bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damage and constitutes an antiviral target
Authors: Xia Bingqing , Shen Xurui , He Yang , Pan Xiaoyan , Wang Yi , Yang Feipu , Fang Sui , Wu Yan , Zuo Xiaoli , Xie Zhuqing , Jiang Xiangrui , Chi Hao , Meng Qian , Zhou Hu , Zhou Yubo , Cheng Xi , Chen Tong , Xin Xiaoming , Jiang Hualiang , Xiao Gengfu , Zhao Qiang , Zhang Lei-Ke , Shen Jingshan , Li Jia , Gao Zhaobing
Published: June 2020

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of the virus’ excessively damaging abilities remains unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is sufficient to cause acute respiratory distress syndrome (ARDS)-like damagein vitroandin vivo. Overexpression of 2-E protein induced rapid pyroptosis-like cell death in various susceptible cells and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damage in lung and spleen. Overexpressed 2-E protein formed cation channels in host cell membranes, eventually leading to membrane rupture. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent protective effects against the 2-E-induced damage bothin vitroandin vivo. Importantly, their channel inhibition, cell protection and antiviral activities were positively correlated with each other, supporting 2-E is a promising drug target against SARS-CoV-2.
Development and validation of a six-RNA binding proteins prognostic signature and candidate drugs for prostate cancer
Authors: Gao Lei , Meng Jialin , Zhang Yong , Gu Junfei , Han Zhenwei , Gao Shenglin , Wang Xiaolu
Published: June 2020

The dysregulation of RNA binding proteins (RBPs) play critical roles in the progression of several cancers. However, the overall functions of RBPs in prostate cancer (PCa) remain poorly understood. Therefore, we first identified 144 differentially expressed RBPs in tumors compared to normal tissues based on the TCGA dataset. Next, six RBP genes (MSI1, MBNL2, LENG9, REXO2, RNASE1, PABPC1L) were screened out as prognosis hub genes by univariate, LASSO and multivariate Cox regression and used to establish the prognostic signature. Further analysis indicated that high risk group was significantly associated with poor RFS, which was validated in the MSKCC cohort. Besides, patients in high risk group was closely associated with dysregulation of DNA damage repair pathway, copy number alteration, tumor burden mutation and low-respond to cisplatin (P < 0.001), bicalutamide (P < 0.001). Finally, three drugs (ribavirin, carmustine, carbenoxolone) were predicted using Connectivity Map. In summary, we identified a six-RBP gene signature and three candidate drugs against PCa, which may promote the individualized treatment and further improve the life quality of PCa patients.
Osmia lignaria(Hymenoptera: Megachilidae) produce larger and heavier blueberries than honey bees (Hymenoptera: Apidae)
Authors: Fortuin Christine Cairns , Gandhi Kamal JK
Published: June 2020

Fruit set, berry size, and berry weight were assessed for pollination by the solitary beeOsmia lignaria(Say) in caged rabbiteye blueberries (Vaccinium asheiReade, Ericales : Ericaceae), and compared to that of uncaged rabbiteye blueberries which were pollinated largely by honey bees (Apis melliferaL).O. linariaproduced berries that were 1.6mm larger in diameter and 0.45g heavier than uncaged blueberries. Fruit set was 40% higher in uncaged blueberries. This suggests thatOsmiabees can produce larger and heavier berry fruit, butO. lignariamay be less efficient at blueberry pollination as compared toA. melliferaunder field cage conditions.
Integrating single-cell RNA-seq and imaging with SCOPE-seq2
Authors: Liu Zhouzerui , Yuan Jinzhou , Lasorella Anna , Iavarone Antonio , Bruce Jeffrey N. , Canoll Peter , Sims Peter A.
Published: June 2020

Live cell imaging allows direct observation and monitoring of phenotypes that are difficult to infer from transcriptomics. However, existing methods for linking microscopy and single-cell RNA-seq (scRNA-seq) have limited scalability. Here, we describe an upgraded version of Single Cell Optical Phenotyping and Expression (SCOPE-seq2) for combining single-cell imaging and expression profiling, with substantial improvements in throughput, molecular capture efficiency, linking accuracy, and compatibility with standard microscopy instrumentation. We introduce improved optically decodable mRNA capture beads and implement a more scalable and simplified optical decoding process. We demonstrate the utility of SCOPE-seq2 for fluorescence, morphological, and expression profiling of individual primary cells from a human glioblastoma (GBM) surgical sample, revealing relationships between simple imaging features and cellular identity, particularly among malignantly transformed tumor cells.
Linking the dynamics of chromatin occupancy and transcription with predictive models
Authors: Tran Trung Q. , MacAlpine Heather K. , Tripuraneni Vinay , Mitra Sneha , MacAlpine David M. , Hartemink Alexander J.
Published: June 2020

