bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative drug susceptibility testing for M. tuberculosis using unassembled sequencing data and machine learning
Authors:   The CRyPTIC consortium, Lachapelle Alexander S
Published: September 2021

There remains a clinical need for better approaches to rapid drug susceptibility testing in view of the increasing burden of multidrug resistant tuberculosis. Binary susceptibility phenotypes only capture changes in minimum inhibitory concentration when these cross the critical concentration, even though other changes may be clinically relevant. We developed a machine learning system to predict minimum inhibitory concentration from unassembled whole-genome sequencing data for 13 anti-tuberculosis drugs. We trained, validated and tested the system on 10,859 isolates from the CRyPTIC dataset. Essential agreement rates (predicted MIC within one doubling dilution of observed MIC) were above 92% for first-line drugs, 91% for fluoroquinolones and aminoglycosides, and 90% for new and repurposed drugs, albeit with a significant drop in performance for the very few phenotypically resistant isolates in the latter group. To further validate the model in the absence of external MIC datasets, we predicted MIC and converted values to binary for an external set of 15,239 isolates with binary phenotypes, and compare their performance against a previously validated mutation catalogue, the expected performance of existing molecular assays, and World Health Organization Target Product Profiles. The sensitivity of the model on the external dataset was greater than 90% for all drugs except ethionamide, clofazimine and linezolid. Specificity was greater than 95% for all drugs except ethambutol, ethionamide, bedaquiline, delamanid and clofazimine. The proposed system can provide quantitative susceptibility phenotyping to help guide antimicrobial therapy, although further data collection and validation are required before machine learning can be used clinically for all drugs.
Long-term meditation training is associated with enhanced attention and stronger posterior cingulate – rostrolateral prefrontal cortex resting connectivity
Authors: Kral Tammi RA , Lapate Regina , Imhoff-Smith Ted , Patsenko Elena , Grupe Daniel W , Goldman Robin , Rosenkranz Melissa A , Davidson Richard J
Published: September 2021

Mindfulness meditation has been shown to increase resting state functional connectivity (rsFC) between the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC), which is thought to reflect improvements in attention to the present moment. However, prior research in long-term meditation practitioners lacked quantitative measures of attention that would provide a more direct behavioral correlate and interpretational anchor for PCC–DLPFC connectivity and was inherently limited by small sample sizes. Moreover, whether mindfulness meditation primarily impacts brain function locally, or impacts the dynamics of large-scale brain networks, remained unclear. Here, we sought to replicate and extend prior findings of increased PCC – DLPFC rsFC in a sample of 40 long-term meditators (average practice= 3759 hours) who also completed a behavioral assay of attention. In addition, we tested a network-based framework of changes in inter-regional connectivity by examining network-level connectivity. We found that meditators had stronger PCC-rostrolateral prefrontal cortex (PFC) rsFC, lower connector hub strength across the default mode network (DMN) relative to other functional networks, and better attention to task, compared to 124 meditation-naïve controls. Orienting attention positively correlated with PCC– rostrolateral PFC connectivity, and negatively correlated with DMN connector hub strength. These findings provide novel evidence that posterior cingulate – rostrolateral PFC rsFC may support attention orienting, consistent with a role for rostrolateral PFC in meta-cognitive background awareness that is a core component of mindfulness meditation training. Our results further demonstrate that long-term mindfulness meditation may improve attention and strengthen the underlying brain networks.
The polyol pathway is an evolutionarily conserved system for sensing glucose uptake
Authors: Sano Hiroko , Nakamura Akira , Yamane Mariko , Niwa Hitoshi , Nishimura Takashi , Araki Kimi , Takemoto Kazumasa , Ishiguro Kei-ichiro , Aoki Hiroki , Kojima Masayasu
Published: September 2021

Cells must adjust the expression levels of metabolic enzymes in response to fluctuating nutrient supply. For glucose, such metabolic remodeling is highly dependent on a master transcription factor ChREBP/MondoA. However, it remains elusive how glucose fluctuations are sensed by ChREBP/MondoA despite the stability of major glycolytic pathways. Here we show that in both flies and mice, ChREBP/MondoA activation in response to glucose ingestion depends on an evolutionarily conserved glucose-metabolizing pathway: the polyol pathway. The polyol pathway converts glucose to fructose via sorbitol. It has been believed that this pathway is almost silent, and its activation in hyperglycemic conditions has deleterious effects on human health. We show that the polyol pathway is required for the glucose-induced nuclear translocation of Mondo, a Drosophila homologue of ChREBP/MondoA, which directs gene expression for organismal growth and metabolism. Likewise, inhibition of the polyol pathway in mice impairs ChREBP’s nuclear localization and reduces glucose tolerance. We propose that the polyol pathway is an evolutionarily conserved sensing system for the glucose uptake that allows metabolic remodeling.
Condensin Compacts DNA in 15nm steps and Requires FACT for Extrusion on Chromatin
Authors: Sudhakar Swathi , Fisher Gemma LM , Gutierrez-Escribano Pilar , Garcia-Luis Jonay , Cawood Christopher , Aragon Luis , Rueda David S
Published: September 2021

