bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of amino acid residues involved in the interaction between peste-des-petits-ruminants virus haemagglutinin protein and cellular receptors
Authors: meng Xuelian , Zhu Xueliang , Alfred Niyokwishimira , Zhang Zhidong
Published: December 2019

Peste-des-petits-ruminants virus (PPRV) haemagglutinin (H) protein mediates binding to cellular receptors and then initiates virus entry. To identify the key residues of PPRV H (Hv) protein of the Nigeria 75/1 strain involved in binding to receptors, interaction of the Hv and mutated Hv (mHv) proteins with receptors (SLAM and Nectin 4) and their mutants (mSLAM1, mSLAM2, mSLAM3 and mNectin 4) was investigated using surface plasmon resonance imaging (SPRi) and coimmunoprecipitation (co-IP) assays. The results showed that the Hv protein failed to interact with mSLAM3, but interacted at a strong or medium intensity with SLAM, mSLAM2, Nectin 4 and mNectin 4, and at a low level with mSLAM1. The mHv protein was unable to interact with SLAM and its mutants, but bound to Nectin 4 and mNectin 4 with medium and weak intensity, respectively. Further analysis showed that the Hv protein could precipitate mSLAM1, mSLAM2 and mNectin 4, but not mSLAM3. The mHv protein failed to coprecipitate with SLAM and its mutants. The binding activities of mNectin 4 and Nectin 4 to mHv were less than 30.36 and 51.94 % of the wild-type levels, respectively. Based on the results obtained, amino acids at positions R389, L464, I498, R503, R533, Y541, Y543, F552 and Y553 of H protein and I61, H62, L64, K76, K78, E123, H130, I210, A211, S226 and R227 in SLAM were identified to be essential for the speciﬁcity of H–SLAM interaction, while the critical residues of H–Nectin 4 interaction require further study. These findings would improve our understanding of the invasive mechanisms of PPRV.
Diverse demographic histories in a guild of hymenopteran parasitoids
Authors: Walton William , Stone Graham N , Lohse Konrad
Published: December 2019

Signatures of changes in population size have been detected in genome-wide variation in many species. However, the causes of such changes and the extent to which they are shared across co-distributed species remain poorly understood. During Pleistocene glacial maxima, many temperate European species were confined to southern refugia. While vicariance and range expansion processes associated with glacial cycles have been widely studied, little is known about the demographic history of refugial populations, and the extent and causes of demographic variation among codistributed species. We used whole genome sequence data to reconstruct and compare demographic histories during the Quaternary for Iberian refuge populations in a single ecological guild (seven species of chalcid parasitoid wasps associated with oak cynipid galls). We find support for large changes in effective population size (Ne) through the Pleistocene that coincide with major climate change events. However, there is little evidence that the timing, direction and magnitude of demographic change are shared across species, suggesting that demographic histories are largely idiosyncratic. Our results are compatible with the idea that specialist parasitoids attacking a narrow range of hosts experience greater fluctuations inNethan generalists.
PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis
Authors: Danileviciute Egle , Zeng Ni , Capelle Christophe , Paczia Nicole , Gillespie Mark A. , Kurniawan Henry , Coowar Djalil , Vogt Weisenhorn Daniela Maria , Giro Gemma Gomez , Grusdat Melanie , Baron Alexandre , Guerin Coralie , Franchina Davide G. , Léonard Cathy , Domingues Olivia , Delhalle Sylvie , Wurst Wolfgang , Schwamborn Jens Christian , Krüger Rejko , Ranish Jeff , Brenner Dirk , Linster Carole L. , Balling Rudi , Ollert Markus , He Feng Q.
Published: December 2019

Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme into the tricarboxylic acid (TCA) cycle. Here we show that PARK7/DJ-1, a key familial Parkinson’s disease (PD) gene, is a pacemaker controlling PDH activity in CD4 regulatory T cells (Tregs). DJ-1 bound to PDH-E1 beta (PDHB), inhibiting the phosphorylation of PDH-E1 alpha (PDHA), thus promoting PDH activity and oxidative phosphorylation (OXPHOS).Dj-1depletion impaired Treg proliferation and cellularity maintenance in older mice, increasing the severity during the remission phase of experimental autoimmune encephalomyelitis (EAE). The compromised proliferation and differentiation of Tregs inDj-1knockout mice were caused via regulating PDH activity. These findings provide novel insight into the already complicated regulatory machinery of the PDH complex and demonstrate that the DJ-1-PDHB axis represents a potent target to maintain Treg homeostasis, which is dysregulated in many complex diseases.
SSnet: A Deep Learning Approach for Protein-Ligand Interaction Prediction
Authors: Verma Niraj , Qu Xingming , Trozzi Francesco , Elsaied Mohamed , Karki Nischal , Tao Yunwen , Zoltowski Brian , Larson Eric C. , Kraka Elfi
Published: December 2019