Though the sequence of the genome within each eukaryotic cell is essentially fixed, it exists within a complex and changing chromatin state. This state is determined, in part, by the dynamic binding of proteins to the DNA. These proteins—including histones, transcription factors (TFs), and polymerases—interact with one another, the genome, and other molecules to allow the chromatin to adopt one of exceedingly many possible configurations. Understanding how changing chromatin configurations associate with transcription remains a fundamental research problem. We sought to characterize at high spatiotemporal resolution the dynamic interplay between transcription and chromatin in response to cadmium stress. While gene regulatory responses to environmental stress in yeast have been studied, how the chromatin state changes and how those changes connect to gene regulation remain unexplored. By combining MNase-seq and RNA-seq data, we found chromatin signatures of transcriptional activation and repression involving both nucleosomal and TF-sized DNA-binding factors. Using these signatures, we identified associations between chromatin dynamics and transcriptional regulation, not only for known cadmium response genes, but across the entire genome, including antisense transcripts. Those associations allowed us to develop generalizable models that can predict dynamic transcriptional responses on the basis of dynamic chromatin signatures.
Size-dependent protein segregation creates a spatial switch for Notch signaling and function
Authors: Kwak Minsuk , Southard Kaden M. , Kim Woon Ryoung , Kim Nam Hyeong , Gopalappa Ramu , An Minji , Lee Hyun Jung , Kang Min K. , Choi Seo Hyun , Farlow Justin , Georgakopoulos Anastasios , Robakis Nikolaos K. , Kutys Matthew L. , Seo Daeha , Kim Hyeong Bum , Kim Yong Ho , Cheon Jinwoo , Gartner Zev J. , Jun Young-wook
Published: June 2020

Aberrant cleavage of Notch by γ-secretase is implicated in numerous diseases, but how cleavage is regulated in space and time is unclear. Here, we report that cadherin-based adherens junctions (cadAJs) are sites of high cell-surface γ-secretase activity, as well as sites of constrained physical space that excludes γ-secretase substrates having large extracellular domains (ECDs) like Notch. ECD shedding initiates drastic spatial relocalization of Notch to cadAJs, allowing enzyme-substrate interactions and downstream signaling. Spatial mutations by adjusting the ECD size or the physical constraint alter signaling. Dysregulation of this spatial switch promotes precocious differentiation of ventricular zone neural progenitor cells in vivo. We show the generality of this spatial switch for amyloid precursor protein proteolysis. Thus, cadAJs create spatially distinct biochemical compartments regulating cleavage events involving γ-secretase and preventing aberrant activation of receptors.

One Sentence Summary

Notch cleavage by γ-secretase is regulated through dynamic spatial control of receptors, adhesion molecules, and activating proteases
Whole-brain dynamics in aging: disruptions in functional connectivity and the role of the rich club
Authors: Escrichs Anira , Biarnes Carles , Garre-Olmo Josep , Fernández-Real José Manuel , Ramos Rafel , Pamplona Reinald , Brugada Ramon , Serena Joaquin , Ramió-Torrentà Lluís , Coll-De-Tuero Gabriel , Gallart Luís , Barretina Jordi , Vilanova Joan C. , Mayneris-Perxachs Jordi , Essig Marco , Figley Chase R. , Pedraza Salvador , Puig Josep , Deco Gustavo
Published: June 2020

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state fMRI studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent (BOLD) signals to analyze resting-state fMRI data from 620 subjects divided into two groups (‘middle-age group’ (n=310); age range, 50-65 years vs. ‘older group’ (n=310); age range, 66-91 years). Applying the Intrinsic-Ignition Framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.
The primary motor cortex prospectively computes the spinal reflex
Authors: Umeda Tatsuya , Isa Tadashi , Nishimura Yukio
Published: June 2020

The spinal reflex transforms sensory signals to generate muscle activity. However, it is unknown how the motor cortex (MCx) takes the spinal reflex into account when performing voluntary limb movements. We simultaneously recorded the activity of the MCx, afferent neurons, and forelimb muscles in behaving monkeys. We decomposed muscle activity into subcomponents explained by the MCx or afferent activity using linear models. Long preceding activity in the MCx, which is responsible for subsequent afferent activity, had the same spatiotemporal contribution to muscle activity as afferent activity, indicating that the MCx drives muscle activity not only by direct descending activation but also by trans-afferent descending activation. Therefore, the MCx implements internal models that prospectively estimate muscle activation via the spinal reflex for precise movement control.
Anin vitroassessment of anti-SARS-CoV-2 activity of oral preparations of iodine complexes (RENESSANS)
Authors: Altaf Imran , Nadeem Muhammad Faisal , Hussain Nadir , Nawaz Muhammad , Raza Sohail , Ali Muhammad Asad , Hasan Sohail , Matti Nazish , Ashraf Muhammad , Ulla Ihsan , Fazal Sehar , Rafique Saira , Adnan Muhammad , Sardar Nageen , Khan Tahir , Moavia Muhammad , Ashraf Sohaib , Tahir Zarfishan , Mukhtar Nadia , Yaqub Tahir
Published: June 2020