The authors have withdrawn this manuscript after detecting issues with two of the figures in the manuscript. Therefore, the authors do not wish this work to be cited as a reference. If you have any questions, please contact the corresponding authors.
NLRP3 activation in response to disrupted endocytic traffic
Authors: Lee Bali , Hoyle Christopher , Green Jack P. , Wellens Rose , Martin-Sanchez Fatima , Williams Daniel , Seoane Paula I. , Bennett Hayley , Adamson Antony , Lopez-Castejon Gloria , Lowe Martin , Brough David
Published: September 2021

Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and with a poorly defined regulation by sub-cellular organelles. Here, we tested the hypothesis that NLRP3 senses disrupted endosome trafficking to trigger inflammasome formation and inflammatory cytokine secretion. NLRP3-activating stimuli disrupted endosome trafficking and triggered localization of NLRP3 to vesicles positive for endosome markers and the inositol lipid PtdIns4P. Chemical disruption of endosome trafficking sensitized macrophages to the NLRP3 activator imiquimod driving enhanced inflammasome activation and cytokine secretion. Together these data suggest that NLRP3 is capable of sensing disruptions in the trafficking of endosomal cargoes, and that this may explain in part the spatial activation of the NLRP3 inflammasome complex. These data highlight new mechanisms amenable for the therapeutic targeting of NLRP3.

One-Sentence Summary

NLRP3 senses disruptions in endosome trafficking to trigger the formation of an inflammasome complex and initiate an inflammatory response.
Physical geography, isolation by distance and environmental variables shape genomic variation of wild barley (Hordeum vulgare L. ssp. spontaneum) in the Southern Levant
Authors: Chang Che-Wei , Fridman Eyal , Mascher Martin , Himmelbach Axel , Schmid Karl
Published: September 2021

Determining the extent of genetic variation that reflects local adaptation in crop wild relatives is of interest to discovering useful genetic diversity for plant breeding. We investigated the association of genomic variation with geographical and environmental factors in wild barley (Hordeum vulgare L. ssp. spontaneum) populations of the Southern Levant using genotyping-by-sequencing (GBS) of 244 accessions of the Barley1K+ collection. Inference of population structure resulted in four genetic clusters that corresponded to eco-geographical habitats and a significant association of lower gene flow rates with geographical barriers, e.g. the Judaean Mountains and the Sea of Galilee. Redundancy analysis (RDA) revealed that spatial autocorrelation explained 45% and environmental variables explained 15% of total genomic variation. Only 4.5% of genomic variation was exclusively attributed to environmental variation if the component confounded with spatial autocorrelation was excluded. A synthetic environmental variable combining latitude, solar radiation, and accumulated precipitation explained the highest proportion of genomic variation (3.9%). After correcting for population structure, soil water capacity was the most important environmental variable explaining 1.18% of genomic variation. Genome scans with outlier analysis and genome-environment association studies were conducted to identify signatures of adaptation. RDA and outlier methods jointly detected selection signatures in the pericentromeric regions of chromosome 3H, 4H, and 5H, but they mostly disappeared after correction for population structure. In conclusion, adaptation to the highly diverse environments of the Southern Levant over short geographical ranges has a small effect on the genomic diversity of wild barley highlighting the importance of non-selective forces in genetic differentiation.
Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice
Authors: Vaughan Owen R. , Rosario Fredrick J. , Chan Jeannie , Cox Laura A. , Ferchaud-Roucher Veronique , Zemski-Berry Karin A. , Reusch Jane E.B. , Keller Amy C. , Powell Theresa L. , Jansson Thomas
Published: September 2021

Obesity in pregnant women causes fetal cardiac dysfunction and increases offspring cardiovascular disease risk but its effect on myocardial metabolism is unknown. We hypothesised that maternal obesity alters fetal cardiac expression of metabolism-related genes and shifts offspring myocardial substrate preference from glucose towards lipids. Female mice were fed control or obesogenic diets before and during pregnancy. Fetal hearts were studied in late gestation (embryonic day, E18.5; term≈E21) and offspring were studied at 3, 6, 9 or 24 months postnatally. Maternal obesity increased heart weight and peroxisome proliferator activated receptor γ (Pparg) expression in female and male fetuses and caused left ventricular diastolic dysfunction in the adult offspring. Cardiac dysfunction progressively worsened with age in female, not male, offspring of obese dams, compared to age-matched controls. In 6-month-old offspring, exposure to maternal obesity increased cardiac palmitoyl carnitine-supported mitochondrial respiration in males and reduced myocardial 18F-fluorodeoxyglucose uptake in females. Cardiac Pparg expression remained higher in adult offspring of obese than control dams and correlated with contractile and metabolic function. Maternal obesity did not affect cardiac palmitoyl carnitine respiration in females or 18F-fluorodeoxyglucose uptake in males, or alter cardiac 3H-oleic acid uptake, pyruvate respiration, lipid content or fatty acid/glucose transporter abundance in offspring of either sex. The results support our hypothesis and show that maternal obesity affects offspring cardiac metabolism in a sex-dependent manner. Persistent upregulation of Pparg expression in response to overnutrition in utero may mechanistically underpin programmed cardiac impairments and contribute to cardiovascular disease risk in children of women with obesity.
Effect of Endoplasmic Reticulum Stress on Human Trophoblast Cells: Survival Triggering or Catastrophe Resulting in Death
Authors: Garip Gurur , Ozdil Berrin , Calik-Kocaturk Duygu , Oltulu Fatih , Eroglu Fatma Zuhal , Aktug Huseyin , Uysal Aysegul
Published: September 2021

