bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic opioid treatment arrests neurodevelopment and alters synaptic activity in human midbrain organoids
Authors: Kim Hye Sung , Xiao Yang , Chen Xuejing , He Siyu , Im Jongwon , Willner Moshe J. , Finlayson Michael O. , Xu Cong , Zhu Huixiang , Choi Se Joon , Mosharov Eugene V. , Kim Hae-Won , Xu Bin , Leong Kam W.
Published: June 2021

The impact of long-term opioid exposure on the embryonic brain is crucial to healthcare due to the surging number of pregnant mothers with an opioid dependency. Current studies on the neuronal effects are limited due to human brain inaccessibility and cross-species differences among animal models. Here, we report a model to assess cell-type specific responses to acute and chronic fentanyl treatment, as well as fentanyl withdrawal, using human induced pluripotent stem cell (hiPSC)-derived midbrain organoids. Single cell mRNA sequencing (25,510 single cells in total) results suggest that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters the pathways associated with synaptic activities and neuron projection. Acute fentanyl treatment, however, increases dopamine release but does not induce significant changes in gene expressions of cell lineage development. To date, our study is the first unbiased examination of midbrain transcriptomics with synthetic opioid treatment at the single cell level.
A homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium
Authors: Van Winkle Jacob A. , Peterson Stefan T. , Kennedy Elizabeth A. , Wheadon Michael J. , Ingle Harshad , Desai Chandni , Rodgers Rachel , Constant David A. , Wright Austin P. , Li Lena , Artyomov Maxim , Lee Sanghyun , Baldridge Megan T. , Nice Timothy J.
Published: June 2021

Interferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine of specific pathogen-free mice. This homeostatic ISG expression is restricted to IECs, depends on IEC-intrinsic expression of IFN-λ receptor (Ifnlr1), and is associated with IFN-λ production by leukocytes. Strikingly, imaging of these homeostatic ISGs reveals localization to pockets of the epithelium and concentration in mature IECs. Correspondingly, a minority of mature IECs express these ISGs in public single-cell RNA sequencing datasets from mice and humans. Furthermore, we assessed the ability of orally-administered bacterial components to restore localized ISGs in mice lacking bacterial microbiota. Lastly, we find that IECs lacking Ifnlr1 are hyper-susceptible to initiation of murine rotavirus infection. These observations indicate that bacterial microbiota stimulate ISGs in localized regions of the intestinal epithelium at homeostasis, thereby preemptively activating antiviral defenses in vulnerable IECs to improve host defense against enteric viruses.
Heavy-tailed distributions in a stochastic gene autoregulation model
Authors: Bokes Pavol
Published: June 2021

Synthesis of gene products in bursts of multiple molecular copies is an important source of gene expression variability. This paper studies large deviations in a Markovian drift–jump process that combines exponentially distributed bursts with deterministic degradation. Large deviations occur as a cumulative effect of many bursts (as in diffusion) or, if the model includes negative feedback in burst size, in a single big jump. The latter possibility requires a modification in the WKB solution in the tail region. The main result of the paper is the construction, via a modified WKB scheme, of matched asymptotic approximations to the stationary distribution of the drift–jump process. The stationary distribution possesses a heavier tail than predicted by a routine application of the scheme.

MSC 2020

92C40; 60J76, 45D05, 41A60
Zebrafish Danio rerio trunk muscle structure and growth from a spatial transcriptomics perspective
Authors: Liu Guanting , Ito Takumi , Kijima Yusuke , Yoshitake Kazutoshi , Asakawa Shuichi , Watabe Shugo , Kinoshita Shigeharu
Published: June 2021

Compared to mammals, some fish exhibit indeterminate growth characteristics, meaning they can continue growing throughout their lives. Zebrafish trunk skeletal muscle can in general be classified into slow, intermediate, and fast based on morphological and physiological characteristics. After hatching, hyperplasia can be observed in the muscles of juvenile zebrafish, and with growth, hyperplasia in the fast muscles gradually decreases until it stagnates, after which fast muscle development relies on hypertrophy. In slow muscle, hyperplasia continues throughout life. Teleost muscle structure and growth has been described mainly by morphological and physiological features based on the expression of a limited number of proteins, transcripts, and metabolites. The details of mechanism remain unclear. Visium Spatial Gene Expression solution was used in this study. On the adult slide, 10 clusters were obtained based on whole gene expression similarities. The spatial expression of myosin heave chains, myosin light chains and myosin-binding proteins was investigated. GO enrichment analysis was also performed on different muscle regions of aged zebrafish. Dorsal and ventral slow muscles share the same processes such as myofibril assembly and muscle tissue development. On the larvae slide, 3 clusters were obtained, GO enrichment analysis suggest active muscle formation in zebrafish larvae.
Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age
Authors: Dimitrova Ralica , Pietsch Maximilian , Ciarrusta Judit , Fitzgibbon Sean P. , Williams Logan Z. J. , Christiaens Daan , Cordero-Grande Lucilio , Batalle Dafnis , Makropoulos Antonios , Schuh Andreas , Price Anthony N. , Hutter Jana , Teixeira Rui PAG , Hughes Emer , Chew Andrew , Falconer Shona , Carney Olivia , Egloff Alexia , Tournier J-Donald , McAlonan Grainne , Rutherford Mary A. , Counsell Serena J. , Robinson Emma C. , Hajnal Joseph V. , Rueckert Daniel , Edwards A. David , O’Muircheartaigh Jonathan
Published: June 2021

Introduction

The dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors.

