with influenza vaccine induces powerful protective local T cell and systemic Ab immune responses in pigs
Authors: Martini Veronica , Paudyal Basu , Chrun Tiphany , McNee Adam , Edmans Matthew , Maze Emmanuel , Clark Beckie , Nunez Alejandro , Dolton Garry , Sewell Andrew , Beverley Peter , MacLoughlin Ronan , Townsend Alain , Tchilian Elma
Published: September 2020

A vaccine providing both powerful antibody and cross-reactive T cell immune responses against influenza viruses would be beneficial for both humans and pigs. Here we evaluated intramuscular (IM), aerosol (Aer) and simultaneous immunization (SIM) by both routes in pigs, using the single cycle candidate influenza vaccine S-FLU. After prime and boost immunization pigs were challenged with H1N1pdm09 virus. IM immunized pigs generated high titer of neutralizing antibodies but poor T cell responses, while Aer induced powerful respiratory tract T cell responses, but a low titer of antibodies. SIM pigs combined high antibody titers and strong local T cell responses. SIM pigs showed the most complete suppression of virus shedding and the greatest improvement in pathology. We conclude that SIM regimes for immunization against respiratory pathogens warrant further study.
Computational 4D-OCM for label-free imaging of collective cell invasion and force-mediated deformations in collagen
Authors: Mulligan Jeffrey A. , Ling Lu , Fischbach Claudia , Adie Steven G.
Published: September 2020

Traction force microscopy (TFM) is an important family of techniques used to measure and study the role of cellular traction forces (CTFs) associated with many biological processes. However, current standard TFM methods rely on imaging techniques that do not provide the experimental capabilities necessary to study CTFs within 3D collective and dynamic systems embedded within optically scattering media. Traction force optical coherence microscopy (TF-OCM) was developed to address these needs, but has only been demonstrated for the study of isolated cells embedded within optically clear media. Here, we present computational 4D-OCM methods that enable the study of dynamic invasion behavior of large tumor spheroids embedded in collagen. Our multi-day, time-lapse imaging data provided detailed visualizations of evolving spheroid morphology, collagen degradation, and collagen deformation, all using label-free scattering contrast. These capabilities, which provided insights into how stromal cells affect cancer progression, significantly expand access to critical data about biophysical interactions of cells with their environment, and lay the foundation for future efforts toward volumetric, time-lapse reconstructions of collective CTFs with TF-OCM.
Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences
Authors: Karasik Agnes , Jones Grant D. , DePass Andrew V. , Guydosh Nicholas R.
Published: September 2020

Ribonuclease L (RNase L) is activated as part of the innate immune response and plays an important role in the clearance of viral infections. When activated, it endonucleolytically cleaves both viral and host RNAs, leading to a global reduction in protein synthesis. However, it remains unknown how widespread RNA decay, and consequent changes in the translatome, promote the elimination of viruses. To study how this altered transcriptome is translated, we assayed the global distribution of ribosomes in RNase L activated human cells with ribosome profiling. We found that RNase L activation leads to a substantial increase in the fraction of translating ribosomes in ORFs internal to coding sequences (iORFs) and ORFs within 5’ and 3’ UTRs (uORFs and dORFs). Translation of these alternative ORFs was dependent on RNase L’s cleavage activity, suggesting that mRNA decay fragments are translated to produce short peptides that may be important for antiviral activity.
Molecular basis for SARS-CoV-2 spike affinity for human ACE2 receptor
Authors: Delgado Julián M. , Duro Nalvi , Rogers David M. , Tkatchenko Alexandre , Pandit Sagar A. , Varma Sameer
Published: September 2020

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused substantially more infections, deaths, and economic disruptions than the 2002-2003 SARS-CoV. The key to understanding SARS-CoV-2’s higher infectivity may lie in its host receptor recognition mechanism. This is because experiments show that the human ACE2 protein, which serves as the primary receptor for both CoVs, binds to CoV-2’s spike protein 5-20 fold stronger than SARS-CoV’s spike protein. The molecular basis for this difference in binding affinity, however, remains unexplained and, in fact, a comparison of X-ray structures leads to an opposite proposition. To gain insight, we use all-atom molecular dynamics simulations. Free energy calculations indicate that CoV-2’s higher affinity is due primarily to differences in specific spike residues that are local to the spike-ACE2 interface, although there are allosteric effects in binding. Comparative analysis of equilibrium simulations reveals that while both CoV and CoV-2 spike-ACE2 complexes have similar interfacial topologies, CoV-2’s spike protein engages in greater numbers, combinatorics and probabilities of hydrogen bonds and salt bridges with ACE2. We attribute CoV-2’s higher affinity to these differences in polar contacts, and these findings also highlight the importance of thermal structural fluctuations in spike-ACE2 complexation. We anticipate that these findings will also inform the design of spike-ACE2 peptide blockers that, like in the cases of HIV and Influenza, can serve as antivirals.
Microbial colonization induces histone acetylation critical for inherited gut-germline-neural signaling
Authors: Hong Chunlan , Lalsiamthara Jonathan , Ren Jie , Sang Yu , Aballay Alejandro
Published: September 2020