Computational prediction of Protein-Ligand Interaction (PLI) is an important step in the modern drug discovery pipeline as it mitigates the cost, time, and resources required to screen novel therapeutics. Deep Neural Networks (DNN) have recently shown excellent performance in PLI prediction. However, the performance is highly dependent on protein and ligand features utilized for the DNN model. Moreover, in current models, the deciphering of how protein features determine the underlying principles that govern PLI is not trivial. In this work, we developed a DNN framework named SSnet that utilizes secondary structure information of proteins extracted as the curvature and torsion of the protein backbone to predict PLI. We demonstrate the performance of SSnet by comparing against a variety of currently popular machine and non-machine learning models using various metrics. We visualize the intermediate layers of SSnet to show a potential latent space for proteins, in particular to extract structural elements in a protein that the model finds influential for ligand binding, which is one of the key features of SSnet. We observed in our study that SSnet learns information about locations in a protein where a ligand can bind including binding sites, allosteric sites and cryptic sites, regardless of the conformation used. We further observed that SSnet is not biased to any specific molecular interaction and extracts the protein fold information critical for PLI prediction. Our work forms an important gateway to the general exploration of secondary structure based deep learning, which is not just confined to protein-ligand interactions, and as such will have a large impact on protein research while being readily accessible forde novodrug designers as a standalone package.
Real-time monitoring of cotranscriptional riboswitch folding and switching
Authors: Hua Boyang , Jones Christopher P. , Mitra Jaba , Murray Peter J. , Rosenthal Rebecca , Ferré-D’Amaré Adrian R. , Ha Taekjip
Published: December 2019

Riboswitches function through cotranscriptional conformation switching governed by cognate ligand concentration, RNA folding and transcription elongation kinetics. To investigate how these parameters influence riboswitch folding, we developed a novel vectorial folding assay (VF) in which the superhelicase Rep-X sequentially liberates the RNA strand from a heteroduplex in a 5’-to-3’ direction, mimicking the nascent chain emergence during transcription. The RNA polymerase (RNAP)-free VF recapitulates the kinetically controlled cotranscriptional folding of a ZTP riboswitch, whose activation is favored by slower transcription, strategic pausing, or a weakened transcriptional terminator. New methods to observe positions and local rates of individual helicases show an average Rep-X unwinding rate similar to bacterial RNAP elongation (~60 nt/s). Real-time single-molecule monitoring captured folding riboswitches in multiple states, including an intermediate responsible for delayed terminator formation. These methods allow observation of individual folding RNAs as they occupy distinct folding channels within the landscape that controls gene expression and showed that riboswitch fate control is encoded in its sequence and is readily interpreted by a directionally moving protein even in the absence of an RNA polymerase.
Genotyping and functional regression trees reveals environmental preferences of toxic cyanobacteria (Microcystis aeruginosacomplex) along a wide spatial gradient
Authors: Martínez de la Escalera Gabriela , Segura Angel M. , Kruk Carla , Ghattas Badih , Piccini Claudia
Published: December 2019

Addressing ecological and evolutionary processes explaining biodiversity patterns is essential to identify the mechanisms driving community assembly. In the case of bacteria, the formation of new ecologically distinct populations or ecotypes is proposed as one of the main drivers of diversification. New ecotypes arise when mutation in key functional genes or acquisition of new metabolic pathways by horizontal gene transfer allow the population to exploit new resources, making possible their coexistence with parental population. Recently, we have reported the presence of toxic, microcystin-producing organisms from theMicrocystis aeruginosacomplex (MAC) through a wide environmental gradient (800 km) in South America, ranging from freshwater to estuarine-marine waters. In order to explain this finding, we hypothesize that the success of toxic organisms of MAC in such array of environmental conditions is due to the existence of ecotypes having different environmental preferences. So, we analysed the genetic diversity of microcystin-producing populations ofMicrocystis aeruginosacomplex (MAC) by qPCR and high resolution melting analysis (HRMA) of a functional gene (mcyJ, involved in microcystin synthesis) and explored its relationship with the environmental conditions through the gradient by functional classification and regression trees (fCART). Six groups ofmcyJgenotypes were distinguished and selected by different combinations of water temperature, conductivity and turbidity, determining the environmental preferences of each group. Since these groups were based on the basis of similar sequence and ecological characteristics they were defined as ecotypes of toxic MAC. Taking into account that the role of microcystins in MAC biology and ecology has not yet been elucidated, we propose that the toxin might have a role in MAC fitness that would be mainly controlled by the physical environment in a way such that the ecotypes that thrive in the riverine zone of the gradient would be more stable and less influenced by salinity fluctuations than those living at the marine limit of the estuary. These would periodically disappear or being eliminated by salinity increases, depending on the estuary dynamics. Thus, ecotypes generation would be an important mechanism allowing toxic MAC adapting to and succeed in a wide array of environmental conditions.
Niacin Stimulates Mammary Gland Development in Pubertal Mice through Activation of the AKT/mTOR and ERK1/2 Signaling Pathways
Authors: Cao Yu , Liu Juxiong , Ma Lijun , Zhang Qing , Wang Jiaxin , Guo Wenjin , Li Yanwei , Cheng Ji , Fu Shoupeng
Published: December 2019