Methods

We sought to first map typical cortical micro and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n=270). Then we offer a comprehensive characterisation of the cortical consequences of preterm birth in 78 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months.

Results

In the term-born neonatal brain, we observed regionally specific age-associated changes in cortical morphology and microstructure, including rapid surface expansion, cortical thickness increase, reduction in cortical anisotropy and increase in neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months.

Conclusion

We showed that preterm birth alters cortical micro and macrostructural maturation near the time of fullterm birth. Deviations from normative development were highly variable between individual preterm infants.
The vagus nerve is critical for regulation of hypothalamic-pituitary-adrenal axis responses to acute stress
Authors: Keller Bailey N. , Snyder Angela E. , Coker Caitlin R. , Aguilar Elizabeth A. , O’Brien Mary K. , Bingaman Sarah S. , Arnold Amy C. , Hajnal Andras , Silberman Yuval
Published: June 2021

The hypothalamic pituitary adrenal (HPA) axis is a critical regulator of physiologic and psychological responses to acute and chronic stressors. HPA axis function is control by numerous feedback inhibitory mechanisms, disruptions of which can lead to various psychiatric conditions, such as depression, posttraumatic stress disorder, and schizophrenia. Vagus nerve stimulation has been shown to be efficacious in the treatment of in these various mental health issues potentially via modulation of HPA axis function, but the mechanisms by which the vagus nerve may regulate HPA function has not been fully elucidated. In the present studies, we sought to test the hypothesis that the vagus nerve is a critical regulator of HPA function. Neuroendocrine function and neurocircuit changes in corticotropin releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus (PVN) were examined following acute stress after subdiaphragmatic left vagotomy (VX) in adult male Sprague-Dawley rats. We found that VX mimics HPA activation seen in sham surgery animals exposed to acute restraint stress, particularly increased plasma corticosterone levels, elevated PVN CRF mRNA, and increased action potential firing of putative CRF neurons in PVN brain slices. Furthermore, VX animals exposed to acute restraint stress showed increased elevations of plasma corticosterone and PVN CRF mRNA which may be due to lack of compensatory PVN GABAergic signaling in response to acute stress. Both Sham/Stress and VX/no stress conditions increased action potential firing in putative PVN CRF neurons, but this effect was not seen in the VX/stress condition, suggesting that not all forms of stress compensation are lost following VX. Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of local PVN neurocircuit activity.
M1-linked ubiquitination facilitates NF-κB activation during sterile inflammation
Authors: Aalto Anna , Martínez-Chacón Gabriela , Tsyganova Nadezhda , Kreutzer Joose , Kallio Pasi , Broemer Meike , Meinander Annika
Published: June 2021

Methionine 1 (M1)-linked ubiquitination plays a key role in the regulation of inflammatory nuclear factor-κB (NF-κB) signalling and is important for clearance of pathogen infection in Drosophila melanogaster. M1-linked ubiquitin (M1-Ub) chains are assembled by the linear ubiquitin E3 ligase (LUBEL) in flies. Here, we have studied the role of LUBEL in sterile inflammation induced by different types of cellular stresses. We have found that LUBEL catalyses formation of M1-Ub chains in response to hypoxic, oxidative and mechanical stress conditions. LUBEL is shown to be important for flies to survive low oxygen conditions and paraquat-induced oxidative stress. This protective action seems to be driven by stress-induced activation of the NF-κB transcription factor Relish via the Immune deficiency (Imd) pathway. In addition to LUBEL, the intracellular mediators of Relish activation, including the Drosophila inhibitor of apoptosis (IAP) Diap2, the IκB kinase γ (IKKγ) Kenny and the initiator caspase Death-related ced-3/Nedd2-like protein (Dredd), but not the membrane receptor peptidoglycan recognition protein (PGRP)-LC, are shown to be required for sterile inflammatory response and survival. Finally, we showed that the stress-induced upregulation of M1-Ub chains in response to hypoxia, oxidative and mechanical stress is also induced in mammalian cells. Taken together, our results suggest that M1-Ub chains are important for NF-κB signalling in inflammation induced by stress conditions often observed in chronic inflammatory diseases and cancer.
Polymerase theta-helicase promotes end joining by stripping single-stranded DNA-binding proteins and bridging DNA ends
Authors: Schaub Jeffrey M. , Soniat Michael M. , Finkelstein Ilya J.
Published: June 2021