Since the emergence of CoVID-19 pandemic in China in late 2019, scientists are striving hard to explore non-toxic, viable anti-SARS-CoV-2 compounds or medicines. We determinedIn Vitroanti-SARS-CoV-2 activity of oral formulations (syrup and capsule) of an Iodine-complex (Renessans). A monolayer of vero cells were exposed to SARS-CoV-2 in the presence and absence of different concentrations (equivalent to 50, 05 and 0.5 μg/ml of I2) of Renessans. Anti-SARS-CoV-2 activity of each of the formulation was assessed in the form of cell survival, SARS-CoV-2-specific cytopathic effect (CPE) and genome quantization. With varying concentrations of syrup and capsule, a varying rate of inhibition of CPE, cells survival and virus replication was observed. Compared to 0.5 μg/ml concentration of Renessans syrup, 5 and 50 μg/ml showed comparable results where there was a 100% cell survival, no CPEs and a negligible viral replication (ΔCT= 0.11 and 0.13, respectively). This study indicates that Renessans, containing iodine, may have potential activity against SARS-CoV-2 which needs to be further investigated in human clinical trials.
Predicting clinical drug response from model systems by non-linear subspace-based transfer learning
Authors: Mourragui Soufiane , Loog Marco , Vis Daniel J. , Moore Kat , Manjon Anna G. , van de Wiel Mark A. , Reinders Marcel J.T. , Wessels Lodewyk F.A.
Published: June 2020

Pre-clinical models have been the workhorse of cancer research for decades. While powerful, these models do not fully recapitulate the complexity of human tumors. Consequently, translating biomarkers of drug response from pre-clinical models to human tumors has been particularly challenging. To explicitly take these differences into account and enable an efficient exploitation of the vast pre-clinical drug response resources, we developed TRANSACT, a novel computational framework for clinical drug response prediction. First, TRANSACT employs non-linear manifold learning to capture biological processes active in pre-clinical models and human tumors. Then, TRANSACT builds predictors on cell line response only and transfers these to Patient-Derived Xenografts (PDXs) and human tumors. TRANSACT outperforms four competing approaches, including Deep Learning approaches, for a set of 15 drugs on PDXs, TCGA cohorts and 226 metastatic tumors from the Hartwig Medical Foundation data. For only four drugs Deep Learning outperforms TRANSACT. We further derived an algorithmic approach to interpret TRANSACT and used it to validate the approach by identifying known biomarkers to targeted therapies and we propose novel putative biomarkers of resistance to Paclitaxel and Gemcitabine.
Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states
Authors: Girbig Mathias , Misiaszek Agata D. , Vorländer Matthias K. , Lafita Aleix , Grötsch Helga , Baudin Florence , Bateman Alex , Müller Christoph W.
Published: June 2020

RNA polymerase III (Pol III) synthesises tRNAs and other short, essential RNAs. Human Pol III misregulation is linked to tumour transformation, neurodegenerative and developmental disorders, and increased sensitivity to viral infections. Pol III inhibition increases longevity in different animals but also promotes intracellular bacterial growth owing to its role in the immune system. This highlights the importance to better understand human Pol III transcription on a molecular level. Here, we present cryo-EM structures at 2.8 to 3.3 Å resolution of transcribing and unbound human Pol III purified from human suspension cells that were gene-edited by CRISPR-Cas9. We observe insertion of the TFIIS-like subunit RPC10 into the polymerase funnel, providing insights into how RPC10 triggers transcription termination. Our structures also resolve elements absent from S. cerevisiae Pol III such as the winged-helix domains of RPC5 and an iron-sulphur cluster in RPC6, which tethers the heterotrimer subcomplex to the Pol III core. The cancer-associated RPC7α isoform binds the polymerase clamp, potentially interfering with Pol III inhibition by the tumour suppressor MAF1, which may explain why overexpressed RPC7α enhances tumour transformation. Finally, the human Pol III structure allows mapping of disease-related mutations and might contribute to developing inhibitors that selectively target Pol III for therapeutic interventions.
microbialPhenotypes: An R package that analyzes high-throughput microbial phenotype data
Authors: Wu Peter I-Fan , Hu James C. , Siegele Deborah A.
Published: June 2020

Various microbial high-throughput phenotyping techniques have been vastly conducted to infer functions of genes, generating large numbers of valuable datasets whose potential in providing insights to characterize genes hasn’t been fully exploited. Therefore, computational tools that allow unbiased, systematic analysis of these data also have become vital. Here we describe a package that evaluates high-throughput microbial phenotype data by one or several sets of associated functional annotations are provided. In addition, some helper functions are provided to help clean high-throughput microbial phenotype data.
Real-Time Measurement of Stimulated Dopamine Release in Compartments of the AdultDrosophila melanogasterMushroom Body
Authors: Shin Mimi , Copeland Jeffrey M. , Venton B. Jill
Published: June 2020