Previous studies have shown the effects of vitamins on the development of the mammary gland. However, the role of niacin in this process has not been reported. Therefore, the aim of this study was to investigate the effects of niacin on mammary gland development in pubertal mice and to use a mouse mammary epithelial cell line to study the underlying mechanism. The results showed that niacin could activate the AKT/mTOR and ERK signaling pathways by the Gi protein-coupled receptor and increase phosphorylation of 4EBP1 to promote the synthesis of cell proliferation markers, leading to the dissociation of the Rb-E2F1 complex in mMECs. In addition, 0.5% niacin promoted mammary duct development, increased the expression of cyclin D1/D3 and PCNA, and activated Akt/mTOR and ERK1/2 in the mammary glands of pubertal mice. These results strongly suggest that niacin stimulates mammary gland development in pubertal mice through the Akt/mTOR and ERK1/2 signaling pathways and that the Gi protein-coupled receptor is essential for this function.
A dynamic normalization model of temporal attention
Authors: Denison Rachel N. , Carrasco Marisa , Heeger David J.
Published: December 2019

Vision is dynamic, handling a continuously changing stream of input, yet most models of visual attention are static. Here, we develop a dynamic normalization model of visual temporal attention and constrain it with new psychophysical human data. We manipulated temporal attention–the prioritization of visual information at specific points in time–to a sequence of two stimuli separated by a variable time interval. Voluntary temporal attention improved perceptual sensitivity only over a specific interval range. To explain these data, we modeled voluntary and involuntary attentional gain dynamics. Voluntary gain enhancement took the form of a limited resource over short time intervals, which recovered over time. Taken together, our theoretical and experimental results formalize and generalize the idea of limited attentional resources across space at a single moment to limited resources across time at a single location.
Distinct relations of microtubules and actin filaments with dendritic architecture
Authors: Nanda Sumit , Bhattacharjee Shatabdi , Cox Daniel N. , Ascoli Giorgio A.
Published: December 2019

Microtubules and F-actin have long been recognized as key regulators of dendritic morphology. Nevertheless, precisely ascertaining their distinct influences on dendritic trees have been hampered until now by the lack of direct, arbor-wide cytoskeletal quantification. We pair live confocal imaging of fluorescently labeled dendritic arborization (da) neurons in Drosophila larvae with complete multi-signal neural tracing to separately measure microtubules and F-actin. We demonstrate that dendritic arbor length is highly interrelated with local microtubule quantity, whereas local F-actin enrichment is associated with dendritic branching. Computational simulation of arbor structure solely constrained by experimentally observed subcellular distributions of these cytoskeletal components generated synthetic morphological and molecular patterns statistically equivalent to those of real da neurons, corroborating the efficacy of local microtubule and F-actin in describing dendritic architecture. The analysis and modeling outcomes hold true for the simplest (Class I), most complex (Class IV), and genetically altered (Formin3 overexpression) da neuron types.

SUPPORT: NIH R01 NS39600 and NS086082 and BICCN U01 MH114829.
Detection of genome-wide low-frequency mutations with Paired-End and Complementary Consensus Sequencing (PECC-Seq) revealed end-repair derived artifacts as residual errors
Authors: You Xinyue , Thiruppathi Suresh , Liu Weiying , Cao Yiyi , Naito Mikihiko , Furihata Chie , Honma Masamitsu , Luan Yang , Suzuki Takayoshi
Published: December 2019

To improve the accuracy and the cost-efficiency of next-generation sequencing in ultralow-frequency mutation detection, we developed the Paired-End and Complementary Consensus Sequencing (PECC-Seq), a PCR-free duplex consensus sequencing approach. PECC-Seq employed shear points as endogenous barcodes to identify consensus sequences from the overlap in the shortened, complementary DNA strands-derived paired-end reads for sequencing error correction. With the high accuracy of PECC-Seq, we identified the characteristic base substitution errors introduced by the end-repair process of mechanical fragmentation-based library preparations, which were prominent at the terminal 6 bp of the library fragments in the 5’-NpCpA-3’ or 5’-NpCpT-3’ trinucleotide context. As demonstrated at the human genome scale (TK6 cells), after removing these potential end-repair artifacts from the terminal 6 bp, PECC-Seq could reduce the sequencing error frequency to mid-10−7with a relatively low sequencing depth. For TA base pairs, the background error rate could be suppressed to mid-10−8. In mutagen-treated TK6, slight increases in mutagen treatment-related mutant frequencies could be detected, indicating the potential of PECC-Seq in detecting genome-wide ultra-rare mutations. In addition, our finding on the patterns of end-repair artifacts may provide new insights in further reducing technical errors not only for PECC-Seq, but also for other next-generation sequencing techniques.
The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification
Authors: Wells Carrow I. , Al-Ali Hassan , Andrews David M. , Asquith Christopher R. M. , Axtman Alison D. , Chung Mirra , Dikic Ivan , Ebner Daniel , Elkins Jonathan M. , Ettmayer Peter , Fischer Christian , Frederiksen Mathias , Gray Nathanael S. , Hatch Stephanie , Knapp Stefan , Lee Shudong , Lücking Ulrich , Michaelides Michael , Mills Caitlin E. , Müller Susanne , Owen Dafydd , Picado Alfredo , Ramadan Kristijan , Saikatendu Kumar S. , Schröder Martin , Stolz Alexandra , Tellechea Mariana , Treiber Daniel K. , Turunen Brandon J. , Vilar Santiago , Wang Jinhua , Zuercher William J. , Willson Timothy M. , Drewry David H.
Published: December 2019