The gut-neural axis plays a critical role in the control of several physiological processes, including the communication of signals from the microbiome to the nervous system, which affects learning, memory, and behavior. However, the pathways involved in gut-neural signaling of gut-governed behaviors remain unclear. We found that the intestinal distension caused by the bacteriumPseudomonas aeruginosainduces histone H4 Lys8 acetylation (H4K8ac) in the germline ofCaenorhabditis elegans, which is required for both a bacterial aversion behavior and its transmission to the next generation. We show that induction of H4K8ac in the germline is essential for bacterial aversion and that a 14-3-3 chaperone protein family member, PAR-5, is required for H4K8ac. Our findings highlight a role for H4K8ac in the germline not only in the intergenerational transmission of pathogen avoidance but also in the transmission of pathogenic cues that travel through the gut-neural axis to control the aversive behavior.
Arabidopsis thalianazinc accumulation in leaf trichomes is correlated with zinc concentration in leaves
Authors: Ricachenevsky Felipe K. , Punshon Tracy , Salt David E. , Fett Janette P. , Guerinot Mary Lou
Published: September 2020

Zinc (Zn) is a key micronutrient. In humans, Zn deficiency is a common nutritional disorder, and most people acquire dietary Zn from eating plants. In plants, Zn deficiency can decrease plant growth and yield. Understanding Zn homeostasis in plants can improve agriculture and human health. While root Zn transporters in plat model species have been characterized in detail, comparatively little is known about shoot processes controlling Zn concentrations and spatial distribution. Previous work showed that Zn hyperaccumulator species such asArabidopsis halleriaccumulate Zn and other metals in leaf trichomes. The model speciesArabidopsis thalianais a non-accumulating plant, and to date there is no systematic study regarding Zn accumulation inA. thalianatrichomes. Here, we used Synchrotron X-Ray Fluorescence mapping to show that Zn accumulates at the base of trichomes ofA. thaliana, as had seen previously for hyperaccumulators. Using transgenic and natural accessions ofA. thalianathat vary in bulk leaf Zn concentration, we demonstrated that higher leaf Zn increases total Zn found at the base of trichome cells. Furthermore, our data suggests that Zn accumulates in the trichome apoplast, likely associated with the cell wall. Our data indicates that Zn accumulation in trichomes is a function of the Zn status of the plant, and provides the basis for future studies on a genetically tractable plant species aiming at understanding the molecular steps involved in Zn spatial distribution in leaves.
Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk
Authors: Vazquez Juan Manuel , Lynch Vincent J.
Published: September 2020

The risk of developing cancer is correlated with body size and lifespan within species. Between species, however, there is no correlation between cancer and either body size or lifespan, indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Elephants and their relatives (Proboscideans) are a particularly interesting lineage for the exploration of mechanisms underlying the evolution of augmented cancer resistance because they evolved large bodies recently within a clade of smaller bodied species (Afrotherians). Here, we explore the contribution of gene duplication to body size and cancer risk in Afrotherians. Unexpectedly, we found that tumor suppresxssor duplication was pervasive in Afrotherian genomes, rather than restricted to Proboscideans. Proboscideans, however, have duplicates in unique pathways that may underlie some aspects of their remarkable anti-cancer cell biology. These data suggest that duplication of tumor suppressor genes facilitated the evolution of increased body size by compensating for decreasing intrinsic cancer risk.
Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours
Authors: Thomas Catherine S. , Mohammadkhani Aida , Rana Madiha , Qiao Min , Baimel Corey , Borgland Stephanie L.
Published: September 2020

Reward and reinforcement processes are critical for survival and propagation of genes. While numerous brain systems underlie these processes, a cardinal role is ascribed to mesolimbic dopamine. However, ventral tegmental area (VTA) dopamine neurons receive complex innervation and various neuromodulatory factors, including input from lateral hypothalamic (LH) orexin/hypocretin neurons which also express and co-release the neuropeptide, dynorphin. Dynorphin in the VTA induces aversive conditioning through the Kappa opioid receptor (KOR) and decreases dopamine when administered intra-VTA. Exogenous application of orexin or orexin 1 receptor (oxR1) antagonists in the VTA bidirectionally modulates dopamine-driven motivation and reward-seeking behaviours, including the attribution of motivational value to primary rewards and associated conditioned stimuli. However, the effect of endogenous stimulation of LH orexin/dynorphin-containing projections to the VTA and the potential contribution of co-released dynorphin on mesolimbic dopamine and reward related processes remains uncharacterised. We combined optogenetic, electrochemical, and behavioural approaches to examine this. We found that optical stimulation of LH orexin/dynorphin inputs in the VTA potentiates mesolimbic dopamine neurotransmission in the nucleus accumbens (NAc) core, produces real time and conditioned place preference, and increases the food cue-directed orientation in a Pavlovian conditioning procedure. LH orexin/dynorphin potentiation of NAc dopamine release and real time place preference was blocked by an oxR1, but not KOR antagonist. Thus, rewarding effects associated with optical stimulation of LH orexin/dynorphin inputs in the VTA are predominantly driven by orexin rather than dynorphin.
Switch-1 Instability at the Active Site Decouples ATP Hydrolysis from Force Generation in Myosin II
Authors: Walker Benjamin C. , Walczak Claire E. , Cochran Jared C.
Published: September 2020