Drosophila melanogaster, the fruit fly, is an exquisite model organism to understand neurotransmission. Dopaminergic signaling in theDrosophilamushroom body (MB) is involved in olfactory learning and memory, with different compartments controlling aversive learning (corner) vs appetitive learning (medial tip). Here, the goal was to develop techniques to measure endogenous dopamine in compartments of the MB for the first time. We compared three stimulation methods: acetylcholine (natural stimulus), P2X2(chemogenetics), and CsChrimson (optogenetics). Evoked dopamine release was measured with fast-scan cyclic voltammetry in isolated adultDrosophilabrains. Acetylcholine stimulated the largest dopamine release (0.40 μM), followed by P2X2(0.14 μM), and CsChrimson (0.07 μM). With the larger acetylcholine and P2X2stimulations, there were no regional or sex differences in dopamine release. However, with CsChrimson, dopamine release was significantly higher in the corner than the medial tip, and females had more dopamine than males. Michaelis-Menten modeling of the single-light pulse revealed no significant regional differences in Km, but the corner had a significantly lower Vmax(0.12 μM/s vs. 0.19 μM/s) and higher dopamine release (0.05 μM vs. 0.03 μM). Optogenetic experiments are challenging because CsChrimson is also sensitive to blue light used to activate green fluorescent protein, and thus, light exposure during brain dissection must be minimized. These experiments expand the toolkit for measuring endogenous dopamine release inDrosophila, introducing chemogenetic and optogenetic experiments for the first time. With a variety of stimulations, different experiments will help improve our understanding of neurochemical signaling inDrosophila.
Baclofen decreases compulsive alcohol drinking in rats characterised by reduced levels of GAT-3 in the central amygdala
Authors: Marti-Prats Lucia , Belin-Rauscent Aude , Fouyssac Maxime , Puaud Mickaёl , Cocker Paul J. , Everitt Barry J. , Belin David
Published: June 2020

While most individuals with access to alcohol drink it recreationally, about 5 % lose control over their intake and progressively develop an alcohol use disorder (AUD), characterised by compulsive alcohol drinking accompanied by decreased interest in alternative sources of reinforcement. The neural and molecular mechanisms underlying the vulnerability to switch from controlled to compulsive alcohol intake have not been fully characterized, so limiting the development of new treatments for AUD. It has recently been shown that rats having reduced levels of expression of the gamma-aminobutyric acid (GABA) transporter, GAT-3, in the amygdala tend to persist in seeking and drinking alcohol even when adulterated with quinine, suggesting that pharmacological interventions aimed at restoring GABA homeostasis in these individuals may provide a targeted treatment to limit compulsive alcohol drinking. Here, we tested the hypothesis that the GABABreceptor agonist baclofen, which decreases GABA release, specifically decreases compulsive alcohol drinking in vulnerable individuals. In a large cohort of Sprague-Dawley rats allowed to drink alcohol under an intermittent two-bottle choice procedure, a cluster of individuals was identified that persisted in drinking alcohol despite adulteration or the availability of an alternative ingestive reinforcer, saccharin. In these rats, that were characterised by decreased GAT-3 mRNA levels in the central amygdala, acute baclofen administration (1.5 mg/kg, intraperitoneal) resulted in a decrease in compulsive drinking. These results indicate that low GAT-3 mRNA levels in the central amygdala represent an endophenotype of AUD and that the associated compulsive alcohol drinking characteristic is sensitive to baclofen.
Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase
Authors: Chen Zhuoyao , Zhang Jinwei , Heilig Raphael , Sorrell Fiona J. , D’Angiolella Vincenzo , Fischer Roman , Alessi Dario R. , Bullock Alex N.
Published: June 2020

The BTB-Kelch protein KLHL3 is a Cullin3-dependent E3 ligase that mediates the ubiquitin-dependent degradation of kinases WNK1-4 to control blood pressure and cell volume. A crystal structure of KLHL3 has defined its binding to an acidic degron motif containing a PXXP sequence that is strictly conserved in WNK1, WNK2 and WNK4. Mutations in the second proline abrograte the interaction causing the hypertension syndrome pseudohypoaldosteronism type II. WNK3 shows a diverged degron motif containing 4 amino acid substitutions that remove the PXXP motif raising questions as to the mechanism of its binding. To understand this atypical interaction, we determined the crystal structure of the KLHL3 Kelch domain in complex with a WNK3 peptide. The electron density enabled the complete 11-mer WNK-family degron motif to be traced for the first time revealing several conserved features not captured in previous work, including additional salt bridge and hydrogen bond interactions. Overall, the WNK3 peptide adopted a conserved binding pose except for a subtle shift to accommodate bulkier amino acid substitutions at the binding interface. At the centre, the second proline was substituted by WNK3 Thr541, providing a unique phosphorylatable residue among the WNK-family degrons. Fluorescence polarisation and structural modelling experiments revealed that its phosphorylation would abrogate the KLHL3 interaction similarly to hypertension-causing mutations. Together, these data reveal how the KLHL3 Kelch domain can accommodate the binding of multiple WNK isoforms and highlight a potential regulatory mechanism for the recruitment of WNK3.
Gap junction internalization and processing in vivo: a 3D immuno-electron microscopy study
Authors: Norris Rachael P. , Terasaki Mark
Published: June 2020