Although in vitro endoplasmic reticulum (ER) stress studies have been carried out using Tunicamycin in human trophoblast cell lines in recent years, the effect of calcium homeostasis impaired by the effect of Thapsigargin on cell survival - death pathways have not been clearly demonstrated.

Here, the effects of ER stress and impaired calcium homeostasis on cell death pathways such as apoptosis and autophagy in 2-dimensional and 3-dimensional cell cultures were investigated using the HTR8 / SVneo cell line representing human trophoectoderm cells and the ER stressor Thapsigargin. By using Real Time PCR, gene and immunofluorescence analyzes were studied at the protein level.

In this study, it has been established that the Thapsigargin creates ER stress by increasing the level of GRP78 gene and protein in 2 and 3 dimensions of human trophoectoderm cells and that cells show different characterization properties in 2 and 3 dimensions. It has been determined that while it moves in the direction of EIF2A and IRE1A mechanisms in 2 dimensions, it proceeds in the direction of EIF2A and ATF6 mechanisms in 3 dimensions and creates different responses in survival and programmed cell death mechanisms such as apoptosis and autophagy.

With forthcoming studies, it is thought that the effects of Thapsigargin on the intrinsic pathway of apoptosis and the linkage of the autophagy mechanism, the examination of the survival-death pathways in the co-culture model with endometrial cells, therapeutic target molecules that will contribute to the elucidation of intracellular cell dynamics may increase the success of implantation.
Conserved induction of distinct antiviral signalling kinetics by primate interferon lambda 4 proteins
Authors: Guo Cuncai , Reuss Dorothee , Coey Jonathon D. , Sukumar Swathi , Lang Benjamin , McLauchlan John , Boulant Steeve , Stanifer Megan L. , Bamford Connor G. G.
Published: September 2021

Interferon lambdas (IFNλ) (also known as type III IFNs) are critical cytokines that combat infection predominantly at barrier tissues, such as the lung, liver and gastrointestinal tract. Humans have four IFNλs (1-4) where IFNλ1-3 show ∼80-95% homology and IFNλ4 is the most divergent displaying only ∼30% sequence identity. Variants in IFNλ4 in humans are associated with the outcome of infection, such as with hepatitis C virus. However, how IFNλ4 variants impact cytokine signalling in other tissues and how well this is conserved is largely unknown. In this study we address whether differences in antiviral signalling exist between IFNλ4 variants in human hepatocyte and intestinal cells, comparing them to IFNλ3. We demonstrate that compared to IFNλ3, wild-type human IFNλ4 induces a signalling response with distinct magnitudes and kinetics, which is modified by naturally-occurring variants P70S and K154E in both cell types. IFNλ4’s distinct antiviral response was more rapid yet transient compared to IFNλ1 and 3. Additionally, divergent antiviral kinetics were also observed using non-human primate IFNλs and cell lines. Furthermore, an IFNλ4-like receptor-interacting interface failed to alter IFNλ1’s kinetics. Together our data provide further evidence that major functional differences exist within the IFNλ gene family. These results highlight the possible tissue specialisation of IFNλs and encourage further investigation of the divergent, non-redundant activities of IFNλ4 and other IFNλs.

Contribution to the Field

Viral infections remain major causes of death and disease in humans and other animals. Interferons (IFNs) are a diverse group of host signalling proteins that can induce a potent antiviral state in cells and are intimately involved in the outcome of infection. Genetic variants within one IFN (interferon lambda 4, IFNλ4) are associated with the outcome of hepatitis C infection in humans. However, how IFNλ4 functions – and how natural variants affect its activity - remains poorly understood. Comparing how the antiviral activity changes over time following stimulation with different IFNλs, we identified that IFNλ4 induces a more rapid antiviral state compared to other IFNλs in liver and intestinal cells. Importantly, this response was conserved within human variants and between humans and non-human primates (chimpanzee and Rhesus macaque). Our results shed light on the unique functions of the divergent IFNλ4 protein.
Interpretable deep generative models for genomics
Authors: Choi Yongin , Li Ruoxin , Quon Gerald
Published: September 2021