Myosin active site elements (i.e. switch-1) bind both ATP and a divalent metal to coordinate ATP hydrolysis. ATP hydrolysis at the active site is linked via allosteric communication to the actin polymer binding site and lever arm movement, thus coupling the free energy of ATP hydrolysis to force generation. How active site motifs are functionally linked to actin binding and the power stroke is still poorly understood. We hypothesize that destabilizing switch-1 movement at the active site will negatively affect the tight coupling of ATP hydrolysis to force production. Using a metal-switch system, we tested the effect of interfering with switch-1 coordination of the divalent metal cofactor on force generation. We found that while ATPase activity increased, motility was inhibited. Our results demonstrate that a single atom change that affects the switch-1 interaction with the divalent metal directly regulates actin binding and force generation. Even slight modification of the switch-1 divalent metal coordination can decouple ATP hydrolysis from motility. Switch-1 movement is therefore critical for both structural communication with the actin binding site, as well as coupling the energy of ATP hydrolysis to force generation.
Evolution of Boldness and Exploratory Behavior in Giant Mice from Gough Island
Authors: Stratton Jered A. , Nolte Mark J. , Payseur Bret A.
Published: September 2020

Island populations are hallmarks of extreme phenotypic evolution. Radical changes in resource availability and predation risk accompanying island colonization drive changes in behavior, which Darwin likened to tameness in domesticated animals. Although many examples of animal boldness are found on islands, the heritability of observed behaviors, a requirement for evolution, remains largely unknown. To fill this gap, we profiled anxiety and exploration in island and mainland inbred strains of house mice raised in a common laboratory environment. The island strain was descended from mice on Gough Island, the largest wild house mice on record. Experiments utilizing open environments across two ages showed that Gough Island mice are bolder and more exploratory, even when a shelter is provided. Concurrently, Gough Island mice retain an avoidance response to predator urine. F1 offspring from crosses between these two strains behave more similarly to the mainland strain for most traits, suggesting recessive mutations contributed to behavioral evolution on the island. Our results provide a rare example of novel, inherited behaviors in an island population and demonstrate that behavioral evolution can be specific to different forms of perceived danger. Our discoveries pave the way for a genetic understanding of how island populations evolve unusual behaviors.
A reduction in voluntary physical activity during pregnancy in mice is mediated by prolactin
Authors: Ladyman S.R. , Carter K.M. , Aung Z. Khant , Grattan D. R.
Published: September 2020

As part of the maternal adaptations to pregnancy, mice show a rapid, profound reduction in voluntary running wheel activity (RWA) as soon as pregnancy is achieved. Here, we evaluate the hypothesis that prolactin, one of the first hormones to change secretion pattern following mating, is involved in driving this suppression of physical activity levels during pregnancy. We show that prolactin can acutely suppress RWA in virgin female mice, and that conditional deletion of prolactin receptors (Prlr) from either all forebrain neurons or from GABA neurons prevented the early pregnancy-induced suppression of RWA. Deletion of Prlr specifically from the medial preoptic area, a brain region associated with multiple homeostatic and behavioural roles including parental behaviour, completely abolished the early pregnancy-induced suppression of RWA. Our data demonstrate a key role for prolactin in suppressing voluntary physical activity during early pregnancy, highlighting a novel biological basis for reduced physical activity in pregnancy.
Deep-sea mussels from a hybrid zone on the Mid-Atlantic Ridge host genetically indistinguishable symbionts
Authors: Ücker Merle , Ansorge Rebecca , Sato Yui , Sayavedra Lizbeth , Breusing Corinna , Dubilier Nicole
Published: September 2020