Gap junctions have well-established roles in cell-cell communication by way of forming permeable intercellular channels. Less is understood about their internalization, which forms double membrane vesicles containing cytosol and membranes from another cell, called connexosomes or annular gap junctions. Here, we systematically studied the fate of connexosomes in intact ovarian follicles. High pressure frozen, serial sectioned tissue was immunogold labeled for Connexin 43. Within a volume of electron micrographs, every labeled structure was categorized and counted. Surface area measurements indicate that large connexosomes undergo fission. Subsequent modifications are separation of inner and outer membranes, loss of Cx43 from the outer membrane, and outward budding of the modified membranes. We also documented several clear examples of organelle transfer from one cell to another by gap junction internalization. We discuss how connexosome formation and processing may be a novel means for gap junctions to mediate cell-cell communication.
Overexpression ofblaOXA-58Gene Driven by ISAba3is Associated with Imipenem Resistance in a ClinicalAcinetobacter baumanniiIsolate from Vietnam
Authors: Nguyen Anh T. , Pham Son C. , Ly Anh K. , Nguyen Chau V.V. , Vu Thanh T. , Ha Tuan M.
Published: June 2020

The aim of this study was to investigate genetic structures and expression ofblaOXA-58 gene in fiveAcinetobacter baumanniiclinical isolates recovered from two hospitals in southern Vietnam during 2012-2014.A. baumanniiisolates were identified by automated microbiology systems and confirmed by PCR. All isolates were characterized as multidrug resistant by antimicrobials testing using the disk diffusion method. Four imipenem susceptible and one non-susceptible isolates (MIC > 32μg.ml−1) were identified by E-test. PCR amplification ofblaOXA-58gene upstream and downstream sequences revealed the presence of ISAba3at both locations in one multidrug resistant isolate. Semi quantitation ofblaOXA-51andblaOXA-58gene expression was performed by the 2−ΔΔCtmethod. TheblaOXA-51gene expression of five isolates showed little difference but the isolate bearing ISAba3-blaOXA-58-ISAba3exhibited significant higherblaOXA-58mRNA level. Higher β-lactamases activity in periplasmic than cytoplasmic fraction was found in most isolates. The isolate overexpressingblaOXA-58 gene possessed very high periplasmic enzyme activity. In conclusion, theA. baumanniiisolate bearing ISAba3-blaOXA-58gene exhibited high resistance to imipenem, corresponding to an overexpression ofblaOXA-58gene and very high periplasmic β-lactamases activity.
Changes to the growth and discount rates and asset impairment
Authors: Georges Maxeem
Published: June 2020

Purpose

With timeliness and measurement of asset impairments as well as management opportunistic behaviour being topical, since the issuance of Australian Accounting Standards Board (AASB) 136, this study aims to examine whether assumptions about growth and discount rates made about asset recoverable amounts determine asset impairments.

Design/methodology/approach

This study uses a sample of 450 firm-year observations representing 133 Australian listed firms from 2015 to 2018. An estimation model is used where asset impairments is the dependent variable, growth and discount rates are the variables of interest and several impairment indicators are included as controls.

Findings

The results show that the decrease in growth rate but not the increase in discount rate affects the recognition of large asset impairments, where firms decrease the growth rate in the year of recognition. A change in discount rate affects asset impairments only when it is higher than the industry average. Hence, the growth rate is the management’s tool of choice in the recognition of asset impairments.

Originality/value

This study provides additional insight into how AASB 136 is used in practice. This includes investigating the tools used by firms in the calculation of asset recoverable amount and whether firms provide important information, as a part of disclosure. The results are of interest to investors and policymakers because they highlight the need for more restrictions around growth rate assumptions and less variation in disclosure.
A model of traditional functional food consumption behaviour
Authors: Sumaedi Sik , Sumardjo
Published: June 2020

Purpose

This study aims to analyse the influence of descriptive norm, perceived behavioural control, perceived threat of non-communicable disease (NCD), healthy food extension education frequency, the frequency of healthy food community group meetings, healthy food-related newspapers/magazines usage frequency, healthy food-related websites usage frequency and healthy food-related social media usage frequency towards traditional functional food consumption behaviour, especially tempeh, in Indonesia.

Design/methodology/approach

This study collected data from 99 respondents who consumed traditional functional food. The data were analysed using multiple regression.

Findings

Traditional functional food consumption behaviour is significantly influenced by descriptive norm, perceived behavioural control and the frequency of healthy food community group meetings. The traditional functional food consumption behaviour is not affected by the perceived threat of NCD, healthy food extension education frequency, healthy food-related newspapers/magazines usage frequency, healthy food-related websites usage frequency and healthy food-related social media usage frequency.

Research limitations/implications

This research investigated only one functional food type and employed a purposive sampling technique. Future research should be conducted in other contexts to examine the stability of the research findings.

Practical implications

To improve traditional functional food consumption, it is essential to ensure that people can easily consume traditional functional food. It is also essential to develop an extension education strategy that involves the community's influential person/leader and healthy food community group meetings.

Originality/value

This paper is the first that investigates traditional functional foods consumption behaviour.
The impact of perceived stress on US millennials' external and emotional eating behavior
Authors: Okumus Bendegul , Ozturk Ahmet Bulent
Published: June 2020

Purpose

The purpose of this paper is to identify the relationship between Millennials' perceived stress and their external and emotional eating behaviors. Furthermore, the moderating effect of nutritional knowledge on the relationship between perceived stress and emotional eating and perceived stress and external eating of US Millennials was tested.

