bluuebunny/crossref_metadata_2025 huggingface dataset:
Arhgap25deficiency leads to decreased numbers of peripheral blood B cells and defective germinal center reactions
Authors: Lindner Silke E. , Egelston Colt A. , Huard Stephanie M. , Lee Peter P. , Wang Leo D.
Published: March 2020

Rho family GTPases are critical for normal B cell development and function and their activity is regulated by a large and complex network of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). However, the role of GAPs in B cell development is poorly understood. Here we show that the novel Rac-GAP ARHGAP25 is important for B cell development in mice in a CXCR4-dependent manner. We show thatArhgap25deficiency leads to a significant decrease in peripheral blood B cell numbers, as well as defects in mature B cell differentiation.Arhgap25-/-B cells respond to antigen stimulationin vitroandin vivobut have impaired germinal center formation and decreased IgG1 class switching. Additionally,Arhgap25-/-B cells exhibit increased chemotaxis to CXCL12. Taken together, these studies demonstrate an important role forArhgap25 in peripheral B cell development and antigen response.
Intraepithelial T cells diverge by intestinal location as pigs age
Authors: Wiarda Jayne E. , Trachsel Julian M. , Bond Zahra F. , Byrne Kristen A. , Gabler Nicholas K. , Loving Crystal L.
Published: March 2020

T cells resident within the intestinal epithelium play a central role in barrier integrity and provide a first line of immune defense. Intraepithelial T cells (IETs) are among the earliest immune cells to populate and protect intestinal tissues, thereby giving them an important role in shaping gut health early in life. In pigs, IETs are poorly defined, and their maturation in young pigs has not been well studied. Given the importance of IETs in contributing to early life and long-term intestinal health through interactions with epithelial cells, the microbiota, and additional environmental factors, a deeper characterization of IETs in pigs is warranted. The objective of this study was to analyze age- and intestinal location-dependent changes in IETs across multiple sites of the small and large intestine in pigs between 4 and 8 weeks of age. IETs increased in abundance over time and belonged to both γδ and αβ T cell lineages. Similar compositions of IETs were identified across intestinal sites in 4-week-old pigs, but compositions diverged between intestinal sites as pigs aged. CD2+CD8α+γδ T cells and CD4−CD8α+αβ T cells comprised >78% of total IETs at all intestinal locations and ages examined. Greater percentages of γδ IETs were present in large intestine compared to small intestine in older pigs. Small intestinal tissues had greater percentages of CD2+CD8α−γδ IETs, while CD2+CD8α+γδ IET percentages were greater in the large intestine. Percentages of CD4−CD8α+αβ IETs increased over time across all intestinal sites. Moreover, percentages of CD27+cells decreased in ileum and large intestine over time, indicating increased IET activation as pigs aged. Percentages of CD27+cells were also higher in small intestine compared to large intestine at later timepoints. Results herein emphasize 4 to 8 weeks of age as a critical window of IET maturation and suggest strong associations between intestinal location and age with IET heterogeneity in pigs.
An active chromatin interactome in relevant cell lines elucidates biological mechanisms at genetic risk loci for dermatological traits
Authors: Shi Chenfu , Ray-Jones Helen , Ding James , Duffus Kate , Fu Yao , Gaddi Vasanthi Priyadarshini , Gough Oliver , Hankinson Jenny , Martin Paul , McGovern Amanda , Yarwood Annie , Gaffney Patrick , Eyre Steve , Rattray Magnus , Warren Richard B , Orozco Gisela
Published: March 2020

Chromatin looping between regulatory elements and gene promoters presents a potential mechanism whereby disease risk variants affect their target genes. Here we use H3K27ac HiChIP, a method for assaying the active chromatin interactome in two cell lines: keratinocytes and skin derived CD8+ T cells. We integrate public datasets for a lymphoblastoid cell line and primary CD4+ T cells and identify gene targets at risk loci for skin-related disorders. Interacting genes enrich for pathways of known importance in each trait, such as cytokine response (psoriatic arthritis, psoriasis) and replicative senescence (melanoma). We show examples of how our analysis can inform changes in the current understanding of multiple psoriasis associated risk loci. For example, the variant rs10794648, which is generally assigned toIFNLR1, was linked toGRHL3in our dataset, a gene essential in skin repair and development. Our findings, therefore, indicate a renewed importance of skin related factors in the risk of disease.