The composition and diversity of animal microbiomes is shaped by a variety of factors, many of them interacting, such as host traits, the environment, and biogeography. Hybrid zones, in which the ranges of two host species meet and hybrids are found, provide natural experiments for determining the drivers of microbiome communities, but have not been well studied in marine environments. Here, we analysed the composition of the symbiont community in two deep-sea,Bathymodiolusmussel species along their known distribution range at hydrothermal vents on the Mid-Atlantic Ridge, with a focus on the hybrid zone where they interbreed. In-depth metagenomic analyses of the sulphur-oxidising symbionts of 30 mussels from the hybrid zone, at a resolution of single nucleotide polymorphism analyses of ∼2500 orthologous genes, revealed that parental and hybrid mussels have genetically indistinguishable symbionts. While host genetics does not appear to affect symbiont composition in these mussels, geographic location of the mussels on the Mid-Atlantic Ridge explained 45 % of symbiont genetic variability based on redundancy analyses. We hypothesize that geographic structuring of the free-living symbiont population plays a major role in driving the composition of the microbiome in these deep-sea mussels.
Temporal trait plasticity and neighborhood crowding predict the growth of tropical trees
Authors: Asefa Mengesha , Song Xiaoyang , Cao Min , Lasky Jesse R. , Yang Jie
Published: September 2020

Functional traits and neighborhood composition have been used to predict tree growth dynamics. Temporal changes in trait values (temporal trait plasticity) is one of the mechanisms for adaptive plastic response to environmental change. However, the consequence of temporal change in trait values and neighborhoods on the growth performance of individuals has rarely been investigated. We, therefore tested the effect of temporal changes in trait values and neighborhood crowding on the growth rate of individuals in a tropical forest using a dataset containing individual level growth and functional trait data forFicusindividuals. We collected trait and size data at two time points (2010 and 2017) for 472 individuals of 15Ficusspecies in Xishuangbanna tropical forest dynamics plot, southwest China. We used linear mixed effect model to predict the effect of temporal trait plasticity and neighborhood crowding on the relative growth rate of individuals using these data. We found significant temporal changes in individuals’ functional traits suggesting a shift in ecological strategies from being functionally acquisitive to conservative. We also found differences in neighborhood crowding between the two census years indicating that the strength of individual interactions might change over time. The temporal changes in trait values and neighborhood crowding were found to predict better the relative growth rate of individuals, compared to static trait or crowding values in the initial and final censuses. We also found major axes of tree functional strategies in a principal component analysis, highlighting potentially adaptive trait differences. Our results in general highlight to consider the temporal dimension of functional traits and biotic interactions, as our result suggest that growth-trait relationships may vary between time points, allowing us to understand the demographic response of species to temporal environmental change.
Feature-specific reaction times reveal a semanticisation of memories over time and with repeated remembering
Authors: Lifanov Julia , Linde-Domingo Juan , Wimber Maria
Published: September 2020

Memories are thought to undergo an episodic-to-semantic transformation in the course of their consolidation. We here tested if repeated recall induces a similar semanticization, and if the resulting qualitative changes in memories can be measured using simple feature-specific reaction time probes. Participants studied associations between verbs and object images, and then repeatedly recalled the objects when cued with the verb, immediately and after a two-day delay. Reaction times during immediate recall demonstrated that conceptual features were accessed faster than perceptual features. Consistent with a semanticization process, this perceptual-conceptual gap significantly increased across the delay. A significantly smaller perceptual-conceptual gap was found in the delayed recall data of a control group who repeatedly studied the verb-object pairings on the first day, instead of actively recalling them. Our findings suggest that wake recall and offline consolidation interact to transform memories over time, strengthening meaningful semantic information over perceptual detail.
Canonical goal-selective representations are absent from prefrontal cortex in a spatial working memory task requiring behavioral flexibility
Authors: Böhm Claudia , Lee Albert K.
Published: September 2020

The prefrontal cortex (PFC)’s functions are thought to include working memory, as its activity can reflect information that must be temporarily maintained to realize the current goal. We designed a flexible spatial working memory task that required rats to navigate - after distractions and a delay - to multiple possible goal locations from different starting points and via multiple routes. This made the current goal location the key variable to remember, instead of a particular direction or route to the goal. However, across a broad population of PFC neurons, we found no evidence of current-goal-specific memory in any previously reported form - i.e. differences in the rate, sequence, phase or covariance of firing. This suggests such patterns do not hold working memory in the PFC when information must be employed flexibly. Instead, the PFC grouped locations representing behaviorally equivalent task features together, consistent with a role in encoding long-term knowledge of task structure.
Rietveld refinement of the langbeinite-type phosphate K2Ni0.5Hf1.5(PO4)3
Authors: Zhou Liang , Butenko Denys S. , Ogorodnyk Ivan V. , Klyui Nickolai I. , Zatovsky Igor V.
Published: September 2020

Polycrystalline potassium nickel(II) hafnium(IV) tris(orthophosphate), a langbeinite-type phosphate, was synthesized by a solid-state method. The three-dimensional framework of the title compound is built up from two types of [MO6] octahedra [the M sites are occupied by Hf:Ni in ratios of 0.754 (8):0.246 (8) and 0.746 (8):0.254 (8), respectively] and [PO4] tetrahedra are connected via O vertices. The K+ cations are located in two positions within large cavities of the framework, having coordination numbers of 9 and 12. The Hf, Ni and K sites lie on threefold rotation axes, while the P and O atoms are situated in general positions.
6-(3,4-Difluorophenyl)-7,8,13,14-tetrahydrodibenzo[c,k]phenanthridine
Authors: Fang Yiwen , Liu Bingbing , Jia Zhixiang
Published: September 2020