Design/methodology/approach

Data was collected from 649 Millennials between the ages of 18 and 35 in the United States, and structural equation modeling (SEM) was performed to test the study hypotheses.

Findings

This study extends the literature and provides further insights into the relationship between US Millennials' eating behavior and stress factors. Perceived stress positively influenced Millennials' emotional and external eating behavior, and nutritional knowledge significantly moderated the relationships between perceived stress and emotional eating and perceived stress and external eating.

Research limitations/implications

First, data was collected from Millennials living in the United States. Second, not all of the predictors, save one (perceived stress), were selected and hypothesized as predictors of Millennials' eating behavior. The paper provides the essential psychological elements of US Millennials' eating behavior.

Originality/value

If unbalanced eating and obesity are the result of negative psychological factors, the recommended diet models or physical exercise by themselves may be less effective at combating obesity and related health issues. This is because stress was found to be a highly significant reason for unbalanced eating, new and more practical stress coping strategies are needed to moderate unbalanced eating behavior.
Empirical approach to the sequential relationships between generation, relational capital and performance in family wineries in Spain
Authors: Fernandez-Olmos Marta , Diaz-Vial Isabel , Malorgio Giulio
Published: June 2020

Purpose

This study aims to focus on relational social capital in family wineries. Relational social capital is influenced by the family nature of the business and is at the same time a key antecedent of winery performance. The aim is to analyse these relationships in the qualified denomination of origin (DOC) Rioja wine industry (Spain).

Design/methodology/approach

Using a final sample of 110 family wineries, a Baron and Kenny approach was performed to investigate the causal and mediating relationships between the generation in control, relational social capital and family winery performance.

Findings

Using a final sample of 110 family wineries, the study demonstrates that later generations show a higher level of relational social capital, that the positive relationship between relational social capital and performance is maintained in a family firm sample and that the generation in control sequentially influence on performance through its influence on relational social capital.

Research limitations/implications

The main limitations are that empirical data were obtained only from DOC Rioja wine family businesses and a cross-sectional study was conducted.

Social implications

This study provides policymakers and family managers responsible for succession with a better understanding of the effects of transferring the business to the next generations in terms of relational social capital and performance.

Originality/value

To the best of the knowledge, this is the first study to examine the sequential relationships between generation, relational social capital and performance in DOC Rioja family wineries. The context of the DOC Rioja wine industry is particularly noteworthy for two reasons. First, in this industry, family-controlled firms predominate. Second, the DOC Rioja wine industry is focussed on the small-to-medium context, which has conventionally provided a very good area for the development of social capital theory.
The performance effects of management control instruments in different stages of new product development
Authors: Munck Jan Christoph , Tkotz Alexander , Heidenreich Sven , Wald Andreas
Published: June 2020

Purpose

The study builds on existing research in management control (MC) and innovation management. The purpose of this study is to identify patterns in the application of MC instruments which contribute to successful innovation. The application of MC instruments can reduce potential risks and make the new product development (NPD) process more transparent and efficient.

Design/methodology/approach

The authors use dyadic data to determine the effect of 58 MC instruments on NPD process stage-specific performance and subsequent innovation and firm success. To provide empirical evidence of each MC instrument’s effectiveness, three importance-performance matrix analyses were conducted that assess the impact of each MC instrument.

Findings

The authors identify patterns in the application of MC instruments which contribute to successful innovation activities and the authors determine the impact of MC instruments on NPD performance, innovation performance and firm performance in different stages of the NPD process.

Practical implications

The authors provide knowledge that can be used by managers to review their actual application of MC in the NPD process and to select their instrument set.

Originality/value

The authors contribute to the MC literature by examining data from a cross-industry study on the effects of MC instruments during the NPD process. The authors include a comprehensive set of MC instruments and show how their effect changes between the different stages of the NPD process.
An analysis of sustainability and channel coordination in a three-echelon supply chain
Authors: Huang Ruting , Yao Xin
Published: June 2020

Purpose

The purpose of this paper is to investigate the decision behaviors and channel coordination of a sustainable three-echelon supply chain with retailer-led game setting.

Design/methodology/approach

The authors develop game-theoretic models to examine the decision behaviors of channel members in a three-echelon supply chain consisting of one supplier, one distributor and one dominated retailer. The authors first formulate two models for centralized decision and decentralized decision. And then this paper proposes sub-supply chain coordination and a two-tariff contract to coordinate the full supply chain. Finally, some management insights are obtained with a case study.

Findings

The authors find that when faced with environmentally conscious consumers, the channel members can benefit from higher greening level; however, higher cost of green technologies would have negative impacts on manufacturer's effort. The analysis also shows that cooperation among players can improve the supply chain performance and help with environmental improvement.

Research limitations/implications

The findings provide important managerial insights for the three-echelon supply chain to achieve sustainable goals where the retailer bears the environmental responsibility. However, this paper also has some limitations with assuming risk-neutral channel members and symmetric information.