Abstract Figure

Graphical Abstract

In this article we take disease associated variants from 5 dermatological conditions and use cell type specific datasets to map genes that could be affected by these variants, providing insight into disease mechanisms.
Resident and elicited macrophages differ in expression of their glycomes and lectins
Authors: Park Diane D. , Chen Jiaxuan , Kudelka Matthew R. , Jia Nan , Haller Carolyn A. , Kosaraju Revanth , Premji Alykhan M. , Galizzi Melina , Nairn Alison V. , Moreman Kelley W. , Cummings Richard D. , Chaikof Elliot L.
Published: March 2020

The pleiotropic functions of macrophages in immune defense, tissue repair, and maintenance of tissue homeostasis are supported by the heterogeneity in macrophage sub-populations that differ both in ontogeny and polarization. Although glycans and lectins are integral to macrophage function, little is known about the factors governing their expression. Here we show that the cellular glycome of murine peritoneal macrophages primarily reflects developmental origin and to a lesser degree, cellular polarization. Resident macrophages were characterized by a simple glycome, predominantly consisting of core 1 O-glycans, while elicited macrophages also expressed core 2 O-glycans, along with highly branched and extended complex-type N-glycans, that exhibited a higherN-acetylneuraminic acid:N-glycolylneuraminic acid ratio. Strikingly, our analysis revealed that resident and elicited macrophages express 139 lectin genes, with differential expression of 49 lectin genes, including galectins, Siglecs, and C-type lectins. These results suggest that regulation of self-glycan-protein complexes may be central to macrophage residence and recruitment.
Active Vision in Immersive, 360° Real-World Environments
Authors: Haskins Amanda J. , Mentch Jeff , Botch Thomas L. , Robertson Caroline E.
Published: March 2020

Vision is an active process. Humans actively sample their sensory environment via saccades, head turns, and body movements. Yet, little is known about active visual processing in real-world environments. Here, we exploited recent advances in immersive virtual reality (VR) and in-headset eye-tracking to show that active viewing conditions impact how humans process complex, real-world scenes. Specifically, we used quantitative, model-based analyses to compare which visual features participants prioritize over others while encoding a novel environment in two experimental conditions: active and passive. In the active condition, participants used head-mounted VR displays to explore 360º scenes from a first-person perspective via self-directed motion (saccades and head turns). In the passive condition, 360º scenes were passively displayed to participants within the VR headset while they were head-restricted. Our results show that signatures of top-down attentional guidance increase in active viewing conditions: active viewers disproportionately allocate their attention to semantically relevant scene features, as compared with passive viewers. We also observed increased signatures of exploratory behavior in eye movements, such as quicker, more entropic fixations during active as compared with passive viewing conditions. These results have broad implications for studies of visual cognition, suggesting that active viewing influences every aspect of gaze behavior – from the way we move our eyes to what we choose to attend to – as we construct a sense of place in a real-world environment.

Significance Statement

Eye-tracking in immersive virtual reality offers an unprecedented opportunity to study human gaze behavior under naturalistic viewing conditions without sacrificing experimental control. Here, we advanced this new technique to show how humans deploy attention as they encode a diverse set of 360º, real-world scenes, actively explored from a first-person perspective using head turns and saccades. Our results build on classic studies in psychology, showing that active, as compared with passive, viewing conditions fundamentally alter perceptual processing. Specifically, active viewing conditions increase information-seeking behavior in humans, producing faster, more entropic fixations, which are disproportionately deployed to scene areas that are rich in semantic meaning. In addition, our results offer key benchmark measurements of gaze behavior in 360°, naturalistic environments.
Discriminating the Influence of Correlated Factors from Multivariate Observations: the Back-to-Back Regression
Authors: King Jean-Rémi , Charton François , Lopez-Paz David , Oquab Maxime
Published: March 2020

Identifying causes solely from observations can be particularly challenging when i) potential factors are difficult to manipulate independently and ii) observations are multi-dimensional. To address this issue, we introduce “Back-to-Back” regression (B2B), a linear method designed to efficiently measure, from a set of correlated factors, those that most plausibly account for multidimensional observations. First, we prove the consistency of B2B, its links to other linear approaches, and show how it provides a robust, unbiased and interpretable scalar estimate for each factor. Second, we use a variety of simulated data to show that B2B outperforms least-squares regression and cross-decomposition techniques (e.g. canonical correlation analysis and partial least squares) on causal identification when the factors and the observations are partially collinear. Finally, we apply B2B to magneto-encephalography of 102 subjects recorded during a reading task to test whether our method appropriately disentangles the respective contribution of word length and word frequency - two correlated factors known to cause early and late brain responses respectively. The results show that these two factors are better disentangled with B2B than with other standard techniques.
Parallelism in gene expression between foothill and alpine ecotypes inArabidopsis arenosa
Authors: Wos Guillaume , Bohutínská Magdalena , Nosková Jana , Mandáková Terezie , Kolář Filip
Published: March 2020