We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
Multi-corneal barriers-on-a-chip to recapitulate eye blinking shear stress forces
Authors: Abdalkader Rodi , Kamei Ken-ichiro
Published: December 2019

Human corneal epithelium coexists tear fluids and shows its barrier functionality under the dynamic conditions of eye blinking. However, the current in vitro cell culture settings for corneal epithelial cells lack the dynamic flow conditions to recapitulate shear stress of eye blinking, hindering corneal function evaluation. We developed a microfluidic platform enabling the dynamic culture of the human corneal barrier with recapitulation of eye blinking. The device consisted of upper and lower channels separated by a porous membrane. Human corneal epithelial cells (HCE-T) were seeded on a porous membrane in an upper channel and cultured for ten days. The cells formed a barrier with high expression of zonula occludens 1 (ZO-1) tight junction protein on day seven, and the translocation of fluorescein sodium across the barrier in the microfluidic device was comparable to that in the transwell system. Then, bidirectional and unidirectional flows were applied in the upper and lower channels, respectively, and the cells in the upper channels were stimulated with 0.6 dyn s cm-2 of shear stress. While the fluid stimuli after 24 h did not affect cell adhesion, the flow stimuli facilitated the expression of cytokeratin 19 (CK-19) intermediate filaments in cells after 24 h, indicating strengthening of the barrier function. Furthermore, the morphological single-cell analysis revealed an increase in cell body area rather than nuclei. We envision that this multicorneal barriers-on-a-chip device will unlock new possibilities in ophthalmic drug development and will be useful for studying the mechanobiology of the ocular surface.
Discovery of dual inhibitors of KPC-3 and KPC-15 of Klebsiella pneumoniae – an in-silico molecular docking and dynamics study
Authors: Sharma Sony , Kumar-M Praveen , Singh Santa , Sohal Ajay , Yadav Rohitash , Gupta Nitin
Published: December 2019

Background

The development of carbapenem resistance against Klebsiella pneumoniae is a situation of grave concern and requires urgent attention. Among the KPC produced by K.pneumoniae, KPC-3, and KPC-15, play a significant role in the development of resistance to carbapenem.

Materials and methods

The binding sites of KPC-3 and KPC-15 were predicted by the COACH server. Drug-like ligands from ZINC were then screened by ligand-based drug screening (LBVS) by keeping Relebactam as a template. The top 50,000 selected ligands were then screened by structure-based virtual screening using idock. For keeping an account of the dual inhibitors’ stability in complex with KPC-3 and KPC-15, MDS were carried out for each complex.

Results

Based on consensus weighted ranks, the top 3 ligands with the dual inhibitory property are ZINC76060350 (consensus weighted rank - 1.5), ZINC05528590 (2), ZINC72290395 (3.5). All the top 3 dual inhibitors have a reasonable probability of passing through the blood-brain barrier. The RDKit and Morgan fingerprint scores between Relebactam and the top three ligands were 0.24, 0.22, 0.23, and 0.26, 0.19, 0.25, respectively (showing only 20% similarity). The MD simulation result revealed good binding stability of ligand ZINC05528590 with both KPC-3 and KPC-15, whereas ligand ZINC76060350 showed good binding stability to KPC-3.

Conclusion

The ligand ZINC05528590 could be taken forward to develop a new drug against a multi-resistant- Klebsiella pneumoniae infection. At the same time, ZINC76060350 can be considered to develop a new drug against KPC-15 resistant Klebsiella pneumoniae.
An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of a-synuclein
Authors: Kara Eleanna , Crimi Alessandro , Wiedmer Anne , Emmenegger Marc , Manzoni Claudia , Bandres-Ciga Sara , D’Sa Karishma , Reynolds Regina H , Botía Juan A , Losa Marco , Lysenko Veronika , Carta Manfredi , Heinzer Daniel , Avar Merve , Chincisan Andra , Blauwendraat Cornelis , Ruiz Sonia Garcia , Pease Daniel , Mottier Lorene , Carrella Alessandra , Schneider Dezirae , Magalhaes Andreia , Aemisegger Caroline , Theocharides Alexandre P A , Fan Zhanyun , Marks Jordan D , Hopp Sarah C , Lewis Patrick , Ryten Mina , Hardy John , Hyman Bradley T , Aguzzi Adriano
Published: December 2019

Neuropathological and experimental evidence suggests that the cell-to-cell transfer of a-synuclein has an important role in the pathogenesis of Parkinson’s disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook an siRNA, genome-wide high throughput screen to identify genes regulating the cell-to-cell transfer of a-synuclein. We transiently transfected HEK cells stably overexpressing a-synuclein with a construct encoding GFP-2a-aSynuclein-RFP. The cells expressing a-synuclein-RFP through transfection were double positive for GFP and RFP fluorescence, whereas the cells receiving it through transfer were positive only for RFP fluorescence. The amount of a-synuclein transfer was quantified by high content microscopy. A series of unbiased screens confirmed the involvement of 38 genes in the regulation of a-synuclein-RFP transfer. One of those hits wasITGA8, a candidate gene recently identified through a large PD genome wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) showed that the hits clustered in networks that included known PD Mendelian and GWAS risk genes more frequently than expected than random chance. Given the genetic overlap between a-synuclein transfer and PD, those findings provide supporting evidence for the importance of the cell-to-cell transfer of a-synuclein in the pathogenesis of PD, and expand our understanding of the mechanism of a-synuclein spread.
Using Phaser and ensembles to improve the performance of SIMBAD
Authors: Simpkin Adam J. , Simkovic Felix , Thomas Jens M. H. , Savko Martin , Lebedev Andrey , Uski Ville , Ballard Charles C. , Wojdyr Marcin , Shepard William , Rigden Daniel J. , Keegan Ronan M.
Published: December 2019

