bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational study on Strontium ion modified Fibronectin-Hydroxyapatite interaction
Authors: Basu Subhadip , Basu Bikramjit , Maiti Prabal K
Published: September 2021

Protein adsorption is the first key step in cell-material interaction. The initial phase of such adsorption process can only be probed using modelling approaches like molecular dynamics (MD) simulation. Despite a large number of studies on the adsorption behaviour of proteins on different biomaterials including hydroxyapatite (HA); little attention has been paid towards quantitative assessment of the effects of various physicochemical influencers like surface modification, pH, and ionic strength. Among these factors, surface modification through isomorphic substitution of foreign ions inside the apatite structure is of particular interest in the context of protein-HA interaction as it is widely used to tailor the biological response of HA. Given this background, we present here the molecular-level understanding of fibronectin (FN) adsorption mechanism and kinetics on Sr2+-doped HA (001) surface, at 300K by means of all-atom molecular dynamics simulation. Electrostatic interaction involved in adsorption of FN on HA was found to be significantly modified in presence of Sr2+ doping in apatite lattice. In harmony with the published experimental observations, the Sr-doped surface was found to better support FN adhesion compared to pure HA, with 10 mol% Sr-doped HA exhibiting best FN adsorption. Sr2+ ions also influence the stability of the secondary structure of FN, as observed from the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analysis. The presence of Sr2+ enhances the flexibility of specific residues (residue no. 20-44, 74-88) of the FN module. Rupture forces to disentangle FN from the biomaterials surface, obtained from steered molecular dynamics (SMD) simulations, were found to corroborate well with the results of equilibrium MD simulations. One particular observation is that, the availability of RGD motif for the interaction with cell surface receptor integrin is not significantly influenced by Sr2+ substitution. Summarizing, the present work establishes a quantitative foundation towards the molecular basis of the earlier experimentally validated better cytocompatibility of Sr-doped HA.
Structures of plasmepsin X from P. falciparum reveal a novel inactivation mechanism of the zymogen and molecular basis for binding of inhibitors in mature enzyme
Authors: Kesari Pooja , Deshmukh Anuradha , Pahelkar Nikhil , Suryawanshi Abhishek B. , Rathore Ishan , Mishra Vandana , Dupuis John H. , Xiao Huogen , Gustchina Alla , Abendroth Jan , Labaied Mehdi , Yada Rickey Y. , Wlodawer Alexander , Edwards Thomas E. , Lorimer Donald D. , Bhaumik Prasenjit
Published: September 2021

Plasmodium falciparum plasmepsin X (PfPMX), involved in the invasion and egress of this deadliest malarial parasite, is essential for its survival and hence considered as an important drug target. We report the first crystal structure of PfPMX zymogen containing a novel fold of its prosegment. A unique twisted loop from the prosegment and arginine 244 from the mature enzyme are involved in zymogen inactivation; such mechanism, not previously reported, might be common for apicomplexan proteases similar to PfPMX. The maturation of PfPMX zymogen occurs through cleavage of its prosegment at multiple sites. Our data provide thorough insights into the mode of binding of a substrate and a potent inhibitor 49c to PfPMX. We present molecular details of inactivation, maturation, and inhibition of PfPMX that should aid in the development of potent inhibitors against pepsin-like aspartic proteases from apicomplexan parasites.
Knowledge-driven perceptual organization reshapes information sampling via eye movements
Authors: Pedziwiatr Marek A. , von dem Hagen Elisabeth , Teufel Christoph
Published: September 2021

Humans constantly move their eyes to explore the environment and obtain information. Competing theories of gaze guidance consider the factors driving eye movements within a dichotomy between low-level visual features and high-level object representations. However, recent developments in object perception indicate a complex and intricate relationship between features and objects. Specifically, image-independent object-knowledge can generate objecthood by dynamically reconfiguring how feature space is carved up by the visual system. Here, we adopt this emerging perspective of object perception, moving away from the simplifying dichotomy between features and objects in explanations of gaze guidance. We recorded eye movements in response to stimuli that appear as meaningless patches on initial viewing but are experienced as coherent objects once relevant object-knowledge has been acquired. We demonstrate that gaze guidance differs substantially depending on whether observers experienced the same stimuli as meaningless patches or organized them into object representations. In particular, fixations on identical images became object-centred, less dispersed, and more consistent across observers once exposed to relevant prior object-knowledge. Observers’ gaze behaviour also indicated a shift from exploratory information-sampling to a strategy of extracting information mainly from selected, object-related image areas. These effects were evident from the first fixations on the image. Importantly, however, eye-movements were not fully determined by object representations but were best explained by a simple model that integrates image-computable features and high-level, knowledge-dependent object representations. Overall, the results show how information sampling via eye-movements in humans is guided by a dynamic interaction between image-computable features and knowledge-driven perceptual organization.
Solvent Precipitation SP3 (SP4) enhances recovery for proteomics sample preparation without magnetic beads
Authors: Johnston Harvey E. , Yadav Kranthikumar , Kirkpatrick Joanna M. , Biggs George S. , Oxley David , Kramer Holger B. , Samant Rahul S.
Published: September 2021