Parallel adaptation results from independent evolution of similar traits between closely related lineages and allows testing to which extent evolution is repeatable. Parallel adaptation often involves similar gene expression changes but the identity of genes shaped by parallel selection and the causes of expression parallelism remains largely unknown. By comparing genomes and transcriptomes of four independent foothill–alpine population pairs across four treatments, we addressed genetic basis, plasticity and functional consequences of gene expression parallelism in alpine adaptation. Seeds of four population pairs ofArabidopsis arenosafrom distinct mountain regions were raised under four treatments that differed in temperature and irradiance, factors varying strongly with elevation. Parallelism in gene expression was quantified by RNA-seq in leaves of young plants. By manipulating temperature and irradiance, we also tested for parallelism in plasticity (gene-by-environment interaction [GEI]). We found significant parallelism in differential gene expression across four independently recruited alpine ecotypes with an overrepresentation of genes involved in biotic stress response. In addition, we demonstrated significant parallelism in GEI indicating shared response to environmental variation in our foothill and alpine populations. Fraction of genes showing expression parallelism also encompassed genomic variants showing outlying differentiation, with greater enrichment of such variants in cis-regulatory elements. In summary, our results suggest frequent evolutionary repeatability in shaping expression difference associated with colonization of an alpine environment and support the hypothesis of an important role of genetic variation in cis-regulatory elements in gene expression parallelism.
Root-derivedtrans-zeatin cytokinin protectsArabidopsisplants against photoperiod stress
Authors: Frank Manuel , Cortleven Anne , Novak Ondrej , Schmülling Thomas
Published: March 2020

Recently, a novel type of abiotic stress caused by a prolongation of the light period - coined photoperiod stress - has been described inArabidopsis. During the night after the prolongation of the light period, stress and cell death marker genes are induced. The next day, strongly stressed plants display a reduced photosynthetic efficiency and leaf cells eventually enter programmed cell death. The phytohormone cytokinin (CK) acts as a negative regulator of this photoperiod stress syndrome. In this study, we show thatArabidopsiswild-type plants increase the CK concentration in response to photoperiod stress. Analysis of cytokinin synthesis and transport mutants revealed that root-derivedtrans-zeatin (tZ)-type CKs protect against photoperiod stress. The CK signaling proteins ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 2 (AHP2), AHP3 and AHP5 and transcription factors ARABIDOPSIS RESPONSE REGULATOR 2 (ARR2), ARR10 and ARR12 are required for the protective activity of CK. Analysis of higher order B-typearrmutants suggested that a complex regulatory circuit exists in which the loss ofARR10orARR12can rescue thearr2phenotype. Together the results revealed the role of root-derived CK acting in the shoot through the two-component signaling system to protect from the negative consequences of strong photoperiod stress.
Dentate gyrus population activity during immobility supports formation of precise memories
Authors: Pofahl Martin , Nikbakht Negar , Haubrich André N. , Nguyen Theresa , Masala Nicola , Braganza Oliver , Macke Jakob H. , Ewell Laura A. , Golcuk Kurtulus , Beck Heinz
Published: March 2020

The hippocampal dentate gyrus is an important relay conveying sensory information from the entorhinal cortex to the hippocampus proper. During exploration, the dentate gyrus has been proposed to act as a pattern separator. However, the dentate gyrus also shows structured activity during immobility and sleep. The properties of these activity patterns at cellular resolution, and their role in hippocampal-dependent memory processes have remained unclear. Using dual-color in-vivo two-photon Ca2+imaging, we show that in immobile mice dentate granule cells generate sparse, synchronized activity patterns associated with entorhinal cortex activation. These population events are structured and modified by changes in the environment; and they incorporate place- and speed cells. Importantly, they recapitulate population patterns evoked during self-motion. Using optogenetic inhibition during immobility, we show that granule cell activity during immobility is required to form dentate gyrus-dependent spatial memories. These data suggest that memory formation is supported by dentate gyrus replay of population codes of the current environment.
Mycobacterium tuberculosisFasR senses long fatty acyl-CoA through a tunnel, inducing DNA-dissociation via a transmission spine
Authors: Lara Julia , Diacovich Lautaro , Trajtenberg Felipe , Larrieux Nicole , Malchiodi Emilio L. , Fernandez Marisa M. , Gago Gabriela , Gramajo Hugo , Buschiazzo Alejandro
Published: March 2020

Mycobacterium tuberculosisis a pathogen with a unique cell envelope including very long fatty acids, implicated in bacterial resistance and host immune modulation. FasR is a two-domain transcriptional activator that belongs to the TetR family of regulators, and plays a central role in mycobacterial long-chain fatty acyl-CoA sensing and lipid biosynthesis regulation. We now disclose crystal structures ofM. tuberculosisFasR in complex with acyl effector ligands and with DNA, uncovering its sensory and switching mechanisms. A long tunnel traverses the entire effector-binding domain, enabling long fatty acyl effectors to bind. Only when the tunnel is entirely occupied, the protein dimer adopts a rigid configuration, with its DNA-binding domains in an open state that leads to DNA dissociation. Structure-guided point-mutations further support this effector-dependent mechanism. The protein-folding hydrophobic core, connecting the two domains, is completed by the effector ligand into a continuous spine, explaining the allosteric flexible-to-ordered transition. The transmission spine is conserved in all TetR-like transcription factors, offering new opportunities for anti-tuberculosis drug discovery.
The paradoxical effects of K+channel gain-of-function are mediated by GABAergic neuron hypoexcitability and hyperconnectivity
Authors: Shore Amy N. , Colombo Sophie , Tobin William F. , Petri Sabrina , Cullen Erin R. , Dominguez Soledad , Bostick Christopher D. , Beaumont Michael A. , Williams Damian , Khodagholy Dion , Yang Mu , Lutz Cathleen M. , Peng Yueqing , Gelinas Jennifer N. , Goldstein David B. , Boland Michael J. , Frankel Wayne N. , Weston Matthew C.
Published: March 2020