The conventional approach to search-model identification in molecular replacement (MR) is to screen a database of known structures using the target sequence. However, this strategy is not always effective, for example when the relationship between sequence and structural similarity fails or when the crystal contents are not those expected. An alternative approach is to identify suitable search models directly from the experimental data. SIMBAD is a sequence-independent MR pipeline that uses either a crystal lattice search or MR functions to directly locate suitable search models from databases. The previous version of SIMBAD used the fast AMoRe rotation-function search. Here, a new version of SIMBAD which makes use of Phaser and its likelihood scoring to improve the sensitivity of the pipeline is presented. It is shown that the additional compute time potentially required by the more sophisticated scoring is counterbalanced by the greater sensitivity, allowing more cases to trigger early-termination criteria, rather than running to completion. Using Phaser solved 17 out of 25 test cases in comparison to the ten solved with AMoRe, and it is shown that use of ensemble search models produces additional performance benefits.
Towards innovation, co-creation and customers’ satisfaction: a banking sector perspective
Authors: Malik Muhammad Imran , Ahsan Rizwan
Published: December 2019

Purpose

Co-creation fosters customer’s involvement for innovation in products/services and is used as a tool to develop competitive edge for better entrepreneurship. Based on limited evidence, the study aims to examine the factors contributing to the co-creation and the relationship of co-creation with customer satisfaction.

Design/methodology/approach

A sample of 384 customers from selected banks in Pakistan was selected. The study adopted quantitative, explanatory and cross-sectional research design. Structural equation modeling is used for analysis.

Findings

The results revealed a positive and significant relationship between co-creation with customer satisfaction. Further results revealed that access to information, risk assessment and transparency have a positive relationship with co-creation for innovation. The study is significant for customers and management of banks to understand the implications of co-creation to increase customer satisfaction.

Research limitations/implications

Few banks with a small number of customers were selected for the study.

Practical implications

Managers must consider customer’s access to information, risk assessment and transparency of information as necessary factors for co-creation that foster innovation and entrepreneurial opportunities because co-creation strengthens customer satisfaction.

Social implications

Adopting the co-creation process brings long-lasting harmony between customers and banks, and customers may consider the banks as being socially responsible by inviting the opinions of their customers.

Originality/value

Model is re-tested in the context of Pakistani banks with selected variables affecting co-creation for innovation. Moreover, the relationship of co-creation with customer satisfaction is examined.
Generational differences in risk perception and situational uses of wine information sources
Authors: Bauman Matthew J. , Velikova Natalia , Dodd Tim , Blankenship Trey
Published: December 2019

Purpose

The purpose of this study is to examine generational differences in consumer Web 2.0 information source adoption for wine purchasing decisions, particularly social media and internet-based sources.

Design/methodology/approach

An online survey resulted in 276 responses from wine consumers residing in Texas, USA. Information source usage was tested in two common purchasing situations: for casual and formal consumption. Chi-square analyses and ANOVA were used to examine differences among the generational cohorts in their use of information sources, levels of objective and subjective wine knowledge, wine involvement and risk perception for the two purchasing situations.

Findings

Younger consumers were found to be significantly more inclined to use Web 2.0 information sources, such as wine blogs, wine applications, their contacts’ recommendations on social media and wine experts on social media. Older consumers were more likely to use their own wine knowledge. Of greater interest is that in terms of their reliance on various wine information sources, Generation X behaves as the bridge between Generation Y and Baby Boomers. Generational differences regarding wine involvement, wine knowledge and risk perception also support this notion.

Practical implications

The results of this study reinforce the need for wineries to adopt or create strategic initiatives using Web 2.0 elements. This study also suggests that depending on the purchasing context, consumers use certain information sources more than others.

Originality/value

This research extends the understanding of the information acquisition process by expanding the types of information sources, and also yields valuable insights for consumers’ off-premise wine purchasing decisions.
Axial strength of modified fibrous foamed concrete-filled hollow section
Authors: Abd Rahman Norashidah , Khairuddin Siti Amirah Azra , Faudzi Mohd Faris , Mohd Asri Mohd Harith Imran , Jamaluddin Norwati , Mohd Jaini Zainorizuan
Published: December 2019

Purpose

Concrete-filled hollow section (CFHS) is widely used in steel construction. The combination of concrete and steel decreases buckling and deformation of steel. However, studies reveal that using normal concrete increases the dead weight of a structure. Therefore, a lightweight concrete, such as foamed concrete (FC), is proposed to reduce the weight of the structure. The purpose of this study is to determine the strength of modified fibrous foamed CFHS (FCFHS).