In the title compound, C27H19F2N, the five-fused-ring system is highly puckered and the dihedral angle between the central pyridine ring and pendant difluorobenzene ring is 45.12 (12)°. In the crystal, inversion dimers linked by pairwise weak C—H...N hydrogen bonds generate R
2
2(12) loops and the dimers are further linked by weak C—H...F interactions to form [\overline{1}01] chains.
Patidar Exports Private Limited
Authors: Varma Poornima , Jena Sanjay Kumar
Published: September 2020

During 2016, Vishant Patel, the founder of Patidar Exports Private Limited (PEPL), an export firm for cotton and other products in Ahmedabad, was planning to export raw cotton to more countries, though he had already exported cotton to countries like China, Bangladesh, Pakistan and Vietnam. He found that Indonesia, Turkey and Thailand were potential markets. However, each market had its peculiarities. In one market the opportunities were good, but the entry regulations were stringent, whereas in another market the regulations were relaxed, but the competition was intense. He was wondering which market to enter.
Nestlé entangled! Braving the Maggi Noodle Crisis in India
Authors: Kaul Asha , Chaudhri Vidhi
Published: September 2020

The case explicates a situation wherein an international flight from Newark to Ahmedabad, with a stopover in Mumbai, is delayed during the final leg of its journey between Mumbai and Ahmedabad. The situation is further exacerbated by the fact that all international and domestic passengers are already on board when they face this five-hour delay. The case provides a rich context to discuss issues related to difficult communication and persuasion during crisis. The captain communicates with the passengers, through a series of announcements, with updates on the situation. He attempts to manage the escalating tension within the airplane and does succeed to a certain level. The case highlights the significance of timely and well-crafted messages during crisis situations. It also illuminates how the use of rhetorical strategies influence customer perception of credibility and at times, shift attribution of blame.
Backcasting for desirable futures in Finnish forest-based firms
Authors: Näyhä Annukka
Published: September 2020

Purpose

In Finland, new forest-based sector (FBS) businesses are seen as important for the transition to the circular bioeconomy. The purpose of this study is to explore the transition of Finnish FBS companies to new business models. The aim is to understand how FBS companies define their ideal future states and related business models for the year 2030.

Design/methodology/approach

This study uses thematic interviews with managers from various FBS firms and companies from interfacing sectors. In the interviews, the key idea of backcasting was pursued when respondents discussed the desirable future states of their business.

Findings

The effort to achieve growth of the business and the appearance of new products characterize the company-specific desirable future states. In these desirable futures, expanded businesses will be based on strong knowledge. Resource efficiency and collaboration create a strong basis for the desirable future state of the whole FBS to create a sustainable and innovative “Wood Valley.”

Research limitations/implications

The key limitations are that the backcasting process has been conducted only through interviews and a participative approach with stakeholder dialogue is lacking in the process. This means that the desirable futures are created by the FBS companies only.

Originality/value

As a practical contribution, the study shows the future-oriented thinking and goals of FBS firms. As a theoretical contribution, it extends research on sustainable business models and discussions on the novel field of corporate foresight.
Innovation in public organizations: do government reforms matter?
Authors: Hijal-Moghrabi Imane , Sabharwal Meghna , Ramanathan Kannan
Published: September 2020

Purpose

The purpose of this study is to examine the impact of New Public Management (NPM) reforms/practices on innovation in public sector organizations. Although much is written on NPM, the assumption that NPM reforms stimulate organizational innovation has not been empirically tested. The present study is an attempt to bridge this research gap.

Design/methodology/approach

Building on open-systems approach, institutional theory, and innovation research, this study argues that organizational innovation occurs in response to stimuli in the external (environmental factors) and internal environment (organizational factors), considering NPM reforms/practices as a proxy for external or environmental factors. Organizational factors include formal structural complexity, senior management support and job security. The study tests this model using data from a national survey conducted in five states in the US.

Findings

The study provides empirical insights into our understanding of the factors that drive innovation in public sector organizations. The study finds that although environmental factors are as significant as organizational factors in driving innovation in the public sector, senior management support remains the most important predictor of innovation.

Originality/value

This paper fulfils an identified need to study the effect of NPM reforms and practices on innovation in public organizational settings.
Augmenting customer loyalty through customer experience management in the banking industry
Authors: Makudza Forbes
Published: September 2020

Purpose

The purpose of this paper is to analyse and evaluate the effect of customer experience management (virtual interaction, physical interaction and service interaction) on customer loyalty in the banking industry.