Gain-of-function (GOF) variants in K+channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K+currents lead to network hyperexcitability. Here, we introduced a human Na+-activated K+(KNa) channel variant (KCNT1-Y796H) into mice and, using a multiplatform approach, found motor cortex hyperexcitability and early-onset seizures, phenotypes strikingly similar to those of human patients. Although the variant increased KNacurrents in cortical excitatory and inhibitory neurons, there was a selective increase in the KNacurrent across subthreshold voltages in inhibitory neurons, particularly in those with non-fast spiking properties, resulting in impaired excitability and AP generation. We further observed evidence of synaptic rewiring associated with hyperexcitable networks, including increases in homotypic synaptic connectivity and the ratio of excitatory-to-inhibitory synaptic input. These findings support inhibitory neuron-specific mechanisms in mediating the epileptogenic effects of K+channel GOF, offering cell-type-specific currents and effects as promising targets for therapeutic intervention.

GRAPHICAL ABSTRACT
Mesophilic enzyme function at high temperature: molecular dynamics of hyperthermophilic and mesophilic pyrophosphatases
Authors: Agarwal Rupesh , Shrestha Utsab R. , Chu Xiang-Qiang , Petridis Loukas , Smith Jeremy C.
Published: March 2020

The mesophilic inorganic pyrophosphatase fromEscherichia coli(EcPPase) retains function at 353 K, the physiological temperature of hyperthermophilicThermoccoccus thioreducens, whereas, the homolog protein from the hyperthermophilic organism (TtPPase) cannot function at room temperature. To explain this asymmetric behavior, we examined structural and dynamical properties of the two proteins using molecular dynamics simulations. The global flexibility ofTtPPase is significantly higher than its mesophilic homolog at all tested temperature/pressure conditions. However, at 353 K,EcPPase reduces its solvent-exposed surface area and increases subunit compaction while maintaining flexibility in its catalytic pocket. In contrast,TtPPase lacks this adaptability and has increased rigidity and reduced protein:water interactions in its catalytic pocket at room temperature, providing a plausible explanation for its inactivity near room temperature.
Ancestry adjustment improves genome-wide estimates of regional intolerance
Authors: Hayeck Tristan J. , Stong Nicholas , Baugh Evan , Dhindsa Ryan , Turner Tychele N. , Malakar Ayan , Mosbruger Timothy L. , Duan Yuncheng , Ionita-Laza Iuliana , Goldstein David , Allen Andrew S.
Published: March 2020

Genomic regions subject to purifying selection are more likely to carry disease causing mutations. Cross species conservation is often used to identify such regions but has limited resolution to detect selection on short evolutionary timescales such as that occurring in only one species. In contrast, intolerance looks for depletion of variation relative to expectation within a species, allowing species specific features to be identified. When estimating the intolerance of noncoding sequence methods strongly leverage variant frequency distributions. As the expected distributions depend on demography, if not properly controlled for, ancestral population source may obfuscate signals of selection. We demonstrate that properly incorporating demography in intolerance estimation greatly improved variant classification (13% increase in AUC relative to comparison constraint test, CDTS; and 9% relative to conservation). We provide a genome-wide intolerance map that is conditional on demographic history that is likely to be particularly valuable for variant prioritization.
Medial temporal atrophy in preclinical dementia: visual and automated assessment during six year follow-up
Authors: Mårtensson Gustav , Håkansson Claes , Pereira Joana B. , Palmqvist Sebastian , Hansson Oskar , van Westen Danielle , Westman Eric
Published: March 2020

Abstract

Medial temporal lobe (MTL) atrophy is an important morphological marker of many dementias and is closely related to cognitive decline. In this study we aimed to characterize longitudinal progression of MTL atrophy in 93 individuals with subjective cognitive decline and mild cognitive impairment followed up over six years, and to assess if clinical rating scales are able to detect these changes. All MRI images were visually rated according to Scheltens’ scale of medial temporal atrophy (MTA) by two neuroradiologists and AVRA, a software for automated MTA ratings. The images were also segmented using FreeSurfer’s longitudinal pipeline in order to compare the MTA ratings to volumes of the hippocampi and inferior lateral ventricles. We found that MTL atrophy rates increased with CSF biomarker abnormality, used to define preclinical stages of Alzheimer’s Disease. Both AVRA’s and the radiologists’ MTA ratings showed a similar longitudinal trajectory as the subcortical volumes, suggesting that visual rating scales provide a valid alternative to automatic segmentations. While the MTA scores from each radiologist showed strong correlations to subcortical volumes, the inter-rater agreement was low. We conclude that the main limitation of quantifying MTL atrophy with visual ratings in clinics is the subjectiveness of the assessment.
Human TRPA1 is an inherently mechanosensitive bilayer-gated ion channel
Authors: Moparthi Lavanya , Zygmunt Peter M.
Published: March 2020