Deep neural networks implementing generative models for dimensionality reduction have been extensively used for the visualization and analysis of genomic data. One of their key limitations is lack of interpretability: it is challenging to quantitatively identify which input features are used to construct the embedding dimensions, thus preventing insight into why cells are organized in a particular data visualization, for example. Here we present a scalable, interpretable variational autoencoder (siVAE) that is interpretable by design: it learns feature embeddings that guide the interpretation of the cell embeddings in a manner analogous to factor loadings of factor analysis. siVAE is as powerful and nearly as fast to train as the standard VAE but achieves full interpretability of the embedding dimensions. Using siVAE, we exploit a number of connections between dimensionality reduction and gene network inference to identify gene neighborhoods and gene hubs, without the explicit need for gene network inference. We observe a systematic difference in the gene neighborhoods identified by dimensionality reduction methods and gene network inference algorithms in general, suggesting they provide complementary information about the underlying structure of the gene co-expression network. Finally, we apply siVAE to implicitly learn gene networks for individual iPSC lines and uncover a correlation between neuronal differentiation efficiency and loss of co-expression of several mitochondrial complexes, including NADH dehydrogenase, cytochrome C oxidase, and cytochrome b.
Acidity and sulfur oxidation intermediate concentrations controlled by O2-driven partitioning of sulfur oxidizing bacteria in a mine tailings impoundment
Authors: Whaley-Martin Kelly J. , Chen Lin-Xing , Nelson Tara Colenbrander , Gordon Jennifer , Kantor Rose , Twible Lauren E. , Marshall Stephanie , Rossi Laura , Bessette Benoit , Baron Christian , Apte Simon , Banfield Jillian F. , Warren Lesley A.
Published: September 2021

Acidification of freshwater in mining impacted areas is a major global environmental problem catalyzed by sulfur-oxidizing bacteria (SOB). To date, little is known about the active bacteria in mine tailings impoundments and their environmental niches. Here, biological sulfur oxidation was investigated over four years in a mine tailings impoundment, integrating sulfur geochemistry, genome-resolved metagenomics and metatranscriptomics. We demonstrated oxygen driven niche partitioning of SOB and their metabolic pathways that explain acidity generation and thiosulfate persistence. Four chemolithoautotrophic SOB, Halothiobacillus, Thiobacillus, Sulfuricurvum and Sediminibacterium comprised 37% to 73% of the analyzed communities. The impoundment waters alternated between the dominance of Halothiobacillus versus a Thiobacillus, Halothiobacillus, Sulfuricurvum and Sediminibacterium consortia. Halothiobacillus dominance was associated with lower pH values (∼4.3), higher [H+]/[SO42-] and lower [S2O32-], collectively indicative of extensive sulfur oxidation. Halothiobacillus, which couple sulfur oxidation via the Sox pathway to aerobic respiration or NO2- reduction, were present throughout the depth profile, yet their expression of sox genes occurred only in upper highly oxygenated waters. Conversely, when consortia of Thiobacillus, Halothiobacillus, Sulfuricurvum and Sediminibacterium dominated, recycling/disproportionating reactions were more prevalent. Thiobacillus, which dominated deeper micro-oxic/anoxic waters, oxidized sulfur primarily through the rDSR pathway, coupled to NO3-/NO2- reduction, resulting in lower [H+]/[SO42-] and higher [S2O32-] relative to upper waters. These field results mirror the Sox/rDSR-geochemical patterns of experimental SOB enrichments and reveal opportunities for biological treatments of recalcitrant reduced sulfur compounds, as well as gene-based monitoring and in situ RNA detection to predict the onset of problematic geochemistry.
Photoinduced Isomerization Sampling of Retinal in Bacteriorhodopsin
Authors: Ren Zhong
Published: September 2021

Photoisomerization of retinoids inside a confined protein pocket represents a critical chemical event in many important biological processes from animal vision, non-visual light effects, to bacterial light sensing and harvesting. Light driven proton pumping in bacteriorhodopsin entails exquisite electronic and conformational reconfigurations during its photocycle. However, it has been a major challenge to delineate transient molecular events preceding and following the photoisomerization of the retinal from noisy electron density maps when varying populations of intermediates coexist and evolve as a function of time. Here I report several distinct early photoproducts deconvoluted from the recently observed mixtures in time-resolved serial crystallography. This deconvolution substantially improves the quality of the electron density maps hence demonstrates that the all-trans retinal undergoes extensive isomerization sampling before it proceeds to the productive 13-cis configuration. Upon light absorption, the chromophore attempts to perform trans-to-cis isomerization at every double bond together with the stalled anti-to-syn rotations at multiple single bonds along its polyene chain. Such isomerization sampling pushes all seven transmembrane helices to bend outward, resulting in a transient expansion of the retinal binding pocket, and later, a contraction due to recoiling. These ultrafast responses observed at the atomic resolution support that the productive photoreaction in bacteriorhodopsin is initiated by light-induced charge separation in the prosthetic chromophore yet governed by stereoselectivity of its protein pocket. The method of a numerical resolution of concurrent events from mixed observations is also generally applicable.