Design/methodology/approach

The study followed an explanatory research design to sample 384 respondents. Stepwise regression analysis was used to validate the relevance of the study model.

Findings

The results indicated that there is a positive association between customer experience management and customer loyalty. The dimensions of customer experience management, namely virtual interaction, physical interaction and service interaction, were also found to be statistically significant in explaining customer loyalty behaviour.

Practical implications

The study practically influences the way banks and other financial institutions gain competitive advantage through managing the experiences of customers in a volatile business environment. At a time when banks are no longer the only providers of financial services, the study offers a road map to reduce portfolio purchasing and switching behaviour through enhanced experience management at all customer touch points.

Originality/value

The study presents an augmented model of customer experience management which is linked to consumer loyalty.
Ethos at stake: roads to success among Chinese small businesses in Milan, Italy
Authors: Palombaro Ottavio
Published: September 2020

Purpose

This paper aims to check the presence of such relationship in the field. Certain values are at stake for the success of economic behavior. Since the genesis of modern capitalism, a set of beliefs proper of Calvinism (mainly Predestination but also Beruf, inner-worldly asceticism, role of Sects […] ) was said by Max Weber to cause an anxiety about salvation and generate a propensity to economic success as a sign of election. The author argues on the contrary that the Calvinist belief in the Perpetual Assurance of Salvation might cause a sense of self-efficacy able to favor economic success. To observe this in action today, it is crucial to consider the evolution that the Protestant ethic went through migrating first in North America and, finally, through the Protestant revival of China. Wenzhou is called “Jerusalem of China” for its large Protestant community that is also strongly involved in business. Some scholar already pointed out the presence among those entrepreneurs of this Protestant ethic (Yi Xiang, Boss-Christian […]).

Design/methodology/approach

The data presented in this comparative qualitative study pertain to ethnographic observations, job-shadowing and interviews done among Chinese Christian and non-Christian entrepreneurs from Wenzhou living in Milan, Italy.

Findings

The results show, with some adjustments, the presence of a Chinese version of the Protestant ethic overlapping with several values proper to the Chinese context (Confucianism, lineage, social network). The extension of the study to other cases must be done with caution considering the non-causal justificatory role of the belief.

Originality/value

Successful entrepreneurship involves specific social, cultural and even religious aspects that move beyond mere business strategies.
Brand equity and customer satisfaction: a comparative analysis of international and domestic tourists in Vietnam
Authors: Tran Phuong Kim Thi , Nguyen Vien Ky , Tran Vinh Trung
Published: September 2020

Purpose

This paper aims to examine the relationships between brand equity, customer satisfaction and cultural distance for a tourism destination. The mediating role of customer satisfaction and the moderating effect of cultural distance in these relationships are assessed.

Design/methodology/approach

The direct–indirect–moderating relationships were assessed by applying covariance-based SEM (CB-SEM), mediating and multi-group analysis. A paper survey was used to collect data from 618 tourists (domestic and international tourists) visiting a destination in Vietnam.

Findings

The findings support direct positive links between the dimensions of brand equity and customer satisfaction, except for the effect of destination brand awareness on destination brand loyalty. This work further demonstrates the mediating effect of customer satisfaction on the indirect relationships between the dimensions of brand equity. Cultural distance was found to moderate the connections between the research concepts.

Research limitations/implications

Future research should explore the model’s relationships based on comparisons in different destinations, to better understand the impact of cultural factors.

Originality/value

This study identifies specific factors to increase branding efficiency by developing and testing the relationship between brand equity and customer satisfaction. Using moderating variables through the lens of cultural distance, it proposes a mediated model. This work contributes to practice by informing destination managers on how to improve brand equity and satisfaction based on the cultural characteristics of international and domestic visitors.
Analysis of the current development of community centers in Jeddah city
Authors: Naji Ammar A. , Almaimani Ayad , Rahaman Khan Rubayet
Published: September 2020

Purpose

The Kingdom of Saudi Arabia (KSA) has been experiencing extensive development in the fields of architecture and planning in recent decades, which has included developing community centers in neighborhoods. These community centers have significant impacts on the social, cultural, recreational and economic lives of the inhabitants. The study has looked into the concept of modeled and non-modeled community centers among 114 neighborhoods. Moreover, the study aims to suggest that decision-makers should make efficient decisions to uphold amenities through the centers at the neighborhood level after considering the evaluation techniques included in this paper to ensure a sustainable urbanization.

Design/methodology/approach

The authors collected both qualitative and quantitative information through structured and un-structured interviews in the city of Jeddah. Afterward, the authors evaluated the centers with a summarized grading point based on qualitative judgments. Note that the online questionnaire survey was prepared to distribute in approximately 100 neighborhoods. However, 71 neighborhoods took part in the survey, with a total number of 402 responses. Moreover, the authors made a subjective evaluation of the studied neighborhoods to understand the quality of services offered by the community centers.