The Transient Receptor Potential Ankyrin 1 (TRPA1) channel is an intrinsic chemo- and thermo-sensitive ion channel with distinct sensory signaling properties. Although a role of TRPA1 in mammalian mechanosensory transductionin vivoseems likely, it remains to be shown that TRPA1 has the inherent capability to respond to mechanical stimuli. Here we have used the patch-clamp technique to study the response of human purified TRPA1 (hTRPA1), reconstituted into artificial lipid bilayers, to changes in bilayer pressure. We report that hTRPA1 responded with increased single-channel open probability (Po) within the applied pressure interval of 7.5 to 60 mmHg with a half maximum Po(P50) value of 38.0 ± 2.3 mmHg. The Povalue reached a maximum close to 1 (0.87 ± 0.02) at 60 mmHg. Within the same pressure interval, hTRPA1 without its N-terminal ankyrin repeat domain (Δ1-688 hTRPA1) responded fully opened (0.99 ± 0.01) at 60 mmHg and with a P50value of 39.0 ± 1.1 mmHg. The pressure-evoked responses of hTRPA1 and Δ1-688 hTRPA1 at 45 mmHg were inhibited by the TRPA1 antagonist HC030031, and the activity of purified hTRPA1 at 45 mmHg was abolished by the thiol reducing agent tris(2-carboxyethyl)phosphine (TCEP). In conclusion, hTRPA1 is an inherent mechanosensitive ion channel gated by force-from-lipids. The hTRPA1 mechanosensitivity is dependent on the redox environment, and it is suggested that oxidative stress shifts hTRPA1 into a protein conformation sensitive to mechanical stimuli.
EYES ABSENT and TIMELESS integrate photoperiodic and temperature cues to regulate seasonal physiology inDrosophila
Authors: Abrieux Antoine , Xue Yongbo , Cai Yao , Lewald Kyle M. , Nhu Nguyen Hoang , Zhang Yong , Chiu Joanna C.
Published: March 2020

Organisms possess photoperiodic timing mechanisms to anticipate variations in day length and temperature as the seasons progress. The nature of the molecular mechanisms interpreting and signaling these environmental changes to elicit downstream neuroendocrine and physiological responses are just starting to emerge. Here, we demonstrate that inDrosophila melanogaster, EYES ABSENT (EYA) acts as a seasonal sensor by interpreting photoperiodic and temperature changes to trigger appropriate physiological responses. We observed that tissue-specific genetic manipulation ofeyaexpression is sufficient to disrupt the ability of flies to sense seasonal cues, thereby altering the extent of female reproductive dormancy. Specifically we observed that EYA proteins, which peak at night in short photoperiod and accumulate at higher levels in the cold, promote reproductive dormancy in femaleD. melanogaster. Furthermore, we provide evidence indicating that the role of EYA in photoperiodism and temperature sensing is aided by the stabilizing action of the light-sensitive circadian clock protein TIMELESS (TIM). We postulate that increased stability and level of TIM at night under short photoperiod together with the production of cold-induced and light-insensitive TIM isoforms facilitate EYA accumulation in winter conditions. This is supported by our observations thattimnull mutants exhibit reduced incidence of reproductive dormancy in simulated winter conditions, while flies overexpressingtimshow an increased incidence of reproductive dormancy even in long photoperiod.

Significance Statement

Extracting information on calendar time from seasonal changes in photoperiod and temperature is critical for organisms to maintain circannual cycles in physiology and behavior. Here we found that in flies, EYES ABSENT (EYA) protein act as a seasonal sensor by adjusting its abundance and circadian phase in response to changes in photoperiod and temperature. We show that the manipulation of EYA levels is sufficient to impair the ability of femaleDrosophilato regulate seasonal variation in reproductive dormancy. Finally, our results suggest an important role of the circadian clock protein TIMELESS (TIM) in modulating EYA level through its ability to measure night length, linking the circadian clock to seasonal timing.
Detection of HER2 expression and its structural alterations in gastric cancer tissues infected with cagA+H. pylori
Authors: Srivastava Akhileshwar Kumar , Singh Divya
Published: March 2020

Background

Helicobacter pylori(HP) cagA is the causing agent for development of gastric cancer (GC).H. pylorialso involves to trigger the EGFR (epidermal growth factor receptor) expression in gastric cancer cells. However, the prognostic relation of cagA with HER2 status in GC was not well understood.

Objective

The main aim of this study was to investigate the link of HER2 expression with CagA+H. pyloriin GC tissues.

Materials and Methods

The study was performed on 85 GC tissues of GC patients. The specific primers of 16S rDNA and cagA for PCR amplification were used. For investigation of HER2 status in GC tissues, immunohistochemistry and PCR amplification were performed. In silico study was performed for the investigation of interactive potential of HER2 with CagA protein.