Significance Statement

Photoisomerization of retinal is a critical rearrangement reaction in many important biological processes from animal vision, non-visual light effects, to bacterial light sensing and harvesting. It has been a major challenge to visualize rapid molecular events preceding and following photoisomerization so that many protein functions depending on such reaction remain vaguely understood. Here I report a direct observation of the stereoselectivity of bacteriorhodopsin hence delineate the structural mechanism of isomerization. Upon a light-induced charge separation, the retinal in a flat conformation attempts to perform double bond isomerization and single bond rotation everywhere along its polyene chain before it proceeds to the specific, productive configuration. This observation improves our understanding on how a non-specific attraction force could drive a specific isomerization.
The landscape of nucleotide diversity inDrosophila melanogasteris shaped by mutation rate variation
Authors: Barroso Gustavo V. , Dutheil Julien Y.
Published: September 2021

What shapes the distribution of nucleotide diversity along the genome? Attempts to answer this question have sparked debate about the roles of neutral stochastic processes and natural selection in molecular evolution. However, the mechanisms of evolution do not act in isolation, and integrative models that simultaneously consider the influence of multiple factors on diversity are lacking; without them, confounding factors lurk in the estimates. Here we present a new statistical method that jointly infers the genomic landscapes of genealogies, recombination rates and mutation rates. In doing so, our model captures the effects of genetic drift, linked selection and local mutation rates on patterns of genomic variation. We then formalize a causal model of how these microevolutionary mechanisms interact, and cast it as a linear regression to estimate their individual contributions to levels of diversity along the genome. Our analyses reclaim the well-established signature of linked selection inDrosophila melanogaster,but we estimate that the mutation landscape is the major driver of the genome-wide distribution of diversity in this species. Furthermore, our simulation results suggest that in many evolutionary scenarios the mutation landscape will be a crucial factor shaping diversity, depending notably on the genomic window size. We argue that incorporating mutation rate variation into the null model of molecular evolution will lead to more realistic inferences in population genomics.
CRISPR-Cas Inhibits Natural Transformation Through Altruistic Group Defense and Self-Sacrifice
Authors: Cooper Robert M. , Hasty Jeff
Published: September 2021

CRISPR-Cas systems present an evolutionary tradeoff: does defense against phages and other parasitic DNA also prevent cells from acquiring potentially helpful new genes? Genomic analyses of this conundrum have arrived at often contradictory conclusions. Meanwhile, experimental studies have focused mainly on phages, conjugation, or artificial transformation, but less work has examined natural competence, a major driver of evolution and antibiotic resistance. Here, we use Acinetobacter baylyi, which combines high natural competence with a functional CRISPR-Cas system, to experimentally probe the interactions between CRISPR-Cas and natural competence. In these bacteria, the endogenous CRISPR array largely allows natural transformation by targeted DNA. However, CRISPR-Cas then kills the newly autoimmune cells in a form of programmed cell death. CRISPR-Cas often allows self-targeting cells to form colonies, albeit with fitness costs. Thus CRISPR-Cas appears to block natural transformation in a process more akin to altruistic group defense than an individual immune system.
Kinetics of the inflammatory response during experimentalBabesia rossiinfection of beagle dogs
Authors: Atkinson B.K. , Thompson P. , Van Zyl E. , Goddard A. , Rautenbach Y. , Schoeman J.P. , Mukorera V. , Leisewitz A.
Published: September 2021

Babesia rossicauses severe morbidity and mortality in dogs in sub-Saharan Africa, and the complications associated with this disease are likely caused by an unfocused, excessive inflammatory response. During this experimentalB. rossistudy we investigated inflammatory marker and cytokine kinetics during infection and after treatment. We aimed to determine whether infectious dose and treatment would influence the progression of the inflammatory response and clinical disease. Five healthy male beagle dogs were infected withB. rossi, three with a high infectious dose (HD group) and two with a low infectious dose (LD group). Clinical examination, complete blood count (CBC) and C-reactive protein (CRP) were determined daily. Cytokines were quantified on stored plasma collected during the study, using a canine specific cytokine magnetic bead panel (Milliplex©). The experiment was terminated when predetermined endpoints were reached. Parasitemia occurred on day 1 and 3 in the HD group and LD group respectively. The rate of increase in parasitemia in the HD group was significantly faster than that seen in the LD group. Significant differences were found in heart rate, blood pressure, interferon gamma (INFγ), keratinocyte chemoattractant (KC), INFγ-induced protein 10 (IP10), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP1), tumor necrosis factor alpha (TNFα), interleukin 2 (IL-2), IL-6, IL-7, IL-8, IL-10 IL-15, IL-18, CRP, neutrophils and monocytes between groups at multiple time points during the course of the infection. Our findings suggest that the initiation of inflammation occurs before the onset of clinical disease inB. rossiinfection and infectious dose influences the onset of the inflammatory response. Treatment not only fails to curb the inflammatory response but may enhance it. Finally, we found that there is an imbalance in pro/anti-inflammatory cytokine concentrations during infection which may promote parasite replication.
Cytokine gene polymorphism and parasite susceptibility in free-living rodents: importance of non-coding variants
Authors: Kloch Agnieszka , Mierzejewska Ewa J , Welc-Falęciak Renata , Bajer Anna , Biedrzycka Aleksandra
Published: September 2021