Homologous recombination-deficient cancers rely on DNA polymerase Theta (Polθ)-Mediated End Joining (TMEJ), an alternative double-strand break repair pathway. Polθ is the only vertebrate polymerase that encodes an N-terminal superfamily 2 (SF2) helicase domain, but the role of this helicase domain in TMEJ remains unclear. Using single-molecule imaging, we demonstrate that Polθ-helicase (Polθ-h) is a highly processive single-stranded DNA (ssDNA) motor protein that can efficiently strip Replication Protein A (RPA) from ssDNA. Polθ-h also has a limited capacity for disassembling RAD51 filaments but is not processive on doublestranded DNA. Polθ-h can bridge two non-complementary DNA strands in trans. PARylation of Polθ-h by PARP-1 resolves these DNA bridges. We conclude that Polθ-h removes RPA and RAD51 filaments and mediates bridging of DNA overhangs to aid in polymerization by the Polθ polymerase domain.
Single nuclei transcriptome of the Lesser Duckweed Lemna minuta reveals cell trajectories for an entire plant
Authors: Abramson Bradley W. , Novotny Mark , Hartwick Nolan T. , Colt Kelly , Aevermann Brian D. , Scheuermann Richard H. , Michael Todd P.
Published: June 2021

The ability to trace every cell in some model organisms has led to the fundamental understanding of development and cellular function. However, in plants the complexity of cell number, organ size and developmental times makes this a challenge even in the diminutive model plant Arabidopsis thaliana. Here we develop the Lesser Duckweed Lemna minuta as a model with a reduced body plan, small genome size and clonal growth pattern that enables simultaneous tracing of cells from the entire plant over the complete developmental cycle. We generated a chromosome-resolved genome for the 360 megabase genome and defined the growth trajectory of the entire plant with single nuclei RNA sequencing. The L. minuta gene complement represents a primarily non-redundant set with only the ancient tau whole genome duplication shared with all monocots, and paralog expansion as a result of tandem duplications related to phytoremediation. Thirteen distinct cell types representing meristem, the leaf-stem fusion called a frond, and root-like tissues were defined using gene orthology with single cell expression from model plants, gene ontology categories, and cell trajectory analysis. Dividing meristem cells give rise to two main branches of root-transition and mesophyll cells, which then give rise to terminally differentiated parenchyma, epidermal and root cells. Mesophyll tissues express high levels of elemental transport genes consistent with this tissue playing a role in L. minuta wastewater detoxification. The L. minuta genome and cell map provide a paradigm to decipher developmental genes and pathways for an entire plant.

Sentence summary

Genome and single nuclei transcriptome of the Lesser Duckweed Lemna minuta enables tracing of all developmental, transitional and terminal cells of an entire plant.
Usefulness of the budget: the mediating effect of participative budgeting and budget-based evaluation and rewarding
Authors: Wagner Jaroslav , Petera Petr , Popesko Boris , Novák Petr , Šafr Karel
Published: June 2021

Purpose

This paper contributes to budgeting-related literature by investigating whether the participation of operational managers in budgeting, and budget-based evaluations and the rewarding of operational managers, significantly mediate the relationship between budget use for operational management and the perceived usefulness of the budget.

Design/methodology/approach

The paper is based on data gathered from a survey of Czech medium- and large-sized companies from the manufacturing sector. The hypothesised relationships are tested using partial least squares structural equation modelling (PLS-SEM).

Findings

Overall usefulness of the budget, as perceived by principals (top managers), is positively influenced by the scope of budget use, but, more importantly, the positive mediating effects of participative budgeting and budget-based evaluation and rewarding on this relationship are significant and strong.

Research limitations/implications

The subjective perceptions of respondents were investigated with the understanding that they may not represent actual situations in their organisations. Companies with well-functioning budgeting systems were more likely to take part in the research. Regarding satisfaction, the authors studied the perceived usefulness of the budget. Only medium- and large-sized manufacturing companies located in a post-communist country were analysed and generalisations should, therefore, be taken with caution.

Practical implications

The results in the studied sample indicate that satisfaction with budgeting is positively correlated with the rewarding and evaluation of operational managers, and with enabling the participation of operational managers in preparing and updating their budgets.

Originality/value

This research contributes to prior literature on budgeting by investigating the mediating effects of the participation of operational managers in budgeting, and the budget-based evaluation and rewarding of operational managers on the perceived usefulness of the budget by principals in an integrated model using the PLS-SEM approach.
How do subordinates react to perceived narcissistic supervision? The roles of perceived interactional justice and need for belonging
Authors: Ni Dan , Liu Xin , Zheng Xiaoming
Published: June 2021

Purpose

This paper aims to examine how and when perceived narcissistic supervision influences subordinates' work engagement and counterproductive work behavior (CWB) based on organizational justice theory.

Design/methodology/approach

Two-wave data were collected from 320 employees in a Chinese manufacturing company.

Findings

Subordinates' perceived interactional justice mediated the relationships between perceived narcissistic supervision and work engagement and CWB. Higher levels of subordinates' need for belonging strengthened the detrimental impacts of perceived narcissistic supervision on subordinates' outcomes.