Results

PCR amplified the 54 (63.52 %) of 85 GC tissues for HP that showed 34 (62.96 %) cagA+ HP. Immunohistochemistry of tissues revealed 57 (67.05 %) diffuse and 28 (32.94 %) intestinal type cancer. Of 85 cases, 21 GC tissues scored (2 + or 3 +) for positive HER2 expression and score (0 or 1 +) of 64 (75.29 %) showed negative. Of 21 HER2 + GC tissue, 15 biopsies had cagA+ HP and 2 were negative. PCR amplified single amplicon in 17 (20 %) CagA+ tissues and 3 (5.55 %) in CagA - HP. The molecular interactions of CagA was also showed its efficiency for HER2 expression.

Conclusion

The study concluded that CagA+ HP may induce HER2 overexpression in GC tissues.
Dataset Augmentation Allows Deep Learning-Based Virtual Screening To Better Generalize To Unseen Target Classes, And Highlight Important Binding Interactions
Authors: Scantlebury Jack , Brown Nathan , Von Delft Frank , Deane Charlotte M.
Published: March 2020

Current deep learning methods for structure-based virtual screening take the structures of both the protein and the ligand as input but make little or no use of the protein structure when predicting ligand binding. Here we show how a relatively simple method of dataset augmentation forces such deep learning methods to take into account information from the protein. Models trained in this way are more generalisable (make better predictions on protein-ligand complexes from a different distribution to the training data). They also assign more meaningful importance to the protein and ligand atoms involved in binding. Overall, our results show that dataset augmentation can help deep learning based virtual screening to learn physical interactions rather than dataset biases.

Graphical TOC Entry
Choices Change the Temporal Weighting of Decision Evidence
Authors: Talluri Bharath Chandra , Urai Anne E. , Bronfman Zohar Z. , Brezis Noam , Tsetsos Konstantinos , Usher Marius , Donner Tobias H.
Published: March 2020

Decisions do not occur in isolation, but are embedded in sequences of other decisions, often pertaining to the same source of evidence. Here, we characterized the impact of intermittent choices on the accumulation of a protracted stream of decision-relevant evidence towards a final decision. Human participants performed two versions, based on perceptual or numerical evidence, of a decision task that required two successive judgments at different times during the evidence stream: an intermittent response consisting of a binary choice, and a continuous estimation at the end of the evidence stream. In a control condition, subjects executed a choice-independent motor response instead of binary choice as the intermittent response. In both, perceptual and numerical tasks, the intermittent choice reduced the sensitivity of subsequent evidence, and flipped the relative temporal weighting of early and late evidence in the final estimation judgment. The individual extent of the choice-induced overall (non-selective) sensitivity reduction predicted the extent of the selective down-weighting of subsequent evidence inconsistent with the initial choice, a form of confirmation bias. In sum, active decisions about a protracted evidence stream profoundly alter the dynamics of evidence accumulation, consistent with an active, modulatory mechanism triggered by the choice.
Alternative paradigms for sustainability: a Relational worldview
Authors: Kennedy Ann-Marie , McGouran Cathy , Kemper Joya A.
Published: March 2020

Purpose

The authors do not claim that the following represents the views of any one tribe but instead the culmination of the academic literature written on the topic. Marketing’s current Western dominant social paradigm (DSP) is said to perpetuate “green”, yet unsustainable practices. The DSP does not support strictly pro-environmental practices and its proposed alternative, the new environmental paradigm (NEP), lacks in-depth conceptualisation, especially concerning business and marketing activities. However, the two paradigms contrast so much that a shift from one to the other is vehemently argued against and conceptually rife with problems. This paper aims to expand upon the merits of the NEP using indigenous people’s environmental philosophies [1] – as examples of historically supported and successful sustainable philosophies. It conceptualises a Relational view to provide a more practical alternative to the DSP and includes propositions for marketing implementation of this perspective.

Findings

By explicating both the DSP and NEP and reflecting on each through an indigenous Māori view, this paper provides propositions for a broadened paradigm that supports sustainability and its application for sustainable marketing.

Research limitations/implications

The implications of this research are in the area of paradigm development and in providing an alternative paradigm to that of the DSP. This paper is the first to fully explicate parts of the NEP and considers a solution to the problems of changing the current DSP so drastically by broadening the NEP using a Relational worldview.

Practical implications

The propositions and examples provided in this work give practical application of the newly presented paradigm for marketers influenced by indigenous belief systems.

Originality/value

This paper is the first to explicate parts of the NEP and broaden its reach by integrating a Relational worldview as an alternative to drastically changing the current DSP. It does so by proposing that marketers embrace a middle ground that is influenced by indigenous belief systems.
An integrated three-layered foresight framework
Authors: van Dorsser Cornelis , Taneja Poonam
Published: March 2020

Purpose

The paper aims to present an integrated foresight framework and method to support decision-makers who are confronted with today’s complex and rapidly changing world. The method aims at reducing the degree of uncertainty by addressing the inertia or duration of unfolding trends and by placing individual trends in a broader context.

Design/methodology/approach

The paper presents a three-layered framework and method for assessing megatrends based on their inertia or duration. It suggests that if long-term trends and key future uncertainties are studied in conjunction at a meta-level and placed in a broader multi-layered framework of trends, it can result in new insights.