Associations between genetic variants and susceptibility to infections have long been studied in free-living hosts to infer contemporary evolutionary forces shaping genetic polymorphisms of the immunity genes. Despite extensive studies of receptors, such as MHC or TLR, little is known about efferent arm of the immune system. Cytokines are signalling molecules that trigger and modulate the immune response, acting as a crucial link between innate and adaptive immunity. In the present study we investigated how genetic variation in cytokines affects susceptibility to parasitic diseases in bank voles. We focused on three cytokines: tumour necrosis factor (TNF), lymphotoxin alpha (LTα), and interferon beta (IFNβ1). Two SNPs in LTα and two in IFNβ1 significantly affected susceptibility to nematodes, and was of them was also associated with susceptibility to microbial pathogen Bartonella. All these variants displayed signatures of selection. One of the variants was synonymous, and one was located in an intron. Our study shows that cytokines are prone to parasite-driven selection, and non-coding variants may play an important role in susceptibility to infections in wild systems.
The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis
Authors: Roblek Marko , Bicher Julia , van Gogh Merel , György Attila , Seeböck Rita , Szulc Bozena , Damme Markus , Olczak Mariusz , Borsig Lubor , Siekhaus Daria
Published: September 2021

Solute carriers are increasingly recognized as participating in a plethora of pathologies, including cancer. We describe here the involvement of the orphan solute carrier MFSD1 in the regulation of tumor cell migration. Loss of MFSD1 enabled higher levels of metastasis in a mouse model. We identified an increased migratory potential in MFSD1-/-tumor cells which was mediated by increased focal adhesion turn-over, reduced stability of mature inactive β1 integrin, and the resulting increased integrin activation index. We show that MFSD1 promoted recycling to the cell surface of endocytosed inactive β1 integrin and thereby protected β1 integrin from proteolytic degradation; this led to dampening of the integrin activation index. Furthermore, down-regulation of MFSD1 expression was observed during early steps of tumorigenesis and higher MFSD1 expression levels correlate with a better cancer patient prognosis. In sum, we describe a requirement for endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor spread.
Ethyl 2-[(E)-({2,4-dimethoxy-6-[2-(4-methoxyphenyl)ethenyl]benzylidene}amino)oxy]acetate
Authors: Sung Jiha
Published: September 2021

In the title compound, C22H25NO6, the C=C double bond linking the benzene rings adopts an E configuration and the dihedral angle between the rings is 47.1 (2)°. The oxime unit contains a C=N double bond, which also has an E configuration. In the crystal, pairs of C—H...N hydrogen bonds generate inversion dimers and weak C—H...O interactions link the dimers into chains propagating along the b-axis direction.
Change in brand attitude depending on fashion film type: the psychological mechanisms by engagement and consumer fantasy proneness
Authors: Park Hyun Hee
Published: September 2021

Purpose

This study investigates the effect of consumers' brand attitude changes according to the fashion film type. Furthermore, it examines the psychological mechanism by engagement and consumer fantasy proneness. This study is meaningful because it provides a more in-depth understanding of the use of fashion film as a means of consumer-oriented persuasion communication.

Design/methodology/approach

This research uses a 2(fashion film type: narrative vs non-narrative) × 2(consumer fantasy proneness: high vs low) mixed factorial design to test the hypotheses. ANOVA and the PROCESS macro mounted on SPSS was used to test hypotheses.

Findings

The group with high consumer fantasy proneness showed more changes in brand attitude when exposed to non-narrative than narrative fashion films, but the group with low consumer fantasy proneness showed no significant difference in brand attitude change according to the fashion film type. In addition, when consumer fantasy proneness is high, media and brand engagement for non-narrative fashion films increase sequentially, resulting in a greater change in brand attitude, whereas these psychological mechanisms do not work in groups with low consumer fantasy proneness.

Practical implications

Fashion brands should identify their respective target group when producing fashion films and choose differentiated narrative forms. In the case of pursuing a fantastic aesthetic value, the non-narrative type induces more attention and curiosity from consumers than the narrative type, which affects the feeling of a special bond or relevance with the brand.

Originality/value

This study has value in that it demonstrates the rationale for why a fashion brand needs to select a differentiated content structure according to the aesthetic value pursued when making a fashion film in branding work.
Consumer adoption of online-to-offline food delivery services in China and New Zealand
Authors: Wang Ou , Scrimgeour Frank
Published: September 2021

Purpose

This study explores impacts of innovation-adoption characteristics, food choice motives, segmentation and socio-demographics on consumer adoption of online-to-offline food delivery services (O2O-FDS) in a Western developed country – New Zealand – and an Asian developing country – China.

Design/methodology/approach

An online survey of 1,185 consumers provides data that the authors analyse using factor analyses, structural equation modelling and cluster analysis.