Findings

The obtained results reveal that the community centers in the city of Jeddah are playing important roles for socialization, allowing younger people to interact in a positive way, providing services to the communities and supporting volunteer work in and around the neighborhoods. Consequently, the research paper emphasizes the future needs of these important social infrastructures as part of a neighborhood design tool in the context of Jeddah city, KSA.

Originality/value

This research attempts to document the need for community centers in the city of Jeddah. Consequently, the study evaluates 26 different community centers to understand whether the improvements are required for supporting community activities. Indeed, few research works have made an effort to study community centers’ role in urban life in a unique geographic context. Through this research project, the authors have highlighted the implications of community centers in urban life in the city of Jeddah.
Towards sustainable commercial buildings: an analysis of operation and maintenance (O&M) costs in Sri Lanka
Authors: Weerasinghe Achini Shanika , Ramachandra Thanuja , Rotimi James O. B.
Published: September 2020

Purpose

Rising energy costs and increasing environmental concerns are catalysts for introducing sustainable design features in buildings. Incorporating sustainable design features in commercial buildings cannot be overstated because it could confer benefits to the investor (owners) and occupants. This study aims to develop a model that could aid in the prediction of operation and maintenance (O&M) costs from the knowledge of building-design variables. There is little evidence that design variables influence the O&M costs of buildings. Therefore, this study investigates the relationship between design variables and O&M costs in commercial buildings with the intent of developing a cost model for estimating O&M costs at the early design phase.

Design/methodology/approach

The study was approached quantitatively using a survey strategy. Data for the study were obtained from 30 randomly selected commercial buildings in the CBD in Colombo, Sri Lanka. Pareto's 80/20 rule, correlation and regression analysis were performed on the data to prove the statistical relationships between the buildings' O&M costs and their design variables.

Findings

The study found that 12 significant O&M costs elements contribute to about 82% of total O&M costs. Repairs and decoration had a strong correlation with building shape. Furthermore, the regression analysis found that O&M costs values were primarily dependent on the building size (the gross floor area and height of the buildings). The gross floor area and height handled over 73% of the variance in the O&M costs of commercial buildings in Sri Lanka.

Originality/value

These findings are a useful insight into the principles for design economies that could contribute to more sustainable commercial buildings.
Can risk prediction models help us individualise stillbirth prevention? A systematic review and critical appraisal of published risk models
Authors: Townsend R , Manji A , Allotey J , Heazell AEP , Jorgensen L , Magee LA , Mol BW , Snell KIE , Riley RD , Sandall J , Smith GCS , Patel M , Thilaganathan B , von Dadelszen P , Thangaratinam S , Khalil A
Published: September 2020

Background

Stillbirth prevention is an international priority – risk prediction models could individualise care and reduce unnecessary intervention, but their use requires evaluation.

Objectives

To identify risk prediction models for stillbirth, and assess their potential accuracy and clinical benefit in practice.

Search strategy

MEDLINE, Embase, DH‐DATA and AMED databases were searched from inception to June 2019 using terms relevant to stillbirth, perinatal mortality and prediction models. The search was compliant with Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines.

Selection criteria

Studies developing and/or validating prediction models for risk of stillbirth developed for application during pregnancy.

Data collection and analysis

Study screening and data extraction were conducted in duplicate, using the CHARMS checklist. Risk of bias was appraised using the PROBAST tool.

Results

The search identified 2751 citations. Fourteen studies reporting development of 69 models were included. Variables consistently included were: ethnicity, body mass index, uterine artery Doppler, pregnancy‐associated plasma protein and placental growth factor. For almost all models there were significant concerns about risk of bias. Apparent model performance (i.e. in the development dataset) was highest in models developed for use later in pregnancy and including maternal characteristics, and ultrasound and biochemical variables, but few were internally validated and none were externally validated.

Conclusions

Almost all models identified were at high risk of bias. There are first‐trimester models of possible clinical benefit in early risk stratification; these require validation and clinical evaluation. There were few later pregnancy models but, if validated, these could be most relevant to individualised discussions around timing of birth.

Tweetable abstract

Prediction models using maternal factors, blood tests and ultrasound could individualise stillbirth prevention, but existing models are at high risk of bias.
High infiltration of CD20+ B lymphocytes in extranodal natural killer/T‐cell lymphoma is associated with better prognosis
Authors: Chen Min‐Min , Zeng Guo‐Peng , Li Jing , Fu Jun‐Hong , Long Ya‐Yi , Pan Jie‐Ying , Wei Lin‐Zhi , Guan Jie‐Ying , Lin Ying‐Xi , You Hua , Si Cheng , Li Wen‐Xing , Liang Yi‐Jun , Liu Da‐Hai , Liu Fang , Liu Fang
Published: September 2020