Findings

The application of the proposed foresight method helps to systematically place a wide range of unrelated trends and key uncertainties in the context of a broader framework of trends, thereby improving the ability to understand the inertia, direction and mutual interaction of these trends.

Research limitations/implications

The elaboration of identified trends and key uncertainties is partly case-specific and subject to interpretation. It is aimed at illustrating the potential use of the framework.

Practical implications

The paper presents a new approach that may, by itself or in combination with existing foresight methods, offer new means for anticipating future developments.

Social implications

The use of the proposed framework has potential to provide better insight in the complexity of today’s rapid-changing world and the major transitions taking place. It aims to result in sharper foresight by reducing epistemic uncertainty for decision-makers.

Originality/value

The paper demonstrates how megatrends, Kondratieff waves and century-long trends can be placed in an integrated framework and analysed in conjunction.
Entrepreneurs' behavioural competencies for internationalisation
Authors: Cortellazzo Laura , Bonesso Sara , Gerli Fabrizio
Published: March 2020

Purpose

The entrepreneur is the main decision-maker in small and medium-sized enterprises and is the principal force in the implementation of a firm's international strategy. Research has paid limited attention to the intangible aspects of human capital, namely behavioural competencies that may have an impact on the entrepreneur's ability to take advantage of international opportunities. This study addresses this gap, identifying the behavioural competencies that distinguish entrepreneurs who pursue a stronger internationalisation expansion beyond the European market.

Design/methodology/approach

A competency modelling process is implemented for a sample of Italian entrepreneurs. Data on behavioural competencies are obtained through the coding of behavioural event interviews administrated to the entrepreneurs. Export intensity is adopted as a performance criterion to classify the entrepreneurs.

Findings

Three behavioural competencies (change catalyst, teamwork and organisational learning orientation) emerged as more significantly activated by entrepreneurs who show a higher export intensity in the global market.

Research limitations/implications

The exploratory nature of the study, conducted in a small sample and in a specific geographical area, may reduce the generalisability of the findings.

Practical implications

Entrepreneurs can become aware of the behavioural competencies needed for the implementation of internationalisation processes. Additionally, training programmes can be designed to promote the development of these behaviours.

Originality/value

Bridging the literature on international entrepreneurship, cross-cultural studies and competency-based research, this study highlights the role of behavioural competencies in the internationalisation process from a micro level of analysis. This article proposes a competency framework that can be adopted to assess a broader portfolio of entrepreneurs' behaviours.
The impact of reverse logistics onto green supply chain competitiveness evidence from Serbian consumers
Authors: Aćimović Slobodan , Mijušković Veljko , Rajić Vesna
Published: March 2020

Purpose

The purpose of this paper is to explain what determines the influence of reverse logistics onto green supply chain competitiveness and to find out if that influence is always uniform.

Design/methodology/approach

The paper contains an empirical research conducted using a survey-based study, which encompassed a sample size of 228 participants and final consumers that have experience in buying/using products derived from the reverse logistics process.

Findings

The results indicate that the influence of reverse logistics onto green supply chain competitiveness is dependent on the product return option and is mainly negative with Serbian consumers, since the perceived quality of each of the three return options is considered to be inferior compared to new products.

Practical implication

The study's empirical results show the there is a generally negative perception among consumers regarding the perceived quality of each of the three product return options, thus directly questioning the general justification of using reverse logistics in Serbian business practice. That is a sign for Serbian managers to enhance their efforts to raise future awareness of the green initiatives importance among business partners, but also final consumers.

Originality/value

The study`s contribution is twofold: first, it helps to additionally test the established and known methodology created by Hazenet al.(2011), thus contributing to the practical dimension of international comparability concerning consumer perceptions. Second, the study adds to research by addressing the gap in practical surveys regarding the reverse logistics practices.
Entrepreneurial orientation in the hospitality industry: evidence from Tanzania
Authors: Njoroge Msafiri , Anderson Wineaster , Mossberg Lena , Mbura Omari
Published: March 2020

Purpose

The purpose of this study is to identify and validate indicators of entrepreneurial orientation (EO) in the hospitality industry, as well as to examine its dimensionality in the context of emerging economies with a specific focus on tourist hotels in Tanzania.

Design/methodology/approach

The study uses a mixed-method approach for data collection and analysis. The qualitative study involved 20 in-depth interviews with hotel managers. Based on interview insights, indicators of EO were identified and applied in contextualizing the study and develop the survey questionnaires. The second phase, which was quantitative in nature involved a survey of hotels (n = 346) in the Coastal and Northern tourist circuits of Tanzania for validation and generalization. The exploratory and confirmatory factor analyses were used to analyze the quantitative data.