Originality/value

The findings of the study contribute to coordination and collaboration in sustainability of supply chains. The results provide important managerial insights for the three-echelon supply chain to achieve sustainable goals.
Insights from corporate social innovation: a research agenda
Authors: Tabares Sabrina
Published: June 2020

Purpose

The purpose of this study is to analyse the contributions, major discussions and trends in the literature driving the research agenda in corporate social innovation (CSI). This is done through a systematic review on CSI publications in an open time span. Salient themes and emerging research topics in this literature, as well as research questions and limitations, are identified, culminating in a discussion of what is next for CSI research.

Design/methodology/approach

A systematic review was undertaken from academic and grey literature. Results were analysed following a bibliometric and interpretative content analysis.

Findings

The study provides novel insights on CSI research by drawing attention to discussions around the consensus on a definition of CSI, its disciplinary origins and the denominations referring to this field. Although CSI struggles to gain independence as a research field, the evidence shows that CSI is a cross-disciplinary concept nourished by multiple disciplines.

Research limitations/implications

Analysis in this paper has implications for research by highlighting the state of scholarship on CSI. Given the use of multiple denominations of CSI, several studies using low diffused denominations could be discarded.

Originality/value

This research contributes to the body of knowledge in the field of CSI by bringing clarity to former discussions and by suggesting how the field can move forward to a more advanced and mature state in research.
Identification of consumption patterns: an empirical study in millennials
Authors: Escandon-Barbosa Diana , Hurtado-Ayala Andrea , Rialp-Criado Josep , Salas-Paramo Jairo A.
Published: June 2020

Purpose

Societal changes and technological development have brought about drastic lifestyle change in the past decades. This drastic change is evident when comparing the lifestyle and general characteristics of generations who have been born immersed in this technological context to those of other generations. The objective of this paper is to analyze brand image (BI) as determinant of brand attitude (AB), and the moderating effect of brand equity (BE), in the use of online information among millennial shoppers from Colombia. In general, the purpose of this paper is to contribute to existing literature related to the importance of generational membership in classifying individuals regarding brand perception (BI, AB and BE) and association with the use of shopping channels between different generations.

Design/methodology/approach

A hierarchical regression model is estimated with a sample of university students in Colombia who are considered potential coffee consumers, and who were classified as millennials based on their age.

Findings

The results support that BE effect has a greater impact on AB when consumers have a good BI. Millennials also use more online communication sources to create brand perceptions.

Originality/value

Nevertheless, few studies have concurrently analyzed the characteristics of brand building and types of sources of information (online vs offline). This paper attempts to analyze the behavior of millennial consumers and the use of information channels online vs offline to manage brand and analyze BI, AB and BE.
The dual orexin receptor antagonist daridorexant does not affect the pharmacokinetics of the BCRP substrate rosuvastatin
Authors: Zenklusen Isabelle , Muehlan Clemens , Ulc Ivan , Liška Jiří , Dingemanse Jasper
Published: June 2020

Daridorexant is a dual orexin receptor antagonist in clinical development for the treatment of insomnia. Breast‐cancer resistant protein (BCRP) is an efflux pump expressed in intestinal epithelium and hepatocytes, contributing to the absorption, distribution, and elimination of drugs and endogenous compounds. In vitro, daridorexant inhibits BCRP with an IC50 of 3.0 μmol/L. The BCRP substrate rosuvastatin is a cholesterol‐lowering drug, recommended for clinical drug–drug interaction (DDI) studies. In order to exclude an inhibitory effect of daridorexant on BCRP, this single‐centre, open‐label, two‐treatment Phase 1 study investigated the effect of daridorexant at steady state on the pharmacokinetics (PK) of single‐dose rosuvastatin in 20 healthy male subjects. In addition, safety and tolerability were assessed. A single oral dose of 10 mg rosuvastatin on Day 1 was followed by 96 hours observation. Thereafter, 25 mg daridorexant was administered once daily (o.d.) on Days 5–8 and in combination with 10 mg rosuvastatin on Day 8. On Days 9–12, subjects received 25 mg daridorexant alone. PK sampling was performed up to 120 hours after treatment administration. The results showed that concomitant administration of 25 mg daridorexant o.d. at steady state did not affect the exposure parameters of rosuvastatin in a relevant way, as indicated by the ratios of geometric means (GMRs) ([rosuvastatin + daridorexant]/[rosuvastatin alone]) of 0.93 for both Cmax and AUC0‐∞. Administration of a single dose of 10 mg rosuvastatin, multiple doses of 25 mg daridorexant alone or in combination were well tolerated. Taken together, daridorexant and BCRP substrates can be safely co‐administered.
English, Welsh and Irish Scholars in the New Universities of the Continent in the Later Middle Ages
Authors: EMLYN RHUN
Published: June 2020