Design/methodology/approach

Steel and polypropylene fibres were used with rice husk ash, and short column fibrous FCFHSs were tested under compression load. Greased and non-greased methods were adopted to determine bond strength and confining effect between steel and concrete.

Findings

Results indicate that the use of fibre in FCFHSs improves the strength of CFHS from 9% to 11%. The non-greased method confirms that an interaction exists between steel and concrete with a confinement coefficient of more than 2.0.

Originality/value

It can be shown that the modified fibrous foamed concrete can increase the strength of the concrete and can be used as concrete filled in steel construction industry.
Elastic full waveform inversion with probabilistic petrophysical clustering
Authors: Aragao Odette , Sava Paul
Published: December 2019

Full waveform inversion aims to use all information provided by seismic data to deliver high‐resolution models of subsurface parameters. However, multiparameter full waveform inversion suffers from an inherent trade‐off between parameters and from ill‐posedness due to the highly non‐linear nature of full waveform inversion. Also, the models recovered using elastic full waveform inversion are subject to local minima if the initial models are far from the optimal solution. In addition, an objective function purely based on the misfit between recorded and modelled data may honour the seismic data, but disregard the geological context. Hence, the inverted models may be geologically inconsistent, and not represent feasible lithological units. We propose that all the aforementioned difficulties can be alleviated by explicitly incorporating petrophysical information into the inversion through a penalty function based on multiple probability density functions, where each probability density function represents a different lithology with distinct properties. We treat lithological units as clusters and use unsupervised K‐means clustering to separate the petrophysical information into different units of distinct lithologies that are not easily distinguishable. Through several synthetic examples, we demonstrate that the proposed framework leads full waveform inversion to elastic models that are superior to models obtained either without incorporating petrophysical information, or with a probabilistic penalty function based on a single probability density function.
Knockdown of GCN2 inhibits high glucose‐induced oxidative stress and apoptosis in retinal pigment epithelial cells
Authors: Zhang Xiaohui , He Na , Xing Yao , Lu Ye
Published: December 2019

Increasing evidence suggests that general control nonderepressible 2 (GCN2) is a critical regulator of oxidative stress and cell apoptosis in response to various stimuli. However, the role of GCN2 in diabetic retinopathy remains unclear. The aim of the present study was to investigate the effects of GCN2 on oxidative stress and apoptosis in ARPE‐19 cells exposed to high glucose. The results showed that GCN2 was highly expressed in high glucose‐induced ARPE‐19 cells. Moreover, knockdown of GCN2 greatly improved ARPE‐19 cell viability in response to high glucose. In addition, GCN2 knockdown significantly suppressed the production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased superoxide dismutase (SOD) activity in high glucose‐stimulated ARPE‐19 cells. Furthermore, GCN2 knockdown reduced cell apoptosis and enhanced the activation of nuclear factor E2‐related factor 2/heme oxygenase‐1 (Nrf2/HO‐1) pathway in high glucose‐stimulated ARPE‐19 cells. However, knockdown of Nrf2 reversed the effects of GCN2 on oxidative stress and cell apoptosis. Taken together, our findings suggest that knockdown of GCN2 inhibits high glucose‐induced oxidative stress and apoptosis in ARPE‐19 cells through activation of the Nrf2/HO‐1 pathway.
Three‐year surveillance (2016–2018) of chigger mites vector for tsutsugamushi disease in the Hwaseong‐Si area of Gyeonggi‐Do, Republic of Korea
Authors: Jun Hojong , Jegal Seung , Kim‐Jeon Myung‐Deok , Roh Jong Yul , Lee Wook‐Gyo , Park Seo Hye , Ahn Seong Kyu , Lee Jinyoung , Gong Young Woo , Kwon Mun Ju , Bahk Young Yil , Kim Tong‐Soo
Published: December 2019

Owing to climate change, the global resurgence of vector‐borne infectious diseases has emerged as a critical public health issue. Orientia tsutsugamushi is the etiological agent of tsutsugamushi disease (scrub typhus) a mite‐borne acute febrile disease occurring in the Asia‐Pacific region. We investigated the prevalence of tsutsugamushi disease transmitted by chigger mite vectors living on rodents. Using sticky‐type chigger traps for three months during 2016–2018, 1,057 chigger mites were collected (chigger mite index, 1.31) from four locations in the Hwaseong‐si area of Gyeonggi‐do, Republic of Korea. Five species distributed among three genera were identified. In addition, 94 rodents were captured (collection rate: 7.83%) using Sherman live traps over the course of three months (April, October, and November) during 2016–2017. Three rodent species were captured and identified and the striped field mouse (Apodemus agrarius) was the dominant rodent host species in the surveyed area. A total of 10,469 ectoparasitic chigger mites were recovered from the 94 rodents, from which 13 species distributed among four genera were identified. Of the 5,250 chigger mites examined, Leptotrombidium pallidum was most abundant (n = 2,558), followed by L. orientale, L. scutellare, L. zetum, Euschoengastia koreaensis, L. subintermedium, and Neotrombicula tamiyai. Of the examined chigger mites, no groups recovered from rodent hosts tested positive for O. tsutsugamushi. This study provides fundamental regional information on vector‐borne disease data collection in the Hwaseong‐si area, Gyeonggi‐do, and will further contribute to formulating disease control and prevention strategies.
The effects of feed materials on the nutrient composition of Protaetia brevitarsis larvae
Authors: Jeong Deokyeol , Min Namgyong , Kim Yeongbu , Kim Soo Rin , Kwon Ohseok
Published: December 2019