Practical implications

Organizations should reduce the occurrence of narcissistic supervision, enhance subordinates' perception of interactional justice and pay more attention to subordinates' need for belonging in personnel and team arrangement.

Originality/value

Although research has documented the detrimental effects of perceived narcissistic supervision, little effort has been made to investigate how such effects occur and which factors might amplify such effects. This study identified the mechanism underlying the link between perceived narcissistic supervision and subordinates' outcomes and unpacked the moderating role of subordinates' need for belonging.
Praised from birth: social approval assets in the creation of a new university
Authors: Aula Hannamari , Siltaoja Marjo
Published: June 2021

Purpose

The authors explore how social approval assets, namely status and reputation, are used to legitimate and categorise a new national university. They argue that in the course of the legitimation process, status and reputation work as stakeholder-oriented value-creating benefits. The authors specifically analyse the discursive constructions and labels used in the process and how the process enables nationwide university reform.

Design/methodology/approach

The authors’ longitudinal case study utilises critical discourse analysis and analyses media and policy discourses regarding the birth of Aalto University.

Findings

The findings suggest that the legitimation of the new university was accomplished through the use of two distinct discourses: one on higher education and another on the market economy. These discourses not only sought to legitimise the new university as categorically different from existing Finnish universities, but also rationalised the merger using the expected reputation and status benefits that were claimed would accrue for supporters.

Practical implications

This study elaborates on the role of various social approval assets and labels in legitimation processes and explores how policy enforcement can take place in arenas that are not necessarily perceived as policymaking. For managers, it is crucial to understand how a chosen label (name) can result in both stakeholder support and resistance, and how important it is to anticipate the changes a label can invoke.

Originality/value

The authors propose that the use of several labels regarding a new organisation is strategically beneficial to attracting multiple audiences who may hold conflicting interests in terms of what the organisation and its offerings should embody. They propose that even though status and reputation have traditionally been defined as possessions of an organisation, they should be further understood as concepts used to disseminate and justify the interests, norms, structures and values in a stakeholder network.
Mixed qualitative–quantitative approach for bidding decisions in construction
Authors: Mohamed Emad , Jafari Parinaz , Hammad Ahmed
Published: June 2021

Purpose

The bid/no-bid decision is critical to the success of construction contractors. The factors affecting the bid/no-bid decision are either qualitative or quantitative. Previous studies on modeling the bidding decision have not extensively focused on distinguishing qualitative and quantitative factors. Thus, the purpose of this paper is to improve the bidding decision in construction projects by developing tools that consider both qualitative and quantitative factors affecting the bidding decision.

Design/methodology/approach

This study proposes a mixed qualitative-quantitative approach to deal with both qualitative and quantitative factors. The mixed qualitative-quantitative approach is developed by combining a rule-based expert system and fuzzy-based expert system. The rule-based expert system is used to evaluate the project based on qualitative factors and the fuzzy expert system is used to evaluate the project based on the quantitative factors in order to reach the comprehensive bid/no-bid decision.

Findings

Three real bidding projects are used to investigate the applicability and functionality of the proposed mixed approach and are tested with experts of a construction company in Alberta, Canada. The results demonstrate that the mixed approach provides a more reliable, accurate and practical tool that can assist decision-makers involved in the bid/no-bid decision.

Originality/value

This study contributes theoretically to the body of knowledge by (1) proposing a novel approach capable of modeling all types of factors (either qualitative or quantitative) affecting the bidding decision, and (2) providing means to acquire, store and reuse expert knowledge. Practical contribution of this paper is to provide decision-makers with a comprehensive model that mimics the decision-making process and stores experts' knowledge in the form of rules. Therefore, the model reduces the administrative burden on the decision-makers, saves time and effort and reduces bias and human errors during the bidding process.
Comparative analysis of the relationship between internal control weakness and different types of auditor opinions in fraudulent and non-fraudulent firms
Authors: Lari Dashtbayaz Mahmoud , Salehi Mahdi , Hedayatzadeh Mahdi
Published: June 2021

Purpose

This study aims to assess the relationship between internal control weakness and different types of auditor opinions in fraudulent and non-fraudulent firms. The study's main objective is to investigate fraud in business firms and analyze internal controls and types of proposed opinions by the auditor about his desired firm. The outbreak of fraud in firms is of utmost importance to a broad spectrum of society. Internal controls and the auditor's role in preventing and detecting frauds should not be taken for granted.

Design/methodology/approach

The present study's statistical population includes 179 listed firms on the Stock Exchange selected as the study sample using the systematic elimination method during 2012–2019. As the study's dependent variable (the type of auditor’s opinion), research hypotheses were analyzed using the Logit regression model.

Findings

The results show that the relationship between internal control weakness and opinion type is significantly different in fraudulent and non-fraudulent firms. Moreover, the relationship between internal control weakness and type of auditor opinion in fraudulent firms and the relationship between internal control weakness and type of auditor opinion in non-fraudulent firms are significant.