When considering the experiences of medieval English, Welsh or Irish scholars in continental Europe historians have tended to focus on the older, more prestigious universities such as Paris or the numerous Italian centres of learning. There have been very few attempts to look systematically at the younger universities that were established in parts of northern Europe in the later Middle Ages, based on the assumption that very few students from England, Wales or Ireland studied at these institutions. By researching the matriculation registers of the universities of Cologne and Leuven, and using these universities as case studies, this article shows that a significant and increasing number of students were making their way to the new universities of the continent during the fifteenth century. These included a number of important figures in the political and ecclesiastical life of later medieval England. The article argues that these universities in fact played an important part in the academic life of England, and to a lesser degree Wales and Ireland. They enhanced the prospects of ambitious clerics, educated prominent figures in royal government, provided stepping stones to Italy, encouraged the pre‐existing political and economic links between England and the Low Countries and contributed towards the growth of humanism in England. By studying Cologne and Leuven we are given an insight into the process of migrating between universities, the effect of political and economic connections on university attendance and the role of universities in fostering more harmonious international relations.
From Territorial Cohesion to Regional Spatial Justice: The Well‐Being of Future Generations Act in Wales
Authors: Jones Rhys , Goodwin‐Hawkins Bryonny , Woods Michael
Published: June 2020

The European Union's flagship Cohesion Policy faces evidence of dubious economic effectiveness and growing political and philosophical critiques of the very ideals of furthering European integration. This article examines ambitions for territorial cohesion as they have been operationalized through regional development in Wales. We argue that a potential alternative to the failed realization of territorial cohesion lies in the principles of spatial justice. While territorial cohesion has typically emphasized the redistribution of funds to ‘lagging’ regions, spatial justice, as we define it, is premised upon enabling regions to assert their own capacity to act and pursue positive visions of regional futures, consider the implications of space and scale for the achievement of justice, and define well‐being, development and the ‘good life’ in ways that reflect regional priorities. We examine three ways in which recent political discourses and policy mechanisms in Wales resonate with these ideals. We focus on attempts to envision a progressive Welsh future, develop alternative spaces and scales of governance, and redefine and pluralize understandings of progress and well‐being. The article concludes by reflecting on the practical and conceptual implications of rescaling spatial justice to regional contexts.
The Application of Photogrammetry in the Autopsy Room: A Basic, Practical Workflow*
Authors: Gitto Lorenzo , Donato Laura , Di Luca Alessandro , Bryant Stephanie M. , Serinelli Serenella
Published: June 2020

Photogrammetry is a technique that uses two‐dimensional photographs taken from different angles and positions to determine three‐dimensional coordinates and distances. Becoming familiar with the photography technique for photogrammetry purposes is the first step to obtaining high‐quality results. Ten human cadavers were studied to develop this protocol. Appropriate equipment settings, measurements, and suitable ambient conditions were determined. Finally, the protocol was tested on one cadaver wherein a full postmortem examination was conducted, allowing accurate 3D modeling and measurements of the human body. This straightforward, step‐by‐step workflow will help users become familiar with this technique. A thorough description of the necessary steps is reported, including equipment, environment requirements, body placement, how to take photographs, and the minimum suggested number of photographs. Numerous graphics show the protocol's main steps to help users understand and reproduce the entire process. Photogrammetry allows the permanent recording and storage of photographic evidence of conditions that existed at the time of autopsy and accurate measurements of the body. The 3D model can have a powerful effect in court, where the findings can be accurately depicted without elicitation of strong emotion that may influence the judge or jurors. The primary disadvantage of photogrammetry for forensic pathology is its time‐consuming nature. However, the widespread use of the photogrammetry technique in postmortem rooms would allow in‐depth testing to detect and fix potential pitfalls, making this technique more reproducible and verifiable, increasing its admissibility in courts.
High‐efficiency transformation of archaea by direct PCR products with its application to directed evolution of a thermostable enzyme
Authors: Song Yunhong , Zhu Zhiguang , Zhou Wei , Zhang Yi‐Heng P. Job
Published: June 2020

Hyperthermophilic archaea with unique biochemical and physiological characteristics are important organisms for fundamental research of life science and have great potential for biotechnological applications. However, low transformation efficiency of foreign DNA molecules impedes developments in genetic modification tools and industrial applications. In this study, we applied prolonged overlap extension PCR (POE‐PCR) to generate multimeric DNA molecules and then transformed them into two hyperthermophilic archaea, Thermococcus kodakarensis KOD1 and Pyrococcus yayanosii A1. This study was the first example to demonstrate the enhanced transformation efficiencies of POE‐PCR products by a factor of approximately 100 for T. kodakarensis KOD1 and 8 for P. yayanosii A1, respectively, relative to circular shuttle plasmids. Furthermore, directed evolution of a modestly thermophilic enzyme, Methanothermococcus okinawensis 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGR), was conducted to obtain more stable ones due to high transformation efficiency of T. kodakarensis (i.e. ~3 × 104 CFU per μg DNA). T. kodakarensis harbouring the most thermostable MoHMGR mutant can grow in the presence of a thermostable antibiotic simvastatin at 85°C and even higher temperatures. This high transformation efficiency technique could not only help develop more hyperthermophilic enzyme mutants via directed evolution but also simplify genetical modification of archaea, which could be novel hosts for industrial biotechnology.