Immune cells have an uncertain function during the progression of extranodal natural killer/T‐cell lymphoma (ENKTL). The present study determined the distribution, phenotype, and clinical significance of B lymphocytes in ENKTL. Immunohistochemistry indicated high infiltration of CD20+ B lymphocytes in the tumour tissues of 40% of the patients, and that a high infiltration correlated with better overall survival. Moreover, B lymphocytes had an active mature phenotype in situ and suppressed the proliferation of ENKTL cells in vitro. These results suggest that tumour infiltration of CD20+ B lymphocytes may be a new prognostic indicator for patients with ENKTL.
A phase 2, open‐label study of single‐dose dupilumab in children aged 6 months to <6 years with severe uncontrolled atopic dermatitis: pharmacokinetics, safety and efficacy
Authors: Paller A.S. , Siegfried E.C. , Simpson E.L. , Cork M.J. , Lockshin B. , Kosloski M.P. , Kamal M.A. , Davis J.D. , Sun X. , Pirozzi G. , Graham N.M.H. , Gadkari A. , Eckert L. , Ruddy M. , Bansal A.
Published: September 2020

Background

Dupilumab has demonstrated efficacy and acceptable safety in adults and children (aged 6–17 years) with moderate‐to‐severe atopic dermatitis (AD), but effective systemic therapy with a favorable risk–benefit profile in younger children remains a significant unmet need.

Objectives

To determine the pharmacokinetics, safety and efficacy of single‐dose dupilumab in children with severe AD aged ≥6 months to <6 years.

Methods

This open‐label, multicenter, phase 2, sequential, two‐age cohort, two‐dose level study (LIBERTY AD PRE‐SCHOOL; NCT03346434) included an initial cohort of older children aged ≥2 to <6 years, followed by a younger cohort aged ≥6 months to <2 years. Pharmacokinetic sampling, safety monitoring and efficacy assessments were performed during the 4‐week period after a single subcutaneous injection of dupilumab, in two sequential dosing groups (3 mg/kg, then 6 mg/kg). The use of standardized, low‐to‐medium potency topical corticosteroids was allowed.

Results

Forty patients were enrolled (20/age cohort, 10/dose level within a cohort) between December 20, 2017 and July 22, 2019. Within each age cohort, pharmacokinetic exposures after a single injection of dupilumab increased in a greater than dose‐proportional manner. At week 3, treatment with 3 and 6 mg/kg dupilumab reduced scores of mean Eczema Area and Severity Index by −44.6% and −49.7% (older cohort) and −42.7% and −38.8% (younger cohort), and mean Peak Pruritus NRS scores by −22.9% and −44.7% (older cohort) and −11.1% and −18.2% (younger cohort), respectively. At week 4, improvements in most efficacy outcomes diminished in both age groups, particularly with the lower dose. The safety profile was comparable to that seen in adults, adolescents and children.

Conclusions

Single‐dose dupilumab was generally well tolerated and substantially reduced clinical signs/symptoms of AD. Slightly better responses were seen in older than younger children. The pharmacokinetics of dupilumab were non‐linear, consistent with previous studies in adults and adolescents.
Signs of early cellular dysfunction in multiple system atrophy
Authors: Herrera‐Vaquero M. , Heras‐Garvin A. , Krismer F. , Deleanu R. , Boesch S. , Wenning G. K. , Stefanova N.
Published: September 2020

Aims

Multiple system atrophy (MSA) is a fatal neurodegenerative disease that belongs to the family of α‐synucleinopathies. At post mortem examination, intracellular inclusions of misfolded α‐synuclein are found in neurons and oligodendrocytes and are considered to play a significant role in the pathogenesis. However, the early steps of the disease process are unknown and difficult to study in tissue derived from end‐stage disease.

Methods

Induced pluripotent stem cells (iPSCs) were generated from patients’ and control skin fibroblasts and differentiated into NCAM‐positive neural progenitor cells (NPCs). The mitochondrial morphology and function were assessed by immunocytochemistry and high resolution respirometry. The ability to cope with exogenous oxidative stress was tested by exposure to different doses of luperox. The expression of α‐synuclein was studied by immunocytochemistry.

Results

We identified increased tubulation of mitochondria with preserved respiration profile in MSA‐derived NPCs. Exposure of these cells to exogenous oxidative stress even at low doses, triggered an excessive generation of reactive oxygen species (ROS) and cleavage of caspase‐3. MSA‐derived NPCs did not present changed levels of SNCA gene expression nor intracellular aggregates of α‐synuclein. However, we identified disease‐related translocation of α‐synuclein to the nucleus.

Conclusions

Our results show early cellular dysfunction in MSA‐derived NPCs. We identified changes in the redox homeostasis which are functionally compensated at baseline but cause increased susceptibility to exogenous oxidative stress. In addition, nuclear translocation of α‐synuclein in MSA‐derived NPCs supports an early cellular stress response which may precede the neurodegenerative process in this disorder.