To find out the effect of feed materials on the nutrient composition of Protaetia brevitarsis larvae (Pbl), three different feed materials were prepared and fed to the Pbl populations. After the Pbl population reached the third instar stage, they were boiled and dried for the nutrient analysis. The results showed that the nutrient composition of Pbl varied in response to the feed materials. Therefore, it is critical to set a feed material standard to guarantee the efficacy of Pbl medicinal property.
Cryopyrin‐associated periodic fever syndrome in children: A case‐based review
Authors: Gupta Ayush , Tripathy Saroj Kumar , Phulware Ravi Hari , Arava Sudheer , Bagri Narendra Kumar
Published: December 2019

Cryopyrin‐associated periodic fever syndrome (CAPS) represents an increasingly recognized disease group entity, with varied presentations. CAPS includes 3 clinical entities, namely, familial cold‐induced autoinflammatory syndrome (FCAS; MIM #120100), Muckle‐Wells syndrome (MWS; MIM #191900) and chronic inflammatory neurologic cutaneous and articular syndrome (CINCA; MIM #607115); which share several overlapping clinical features. These patients often present with early‐onset episodes of fever and rash, and variable systemic signs and symptoms, making it a great mimicker of other systemic autoimmune diseases. The episodes are transient and related to exposure to cold temperature and worsen in the winter season. We hereby present a case presenting with recurrent seasonal fever and rash, diagnosed as FCAS/ MWS overlap based on clinical signs and symptoms and positive testing for NLRP3 gene mutation. We also discuss the clinical presentation and complications of CAPS, chiefly FCAS and MWS, along with the previously described pediatric cases of CAPS. We tried to review the complexities of management of such patients, including the genetic diagnosis and the role of biological therapy. Based on the review of the literature, given the evident broad spectrum of symptoms and signs, use of next‐generation sequencing can help in prompt diagnosis and early initiation of biological agents, which may play a great role in reducing the complications that these patients may experience in the long run.
The role of rhizodeposits in shaping rhizomicrobiome
Authors: Tian Tao , Reverdy Alicyn , She Qianxuan , Sun Bingbing , Chai Yunrong
Published: December 2019

Rhizomicrobiome, the communities of microorganisms surrounding the root of the plant, plays a vital role in promoting plant growth and health. The composition of rhizomicrobiome is dynamic both temporally and spatially, and is influenced greatly by the plant host and environmental factors. One of the key influencing factors is rhizodeposits, composed of root‐released tissue cells, exudates, lysates, volatile compounds, etc. Rhizodeposits are rich in carbon and nitrogen elements, and able to select and fuel the growth of rhizomicrobiome. In this minireview, we overview the generation, composition and dynamics of rhizodeposits, and discuss recent work describing the general and specific impacts of rhizodeposits on rhizomicrobiome. We focus further on root exudates, the most dynamic component of rhizodeposits, and review recent progresses about the influence of specific root exudates in promoting bacterial root colonization, inducing biofilm development, acting as plant defence and shaping the rhizomicrobiome.
The Role of AIIB in the ‘New Normal’ Era for Indonesia and ASEAN
Authors: Basri M. Chatib
Published: December 2019

History shows that trade and industrialization were the keys to economic development in East Asia and Southeast Asia. But situations change. The current rise in economic nationalism leads one to ask: Can Southeast Asian nations, including Indonesia, still use the old recipe of open trade and industrialization? Does economic cooperation still have a place? Against the backdrop of a changing trade environment and creeping protectionism under the Donald Trump US administration and amid lackluster global growth, the question that we must ask is, what can Indonesia and other Southeast Asian nations do given these conditions? This essay will specifically examine how the Asian Infrastructure Investment Bank (AIIB) can play a role in this situation. This essay argues that to overcome the anti‐globalization sentiment, it is necessary to create regional cooperation success stories from policies that are politically feasible and economically sound. There are several candidates for such success stories, including using the ASEAN Infrastructure Fund to develop ASEAN connectivity. The AIIB together with the ADB can play an important role here.
Comparative study of three types of lymphadenectomy along the left recurrent laryngeal nerve by minimally invasive esophagectomy
Authors: Zhang Shuangping , Zhang Peng , Guo Shiping , Lian Jianhong , Chen Yun , Chen Ailan , Ma Yong , Li Feng
Published: December 2019

Background

The objective of this study was to compare three kinds of lymphadenectomy methods along the recurrent laryngeal nerve (RLN) and assess the safety and effectiveness of the new method.