Originality/value

By assessing the related literature, the authors have found no study to directly assess the comparative relationship between internal control weakness and the type of auditor opinion, which can be named as the main objective of the study.
Sustainable management of agriculture products value chain in responses to climate change for South-Eastern coast of Bangladesh
Authors: Barua Prabal , Rahman Syed Hafizur , Barua Maitri
Published: June 2021

Purpose

This paper is designed to assess the sustainable value chain approaches for marketing channel development opportunities for agricultural products in coastal Bangladesh to combat climate change through an approach of community-based adaptation options.

Design/methodology/approach

The study was designed to select the potential value chain candidate and to analyze and establish a value chain map to benefit the crop farmers. In this connection, the resources of the whole context were evaluated. The approach uses few tools to generate three outputs, the last of which are the final list of value chains selected for in-depth assessment to design interventions as community-based adaptation practices of the study to combat climate change in the study areas.

Findings

The study demonstrated that the difference in the institutional circumstances of the end markets of the agriculture products is connected to the different categories of harmonization and control of the facilitating environment throughout the supply chains. National and local networks improve the value chain in terms of the value addition of the agriculture products, technology improvement, market access and profitability of the products. Strengthening the weak financial structure, focus more on formal financial systems and resolving sociocultural and climate change-induced hazard concerns are the major concerns on the development of value chains in the countries. Apparently, guarantee for good governance, checking illegal and unregulated market contexts, proper mitigation measures to climate change are some paramount important issues for the sustainable management of livelihood, yield, income and development.

Practical implications

All kinds of stakeholders of the agriculture product value chain should focus on competitiveness and productivity and look for and exploit multiple ways to add value once initial success has been attained with a single deal. Ensuring sustainability within the value chains is an important feature to cater to the challenges and changing demands of the age.

Originality/value

The study will help to established a sustainable value chain approach in response to climate change, which process will help to existent opportunities for firms to manage the issue of climate risk by codeveloping and employing adaptation options that may be more preferred or accepted by consumers across the entire chain for the sustainable management of livelihood, yield, income and development.
Why this realtor®? Branding at Boyes Group Realty Inc. version: 2020-10-07
Authors: Klassen Brooke , Lane Brian
Published: June 2021

Theoretical basis

The case learning objectives and discussion questions relate very closely to several theories related to branding, including brand positioning, brand growth, brand management, customer value proposition, brand matrix and brand identity.

Research methodology

The information provided in this case was gathered by the author through personal interviews and email exchanges with Jordan Boyes, managing broker and owner of Boyes Group Realty Inc. Secondary research was also conducted to gather relevant academic materials, as well as industry and competitor information.

Case overview/synopsis

Jordan Boyes opened Boyes Group Realty Inc. in 2015 after working as a Realtor® at another private realty firm in Saskatoon, Saskatchewan for several years. They offered buying and selling services in the areas of commercial, residential and farm real estate. Over the past five years, they had experienced strong sales numbers and growth in the number of new agents joining the company. However, Boyes saw untapped potential in the marketplace and wanted to develop a brand strategy that took the best advantage of brand extension opportunities to drive the continued growth of his company.

Complexity academic level

This case is suitable at the undergraduate level for a branding course, marketing strategy course or services marketing course. The case is best used to apply the concept of developing brand identity and making strategic decisions in a service-based organization.
Tourism as a bridge for inter-cultural understanding and reconciliation despite the COVID-19 challenges: an interview with Dr Itsik Peres
Authors: Altshuler Alex
Published: June 2021

Purpose

The interview with Mr Itsik (Isaac) Peres aims to provide a set of insights from the field – through global, Middle-Eastern and Israeli lenses – on some of the major challenges for the tourism industry in the face of COVID-19.

Design/methodology/approach

This paper consists of an academic interview with Mr Itsik (Isaac) Peres and presents an engaging discussion between the experienced and knowledgeable tour guide and a scholar of resilience.

Findings

Mr Peres calls for a balanced approach that views health considerations as the top priority but at the same time believes that the tourism industry may – at least partially – adapt itself to the global pandemic and operate through a “new normal” during COVID-19. It is also claimed that there is no conflict between necessary international standards and local knowledge, creativity and adaptation measures. Mr Itsik Peres also addresses the potential major local and regional opportunities for the tourism industry and for the society as a whole that may emerge because of the new Abraham Accords (a peace treaty between Israel, United Arab Emirates and Bahrain signed in August 2020).

Originality/value

This paper presents an original and comprehensive analysis of the major challenges and solutions for the tourism industry in the face of COVID-19 through the lenses of an experienced professional in the field. The interview provides the reader with short-term and long-term “take away” messages for more effective and adaptive functioning of the tourism industry – during the COVID-19 epidemic and following its hopeful end.
Experimental evaluation of herbicide use on biodiversity, ecosystem services and timber production trade‐offs in forest plantations
Authors: Stokely Thomas D. , Kormann Urs G. , Verschuyl Jake , Kroll Andrew J. , Frey David W. , Harris Scott H. , Mainwaring Doug , Maguire Doug , Hatten Jeff A. , Rivers James W. , Fitzgerald Stephen , Betts Matthew G.
Published: June 2021

The value of non‐commodity ecosystem services provided by forests is widely recognized, but intensive forest management practices are increasing, with uncertain consequences for a multitude of these services. Quantitative relationships among biodiversity conservation, timber production and other ecosystem services remain poorly understood, especially during the early‐successional period of intensively managed forestlands.