Findings

EO in the studied context consists of proactive-risk-taking, innovativeness and competition approach. Hotels focus on proactive and risk-taking efforts concurrently, undertake wide-ranging acts; pursue bold and risk decisions in exploiting opportunities; being proactive on opportunity exploration but less emphasis on initiation speed on actions of competitors. Innovativeness focuses on providing quality services; standardization of services; product introduction; and technological advancements. Besides, the conventional dimensions, hotels use competition approach geared at extensive marketing; customer management; and flexibility in pricing based on competition. EO also exhibits multidimensionality with its dimensions exhibiting moderate-to-high correlations and with acceptable discriminant validity.

Practical implications

The study’s findings imply that EO and its respective indicators confirmed in western contexts are not necessarily a perfect reflection and applicable in the hospitality industry in emerging economies like Tanzania. Hospitality firms must be vigilant with contextual characteristics – economically, socially and culturally shaping entrepreneurial opportunities.

Originality/value

This study identifies and validates indicators of EO in the hospitality industry in emerging economies. Moreover, the study adds to the body of knowledge that EO in this context is also multidimensional in nature.
Corporate governance practice in the context of the political situation in South Africa over the last 25 years
Authors: Kana Suresh Parbhoo
Published: March 2020

Purpose

This study aims to demonstrate, with reference to developments in the four King Reports on Corporate Governance for South Africa, that institutional culture should be governed with the same rigour applied to other strategic assets to align the pluralistic interests of government, business and society.

Design/methodology/approach

Historical narrative and analysis.

Findings

Institutional culture should be governed with the same rigour and veracity as more traditional assets to align organisational purpose with political and social interests.

Originality/value

This is part of a special issue that looks at the contribution of the King Reports to governance globally.
Measuring performance in corporate environmental reporting in Nigeria
Authors: Iredele Oluwamayowa Olalekan
Published: March 2020

Purpose

The purpose of this study is to measure the current level of corporate environmental reporting (CER) in the developing economy of Nigeria. This is with a view to drive the effort of firms towards improving on the present practice. An attempt is made to also determine the extent to which the level of CER differs on account of firm characteristics.

Design/methodology/approach

The study used data for the top 40 companies on the Nigerian stock exchange as of 31 December 2017 based on market capitalization. The annual reports, company website and sustainability reports were the major sources of data. The paper used descriptive statistics and one-way analysis of variance to analyse data.

Findings

Despite the attempt to explore multiple sources in obtaining environmental information, empirical evidence from the present study confirms that the level of environmental reporting is low; most companies report environmental issues through the website. It further found an association between CER and firm size.

Practical implications

The findings will be of interest to policymakers and regulators on the need to regulate environmental reporting. Thus, motivating firms towards better environmental performance in Nigeria.

Originality/value

The paper extends environmental reporting research in Nigeria beyond the use of annual reports. It captured environmental information reported through the website and sustainability reports. It provides information on the current status in terms of quality and content of information reported. Finally, it found that firm size is a contingent factor for CER in Nigeria.
Application of a trait‐based species screening framework for vegetation restoration in a tropical coral island of China
Authors: Wang Chen , Zhang Hui , Liu Hui , Jian Shuguang , Yan Junhua , Liu Nan
Published: March 2020

Selecting suitable species for vegetation restoration presents a notable challenge for land managers and scientists. Recently developed trait‐based approaches may be an effective means of overcoming this challenge. However, we lack a trait‐based species screening model that can be used to select potential species for restoration of degraded ecosystems.

Here, we developed a species screening model based on quantitative trait‐based theory and a maximum entropy algorithm. The objective was to select more species that have comparable restoration abilities to the target species that have high survival rates for vegetation restoration based on species' functional traits. Thus, species diversity will be improved to facilitate restoration. We also developed a software platform that can be used to implement the model. We then applied our model and software platform to select species for restoration efforts in a tropical coral island which is part of Hainan Island, China.

As a prerequisite, we started with three target species which have high potential for restoring the island. Likewise, 66 non‐native species were selected as the potential species pool. For each species, we identified and measured 28 traits that are strongly associated with harsh environments. Harsh environments are those with drought stress, high temperatures, intensive UV radiation, lack of real soil and nutrients, and high salinity and alkalinity. Then, our software platform was used to run the species selection model. Finally, 12 out of 66 species being identified as suitable species for restoration.

We transplanted seedlings of all 66 species to the island to monitor seedlings survival. We found that the 12 species identified from our model had high survival rates, which ranged from 86% to 91%. In contrast, the mean survival rate for species not identified from our model was less than 40%. These results suggest that our species screening procedure was appropriate for selecting candidate species for use in vegetation restoration.

We show that by using species natural history information, as well as functional trait data, candidate species for restoration efforts can be successfully identified in a timely manner. Importantly, our proposed method is faster and less costly than more commonly used ‘trial‐and‐error’ method. The most time‐consuming aspect of our approach is the need to measure the functional traits of target and potential species. Ultimately, we provide a protocol for using functional traits to quickly select a large number of suitable species for restoring degraded ecosystems. We expect that this work will be important for future vegetation restoration efforts in tropical islands, and perhaps other ecosystems as well. We also expect that our model will help prevent the invasive species and promote specific ecosystem functions.

A free Plain Language Summary can be found within the Supporting Information of this article.