Methods

A total of 194 patients with esophageal cancer who underwent minimally invasive esophagectomy (MIE) at our institution from May 2013 to May 2017 were analyzed retrospectively. According to the method of lymphadenectomy along the left RLN, the patients were divided into three groups: 75 cases underwent the conventional method (A group), 80 cases the skeletonized method (B group) and 39 cases the modified Bascule method (C group). The number of dissected lymph nodes and surgical outcomes were recorded and compared to identify differences among the three groups.

Results

The frequency of metastasis to the LRLN lymph node was 18.6% among all patients, and 12%, 20% and 28% in groups A, B and C, respectively. The number of harvested lymph nodes (total/chest/LRLN/LRLN+) in group B and group C were significantly greater than that of group A, but not significant between group B and group C. The hoarseness rate in group C was 15.4%, which was lower than the rate in group B (21.3%) and higher than the rate in group A (13.3%), but there was no statistical significance.

Conclusions

The new method for lymphadenectomy along the left RLN during MIE in the semi‐prone position is safe and reliable. It provides sufficient lymph node dissection along the left RLN.
Castries Merchandising Inc.
Authors: Kalesnikoff Douglas , Hernik Michael
Published: December 2019

This two‐part case focuses on red flags of attempted earnings management for a St. Lucian company that is moving from 100 percent family‐owned to selling 50 percent of the family's shares to an equity fund. In order to increase the earnings growth rate in the three years leading up to the proposed sale to an equity fund in 2021, the earnings for the most recent three years (2016–2018) have been artificially depressed. The resulting byproduct of the earnings management is the underprovision of income taxes for the past three years, which is detected by the tax authorities in St. Lucia. The student assumes the role of a tax auditor for the tax authority in St. Lucia assigned to audit Castries Merchandising Inc. (CMI), a merchandiser of building products, hardware, and automobile parts. In Part 1 the student is provided excerpts of the financial statements of CMI with some anomalies that have been detected by a software program. In Part 2 the student is provided with further information of excerpts from the trial balance and an interview with the CFO, who is a member of the family ownership group of CMI and also a Canadian CPA registered in Ontario. Drawing on the student's knowledge of auditing, accounting principles, and financial statement analysis, the student's task is to both reassess the income taxes for the years 2016 to 2018 and contemplate how management may be manipulating the financial statements in order to benefit from the planned future sale of CMI's shares to an equity fund.
Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women
Authors: Drew T. , Balki M. , Farine D. , Ye X. Y. , Downey K. , Carvalho J. C. A.
Published: December 2019

Postpartum haemorrhage is a leading cause of maternal death during childbirth. There is an increasing incidence of atonic postpartum haemorrhage in developed countries, and maternal obesity has been proposed as a contributing factor. The dose–response relationship of carbetocin in obese women has not yet been determined. We conducted a double‐blind, dose‐finding study of carbetocin using a biased coin up‐and‐down design in women with a body mass index ≥ 40 kg.m−2 undergoing elective caesarean section. The determinant for a successful response was satisfactory uterine tone, with no intra‐operative need for additional uterotonic drugs. Secondary outcomes included the use of additional uterotonic drugs postoperatively, estimated blood loss and adverse effects of carbetocin administration. Thirty women were recruited to the study. The median (IQR [range]) body mass index was 44.93 (41.5–55.2 [40–66.5]) kg.m−2. The ED90 of carbetocin was estimated as 62.9 (95%CI 57.0–68.7) μg using the truncated Dixon and Mood method, and 68 (95%CI 52–77) μg using the isotonic regression method. The estimated blood loss was 880 (621–1178 [75–2442]) ml. The overall rates of hypotension and hypertension after delivery were 40% and 6.7%, respectively, while nausea occurred in 26.7% of women. The ED90 for carbetocin in obese women at elective caesarean section is lower than the dose of 100 μg currently recommended by the Society of Obstetricians and Gynaecologists of Canada, but is approximately four times higher than the previously demonstrated ED90 of 14.8 μg in women with body mass index < 40 kg.m−2.
Estimating treatment importance in multidrug‐resistant tuberculosis using Targeted Learning: An observational individual patient data network meta‐analysis
Authors: Wang Guanbo , Schnitzer Mireille E. , Menzies Dick , Viiklepp Piret , Holtz Timothy H. , Benedetti Andrea
Published: December 2019

Persons with multidrug‐resistant tuberculosis (MDR‐TB) have a disease resulting from a strain of tuberculosis (TB) that does not respond to at least isoniazid and rifampicin, the two most effective anti‐TB drugs. MDR‐TB is always treated with multiple antimicrobial agents. Our data consist of individual patient data from 31 international observational studies with varying prescription practices, access to medications, and distributions of antibiotic resistance. In this study, we develop identifiability criteria for the estimation of a global treatment importance metric in the context where not all medications are observed in all studies. With stronger causal assumptions, this treatment importance metric can be interpreted as the effect of adding a medication to the existing treatments. We then use this metric to rank 15 observed antimicrobial agents in terms of their estimated add‐on value. Using the concept of transportability, we propose an implementation of targeted maximum likelihood estimation, a doubly robust and locally efficient plug‐in estimator, to estimate the treatment importance metric. A clustered sandwich estimator is adopted to compute variance estimates and produce confidence intervals. Simulation studies are conducted to assess the performance of our estimator, verify the double robustness property, and assess the appropriateness of the variance estimation approach.