We manipulated management intensity in regenerating forest plantations to test the prediction that treatments aimed at maximizing timber production decrease biodiversity conservation and non‐timber services. We measured species richness of 3 taxonomic groups and 13 proxies for provisioning, cultural and regulating services within stands randomly assigned to one of the three herbicide application intensities or an untreated control.

Herbicides increased allocation of net primary production to crop trees, increasing projected timber volume and revenues at 40‐ and 60‐year harvest ages. Commonly used herbicide prescriptions reduced culturally valued plants by 71%, wild‐ungulate forage by 41%, avian richness by 20% and pollinator floral resources by 42%, the latter being associated with 38% fewer pollinator species. However, agriculturally valued bumblebees, pollination of blueberries, avian‐mediated arthropod control, wild ungulate observations and regulation services tied to forest productivity appeared unaffected by increasing management intensity and timber production.

Species richness and flora‐provided services in young forest plantations exhibited strong trade‐offs with projected timber production, whereas post‐treatment vegetation regeneration and site‐level variation likely maintained a range of other services. Although vegetation recovery is important for supporting wildlife and some ecosystem services on industrial forestlands, it is unlikely that any single prescription can optimize both timber and non‐timber benefits to society across managed forest landscapes. Instead, producing different services in discrete portions of the landscape may be necessary.

Synthesis and applications. We tested the effects of intensive forest management via herbicides on ecosystem services and found that biodiversity responses and services from early‐successional vegetation trade‐off against timber production. A number of services appeared to be compatible with timber production, although no single prescription optimized the full range of services. Stand‐level biodiversity conservation and a variety of services could potentially be provided by treatment skips and less‐intensive management on productive sites, although it is unlikely that all services can be optimized without landscape‐level planning.
Rosuvastatin and low‐dose carvedilol combination protects against isoprenaline‐induced myocardial infarction in rats: Role of PI3K/Akt/Nrf2/HO‐1 signalling
Authors: Baraka Sarah A. , Tolba Mai F. , Elsherbini Doaa A. , El‐Naga Reem N. , Awad Azza S. , El‐Demerdash Ebtehal
Published: June 2021

Rosuvastatin has been shown to activate PI3K/Akt/Nrf2/HO‐1 pathway, which promotes cell survival in the myocardium. This study investigated the therapeutic benefit of adding rosuvastatin to low‐dose carvedilol in protection against myocardial infarction (MI). Rosuvastatin (RSV) and carvedilol (CAR) were given for 7 consecutive days with concurrent administration of two doses of isoprenaline (ISP) on 6th and 7th days to induce MI. Isoprenaline injections caused detrimental alterations in the myocardial architecture and electrocardiogram (ECG) pattern and significantly increased the infarct size, heart index and serum levels of cardiotoxicity markers compared to the control group. ISP induced oxidative damage, inflammatory and apoptotic events and downregulated PI3K/Akt/Nrf2/HO‐1 signalling pathway compared to the control values. Treatment with low‐dose CAR and/or RSV prevented the ECG and histopathological alterations induced by ISP, and also reduced the infarct size, heart index, serum creatine kinase‐MB, cardiac troponin‐I and C‐reactive protein levels compared to ISP group. CAR and/or RSV treatment restored the activity of superoxide dismutase and total antioxidant capacity with a consequent reduction in lipid peroxides level. Further, they decreased the expression of nuclear factor (NF)‐κB (p65) and increased the phosphorylated PI3K and Akt, which may activate the anti‐apoptotic signalling as evidenced by the decreased active caspase 3 level. The combination therapy has a more significant effect in the most studied parameters than their monotherapy, which may be because of the activation of PI3K/Akt Nrf2/HO‐1 pro‐survival signalling pathway. This study highlights the potential benefits of combining RSV with low‐dose CAR in case of MI.
Metabolic potentials of members of the class Acidobacteriia in metal‐contaminated soils revealed by metagenomic analysis
Authors: Xu Rui , Sun Xiaoxu , Häggblom Max M. , Dong Yiran , Zhang Miaomiao , Yang Zhaohui , Xiao Enzong , Xiao Tangfu , Gao Pin , Li Baoqin , Sun Weimin
Published: June 2021