Findings

The following innovation-adoption characteristics and food choice motives have statistically significant effects on consumers' attitudes and/or purchase intentions towards O2O-FDS in the pooled sample and/or the samples of two countries: perceived incentive, perceived complexity, processed convenience, cheapness, taste appeal, safety-assured and purchase convenience. Three consumer segments are recognized: conservatives (26.6%), food-value seekers (40.8%) and pioneers (32.6%). Significant differences are found in marital status, age, household income, education level, household size, occupation, country and residential areas across the three segments.

Originality/value

This is the first study to systematically understand significant influencing factors for the O2O-FDS adoption by using a sample set composed of both Eastern and Western consumers.
A qualitative conceptual framework to tackle skill shortages in offsite construction industry: a scientometric approach
Authors: Saad Syed , Alaloul Wesam Salah , Ammad Syed , Qureshi Abdul Hannan
Published: September 2021

Purpose

This study assessed the key construction technology trends and tracked the impact of these developments on labor influencing factors in an effort to alleviate the limitations posed by skilled labor scarcity in offsite construction (OSC).

Design/methodology/approach

The study followed systematic literature review to acquisition initial data sets. The data retrieved form identified databases was then subjected to scientometric analysis. In next stage, disruptive factors were identified to produce a conceptual framework followed by its practical application for an OSC firm.

Findings

This study identified seven construction technologies with a potential to disrupt OSC in future. The study also developed a conceptual framework as a benchmark to help establish further frameworks for policy interns in OSC.

Research limitations/implications

The review conducted only takes into account the literature from 2009 to March 2021. Any prior to the date and unpublished studies were not included in study.

Practical implications

A proper utilization of conceptual framework can contribute to technological adoption significantly lowering the need of labor in OSC industry. Moreover, the established discussion on understanding the purpose of deploying latest technology may reduce additional costs, management, time and allocation of labor resources.

Social implications

This study provides a mechanism to intern OSC policymakers to impartially incorporate the latest technology in OSC.

Originality/value

This study fulfilled an identified need to study latest technological trends in OSC by utilizing bibliometric tools with SLR. The disruptive categories and factors highlighted by the study were not identified in a systematic manner in previous studies, which could further enhance the implementation of latest construction technology in OSC.
My future entrepreneurial self: antecedents of entrepreneurial identity aspiration
Authors: Gregori Patrick , Holzmann Patrick , Schwarz Erich J.
Published: September 2021

Purpose

Entrepreneurial identity aspiration refers to the desire to occupy an entrepreneurial role in the future and is an essential impetus for initially engaging in entrepreneurial activities. Building on identity theory, the article investigates the effects of personal attitudes, experiences and inclination towards specific practices on the strength of entrepreneurial identity aspiration.

Design/methodology/approach

This article applies multiple linear regression analysis to test the developed hypotheses on an original sample of 127 vocational college students in Austria.

Findings

Results show that risk-taking propensity, proactiveness, entrepreneurial self-efficacy and competitiveness drive entrepreneurial identity aspiration. The effects of innovativeness and need for achievement motivation are nonsignificant. Data further suggest that entrepreneurial identity aspiration is related to gender, while entrepreneurial exposure and previous entrepreneurship education show no or adverse effects.

Practical implications

Based on our findings, the authors argue that education should focus on teaching and discussing the identified attitudes and inclinations to foster the formation of entrepreneurial identities. Doing so increases students' aspirations and provides them with the necessary cognitive underpinnings for subsequent entrepreneurial action. The article suggests action-based teaching to achieve this goal.

Originality/value

This article is the first to investigate antecedents of entrepreneurial identity aspiration by connecting it to essential concepts of entrepreneurship research. The authors extend previous work on entrepreneurial identity and add to the theoretical approaches for research in entrepreneurship education. Furthermore, the article points out central aspects that should receive additional attention in educational settings.
Theorizing artificial intelligence acceptance and digital entrepreneurship model
Authors: Upadhyay Nitin , Upadhyay Shalini , Dwivedi Yogesh K.
Published: September 2021

Purpose

This paper aims to determine the entrepreneur's intention to accept artificial intelligence (AI) and provide advancement in the domain of digital entrepreneurship.

Design/methodology/approach

Extensive literature review and theories have been considered in the area of technology adoption/acceptance and digital entrepreneurship to identify the factors affecting the intention of entrepreneurs with respect to accept AI for digital entrepreneurship. Further, a model, artificial intelligence acceptance and digital entrepreneurship (AIADE) is theorized after formulating some hypotheses. The theorized model has been validated with 476 useable responses.

Findings

The findings revealed that performance expectancy, openness, social influence, hedonic motivations and generativity have a positive impact on entrepreneur's acceptance intention of AI. Additionally, affordance has no direct relationship with AI acceptance intention, but it affects AI acceptance intention through attitude. Inconvenience has a significant negative relationship with the intention to accept AI, while uncertainty was found to be positively affecting the AI acceptance intention. Effort expectancy did not confirm any significant relationship.

Research limitations/implications

By considering existing theoretical models and concepts the authors contribute to the AI's theoretical progress, specifically in the domain of entrepreneurship. The authors complement and extend existing technology adoption/acceptance theories and digital entrepreneurship theories by developing a theoretical model, AIADE, explaining the entrepreneur's intention to accept AI.