The relative abundance of Acidobacteriia correlated positively with the concentrations of arsenic (As), mercury (Hg), chromium (Cr), copper (Cu) and other metals, suggesting their adaptation of the metal‐rich environments. Metagenomic binning reconstructed 29 high‐quality metagenome‐assembled genomes (MAGs) associated with Acidobacteriia, providing an opportunity to study their metabolic potentials. These MAGs contained genes to transform As, Hg and Cr through oxidation, reduction, efflux and demethylation, suggesting the potential of Acidobacteriia to transform such metal(loid)s. Additionally, genes associated with alleviation of acidic and metal stress were also detected in these MAGs. Acidobacteriia may have the capabilities to resist or transform metal(loid)s in acidic metal‐contaminated sites. Moreover, these genes encoding metal transformation could be also identified in the Acidobacteriia‐associated MAGs from five additional metal‐contaminated sites across Southwest China, as well as Acidobacteriia‐associated reference genomes from the NCBI database, suggesting that the capability of metal transformation may be widespread among Acidobacteriia members. This discovery provides an understanding of metabolic potentials of the Acidobacteriia in acidic metal‐rich sites.
Does Government Ideology Affect the Relationship Between Government Spending and Economic Growth?
Authors: Haini Hazwan , Wei Loon Pang
Published: June 2021

This study examines whether government ideology affects the relationship between government spending and economic growth in eighty eight countries from 1975 to 2017 using dynamic panel estimators. Previous studies have overlooked the role of government ideology, which can influence economic policies such as government spending. The results show that government spending is negative and significant to economic growth, while left‐wing governments are associated with economic growth. However, when moderating for government ideology, the findings show that the marginal effect of government spending is positive for right‐wing governments, while the marginal impact of government spending is negative for left‐wing governments. The results imply that government spending policies must be aligned with the respective government ideology in order to benefit from further economic growth. Policy implications are discussed.
Dual‐fluorescence imaging and automated trophallaxis detection for studying multi‐nutrient regulation in superorganisms
Authors: Baltiansky Lior , Sarafian‐Tamam Einav , Greenwald Efrat , Feinerman Ofer
Published: June 2021

Much like a single organism, colonies of social insects regulate their collective nutrition towards a specific intake of nutrients. Yet, the mechanisms behind this colony‐level regulation are not fully understood. Although foraging behaviour in social insects has been studied extensively, not much is known on its relation with feeding processes that occur within the nest. In the nest, food is commonly transferred between individuals in numerous oral feeding interactions (trophallaxis). Studies on the properties of these trophallactic networks have so far been limited by: (a) the difficulty to non‐intrusively measure food inside individual ants, let alone its nutritional composition, and (b) the meticulous manual labour involved in detecting trophallactic events.

Our dual‐fluorescence imaging set‐up is designed to track two food sources, each labelled with a different fluorophore, as they are disseminated throughout a freely behaving colony of individually tagged ants. Additionally, our image‐based deep learning algorithm for automatic detection of ant trophallaxis events efficiently yields a detailed record of all food‐transfer interactions.

Using a series of calibration experiments, we demonstrate the reliability of our measurements. We then exemplify the capabilities of our new method by tracking food dissemination in a colony of Camponotus sanctus ants supplied with two nutritionally distinct food sources. We follow the amount of each food type in the crop of each ant in the colony. Our data reveal the path in nutrient space that the colony took to reach its final nutrient intake, the contributions of the different forager ants to this path and the dynamic nutritional states of all ants in the colony. We further demonstrate the potential applicability of dual‐fluorescence food imaging to other insect species.

Our system provides access to data that were previously unavailable and is crucial for a complete description of nutrient regulation by social insects. More broadly, the ability to simultaneously and efficiently track two material flows in a behaving colony provides new opportunities for tackling many open and emerging questions on topics other than nutrition, such as disease spread and social regulation of colony development.
Dioscin elevates lncRNA MANTIS in therapeutic angiogenesis for heart diseases
Authors: Kong Chuiyu , Lyu Dayin , He Chang , Li Rui , Lu Qiulun
Published: June 2021

Dioscin has been widely used in clinics for coronary artery disease (CAD) treatment for years in China. However, the underlying mechanism for Dioscin‐mediated cardioprotective effect has not been elucidated. Here, we showed that Dioscin significantly rescues the cardiac function in mouse model of myocardial infarction (MI), accompanied by the reduction of cardiac fibrosis and apoptosis, resulting from elevated angiogenesis. Mechanistically, Dioscin promotes the proliferation and migration of hypoxic endothelial cells via the up‐regulation of lncRNA MANTIS, which serves as a scaffolding lncRNA within a chromatin remodeling complex. Meanwhile, it enables pol II binding to the transcription start sites, which leads to induced expression of angiogenesis‐related genes, including SOX18, SMAD6, and COUP‐TFII. Conversely, IncRNA MANTIS silencing prevents Dioscin‐induced migration and angiogenesis in hypoxic endothelial cells. Taken together, these data provide new insights that clarifies the cardioprotective effects of Dioscin against myocardial infarcted injury and confirms the effect on angiogenic activity of endothelial cells. This will build a solid theoretical basis for clinical therapeutic strategies.
Guideline adherence and clinical relevance of laboratory investigations during follow‐up in paediatric coeliac disease: A Dutch single‐centre cohort study
Authors: van Kalleveen Michael W. , Dykstra Tim C. , de Meij Tim G. J. , Plötz Frans B.
Published: June 2021

Aim

Dutch national guidelines on follow‐up of paediatric celiac disease (CD) are available. The primary aim was to evaluate guideline adherence by paediatricians during follow‐up. The secondary aim was to determine the clinical relevance and diagnostic yield of routine laboratory tests suggested by these guidelines.