Practical implications

The practical implications of the study show that performance expectancy (positive), openness (positive), social influence (positive), hedonic motivations (positive), generativity (positive), affordance through attitude (positive), uncertainty (positive), effort expectancy (negative) and inconvenience (negative) are the antecedents for the entrepreneurs to accept AI for digital entrepreneurship. The authors suggest that intentional improvement planning is developed by increasing entrepreneur's positive perceptions of AI affordance and explanation of its generativity and openness, and improving their attitude of using AI for digital entrepreneurship.

Originality/value

This is the first study that reveals the critical antecedents of entrepreneur's intention to accept AI for digital entrepreneurship. Relevant theoretical background, discussion, implications, limitations and future research recommendations are discussed.
Cash waqf from the millennials' perspective: a case of Indonesia
Authors: Nour Aldeen Khaled , Ratih Inayah Swasti , Sari Pertiwi Risa
Published: September 2021

Purpose

The purpose of this study is to explore the awareness and willingness level of millennials in Indonesia towards cash waqf (cash endowment). Cash waqf has gained huge attention in Indonesia because of its flexibility, especially after the Majlis Ulama Indonesia (MUI) officially announcing in 2002 that cash waqf practices in the country are Sharīʿah-compliant. Millennials comprise 33.75% of the total Indonesian population. Therefore, it is vital to analyze cash waqf from an Indonesian perspective. This study provides vital information for all institutions that are concerned with the enhancement of cash waqf contributions in Indonesia.

Design/methodology/approach

Self-structured questionnaires were distributed in Java Island to collect the data. The data were examined by employing suitable statistical tools. Besides, post-interview fact-finding was conducted with cash waqf experts from different related institutions in Indonesia to reach a more in-depth understanding about cash waqf issues.

Findings

The results depict a high level of awareness about cash waqf among millennials in Indonesia. The results further reveal a lower willingness level to contribute to cash waqf of the sample population as compared to their level of awareness about cash waqf. Moreover, cash waqf promotions must focus on delivering a deeper understanding about the concept and how it differs from other types of Islamic philanthropy. The results suggest that waqf trustees in the country must be more transparent. Moreover, the Indonesian Waqf Board should implement stricter rules to monitor waqf trustees.

Research limitations/implications

This research restricts the sample population to Indonesian Muslims who were born between 1980 and 2000.

Practical implications

As a Muslim-majority country, one would expect Indonesia to make much progress in cash waqf. By providing an explanatory understanding of willingness and awareness of cash waqf among Indonesians, this research can be helpful in designing proper educative marketing campaigns for future endowers to cash waqf activities to ensure cash waqf institutions provide efficient services. It is advisable to emphasize the transparency of waqf organizations. This will add to the nāz˙irs’ (waqf trustee) reputation, thereby boosting waqf's national shares by ensuring a proper allocation of cash waqf. The regulator should be more strict in monitoring nāz˙ir practices. For instance, it could include a periodic assessment of waqf entities.

Originality/value

This study is original in nature; there is no previous study that addresses the millennial’s perspective toward cash waqf in Indonesia. Hence, this study presents precious information for policy makers, practitioners and researchers.
Detecting the historical roots of education for sustainable development (ESD): a bibliometric analysis
Authors: Zhang YuYing , Wang Peng
Published: September 2021

Purpose

Although several researchers have statistically analyzed references associated with education for sustainable development based on the co-citation frequency, evolutionary analysis based on high-citation references omits literature with low citation frequency, which has a significant impact on the evolution of a discipline. The purpose of this study is to understand and explore the historical processes and roots of the field of education for sustainable development and to understand the theoretical grounding of the field.

Design/methodology/approach

Based on education for sustainable development publications in the science citation index expanded and social sciences citation index databases from 1992 to August 2020, a new bibliometric method, reference publication year spectroscopy, was adopted to conduct a bibliometric analysis of the 58,588 cited references in 1,778 publications.

Findings

The earliest reference in the field of education for sustainable development traces back to 1732. There were 21 peaks in this field between 1732 and August 2020. Dewey’s “new three-center theory”; Bloom’s “taxonomy”; Freire’s “conscientization theory”; the “theory of planned behavior”; Kolb’s “experiential learning theory”; Wittgenstein’s theoretical concepts of “language-games,” “forms of life” and “rule-following” and Leopold’s “land ethics” laid an early theoretical grounding of educational philosophy and environmental ethics for research into education for sustainable development. The new environmental paradigm and the new ecological paradigm have become the most widely used methodological tools for understanding the values and attitudes of people toward the natural environment. Among the 50 most cited references, Lozano and Wals have published the most publications, contributing to promoting the development of research into education for sustainable development. The Journal of Cleaner Production, International Journal of Sustainability in Higher Education and Environmental Education Research have published the most publications related to the field of education for sustainable development.

Originality/value

The findings of this study are helpful for scholars and practitioners to understand the academic ideological roots, theoretical grounding and important influential literature in the field of education for sustainable development.