Methods

A retrospective, single‐centre, cohort study was performed in paediatric CD patients who visited Tergooi Hospital, the Netherlands, between January 2017 and December 2019, with follow‐up of at least twelve months after diagnosis. We analysed guideline adherence, number of outpatient visits and all laboratory data.

Results

We included 91 CD children with a median follow‐up of 4.0 years (range 1–16 years) and 162 follow‐up visits. Strict adherence amongst paediatricians during follow‐up was 8.0% (13/162 cases). A total of 1570 laboratory tests were performed of which 45.4% (713/1570) was in strict compliance with the Dutch national guidelines. Clinically relevant deviations were observed in 5.3% of requested laboratory tests.

Conclusion

Strict guideless adherence amongst paediatricians in follow‐up of paediatric CD was low and the clinical relevance of the suggested routine laboratory tests is limited. This underlines the increasing notion that evidence‐based guidelines on follow‐up of CD are warranted.
Dual commitment profiles and job satisfaction among temporary agency workers
Authors: Menatta Pietro , Consiglio Chiara , Borgogni Laura , Moschera Luigi
Published: June 2021

Temporary agency workers (TAWs) are an ever‐increasing type of employees which establish a double work relationship with both the agency and the client organization. Within this context, the concept of dual commitment has received considerable attention in the last years. The present contribution integrates dual commitment line of research with the one adopting a person‐centered approach to the study of commitment configurations, to investigate commitment profiles on a large sample of TAWs. According to Sinclair et al.'s framework, we aimed to identify TAWs' commitment profiles based on their levels of dual affective commitment (to the agency and to the client organization) and on their general continuance commitment and to investigate differences in job satisfaction among profiles. Latent profile analyses on 7225 TAWs revealed 5 distinct profiles, namely Dually Free Agents, Dually Involved, Dually Allied, (Unilaterally) Client Allied and (Unilaterally) Agency Invested. The Dually Involved profile, followed by the Dually Allied profile, had the highest level of job satisfaction, whereas the Dually Free Agent profile and the (Unilaterally) Agency Invested had the lowest. Furthermore, the (Unilaterally) Client Allied group had a higher level of job satisfaction as compared to the (Unilaterally) Agency Invested profile. Implications are discussed.
Generation of combined hepatocellular‐cholangiocarcinoma through transdifferentiation and dedifferentiation in p53‐knockout mice
Authors: Liu Yang , Xin Bing , Yamamoto Masahiro , Goto Masanori , Ooshio Takako , Kamikokura Yuki , Tanaka Hiroki , Meng Lingtong , Okada Yoko , Mizukami Yusuke , Nishikawa Yuji
Published: June 2021

The two principal histological types of primary liver cancers, hepatocellular carcinoma (HCC) and cholangiocarcinoma, can coexist within a tumor, comprising combined hepatocellular‐cholangiocarcinoma (cHCC‐CCA). Although the possible involvement of liver stem/progenitor cells has been proposed for the pathogenesis of cHCC‐CCA, the cells might originate from transformed hepatocytes that undergo ductular transdifferentiation or dedifferentiation. We previously demonstrated that concomitant introduction of mutant HRASV12 (HRAS) and Myc into mouse hepatocytes induced dedifferentiated tumors that expressed fetal/neonatal liver genes and proteins. Here, we examine whether the phenotype of HRAS‐ or HRAS/Myc‐induced tumors might be affected by the disruption of the Trp53 gene, which has been shown to induce biliary differentiation in mouse liver tumors. Hepatocyte‐derived liver tumors were induced in heterozygous and homozygous p53‐knockout (KO) mice by hydrodynamic tail vein injection of HRAS‐ or Myc‐containing transposon cassette plasmids, which were modified by deleting loxP sites, with a transposase‐expressing plasmid. The HRAS‐induced and HRAS/Myc‐induced tumors in the wild‐type mice demonstrated histological features of HCC, whereas the phenotype of the tumors generated in the p53‐KO mice was consistent with cHCC‐CCA. The expression of fetal/neonatal liver proteins, including delta‐like 1, was detected in the HRAS/Myc‐induced but not in the HRAS‐induced cHCC‐CCA tissues. The dedifferentiation in the HRAS/Myc‐induced tumors was more marked in the homozygous p53‐KO mice than in the heterozygous p53‐KO mice and was associated with activation of Myc and YAP and suppression of ERK phosphorylation. Our results suggest that the loss of p53 promotes ductular differentiation of hepatocyte‐derived tumor cells through either transdifferentiation or Myc‐mediated dedifferentiation.