Complete, reproducible extraction of protein material is essential for comprehensive and unbiased proteome analyses. A current gold standard is single-pot, solid-phase-enhanced sample preparation (SP3), in which organic solvent and magnetic beads are used to denature and capture proteins, with subsequently washes allowing contaminant removal. However, SP3 is dependent on effective protein immobilisation onto beads, risks losses during wash steps, and experiences a drop-off in protein recovery at higher protein inputs. Magnetic beads may also contaminate samples and instruments, and become costly for larger scale protein preparations. Here, we propose solvent precipitation SP3 (SP4) as an alternative to SP3, omitting magnetic beads and employing brief centrifugation—either with or without low-cost inert glass beads—as the means of aggregated protein capture. SP4 recovered equivalent or greater protein yields for 1–5000 µg preparations and improved reproducibility (median protein R2 0.99 (SP4) vs. 0.97 (SP3)). Deep proteome profiling (n = 9,076) also demonstrated improved recovery by SP4 and a significant enrichment of membrane and low-solubility proteins vs. SP3. The effectiveness of SP4 was verified in three other labs, each confirming equivalent or improved proteome characterisation over SP3. This work suggests that protein precipitation is the primary mechanism of SP3, and reliance on magnetic beads presents protein losses, especially at higher concentrations and amongst hydrophobic proteins. SP4 represents an efficient and effective alternative to SP3, provides the option to omit beads entirely, and offers virtually unlimited scalability of input and volume—all whilst retaining the speed and universality of SP3.

BRIEF

Solvent precipitation SP3 (SP4) captures aggregated protein for proteomics sample clean-up by omitting magnetic beads, instead employing brief centrifugation—with or without low-cost inert glass beads. SP4 offers improvements to protein yields, higher reproducibility, and greater recovery of membrane proteins, with verifications from three labs. Protein precipitation appears to be the primary mechanism of SP3, with reliance on magnetic beads presenting protein losses, especially at higher concentrations. SP4 presents an effective alternative to SP3 with improved scalability and equal speed and universality.

GRAPHICAL ABSTRACT
A method to enrich and purify centromeric DNA from human cells
Authors: Gamba Riccardo , Mazzucco Giulia , Wilhelm Therese , Chardon Florian , Velikovsky Leonid , Picotto Julien , Doksani Ylli , Fachinetti Daniele
Published: September 2021

Centromeres are key elements for chromosome segregation. Canonical centromeres are built over long-stretches of tandem repetitive arrays. Despite being quite abundant compared to other loci, centromere sequences overall still represent only 2 to 5% of the human genome, therefore studying their genetic and epigenetic features is a major challenge. Furthermore, sequencing of centromeric regions requires high coverage to fully analyze length and sequence variations, which can be extremely costly. To bypass these issues, we have developed a technique based on selective restriction digestion and size fractionation to enrich for centromeric DNA from human cells. Combining enzymes capable of cutting at high frequency throughout the genome, except within most human centromeres, with size-selection of >20 kb fragments resulted in over 25-fold enrichment in centromeric DNA. Sequencing of the enriched fractions revealed that up to 60% of the enriched material is made of centromeric DNA. This approach has great potential for making sequencing of centromeric DNA more affordable and efficient and for single DNA molecule studies.
Self-Administration of entactogen psychostimulants dysregulates GABA and Kappa Opioid Receptor signaling in the central nucleus of the amygdala of female Wistar rats
Authors: Khom Sophia , Nguyen Jacques D. , Vandewater Sophia A. , Grant Yanabel , Roberto Marisa , Taffe Michael A.
Published: September 2021

Male rats escalate intravenous self-administration of entactogen psychostimulants, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxymethamphetamine (MDMA) under extended access conditions, as with typical psychostimulants. Here, we investigated whether female rats escalate self-administration of methylone, 3,4-methylenedioxypentedrone (pentylone), and MDMA and then studied consequences of MDMA and pentylone self-administration on GABAA receptor and kappa opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA), a brain area critically dysregulated by extended access self-administration of alcohol or cocaine. Adult female Wistar rats were trained to self-administer methylone, pentylone, MDMA (0.5 mg/kg/infusion), or saline-vehicle using a fixed-ratio 1 response contingency in 6-hour sessions (long-access: LgA) followed by progressive ratio (PR) dose-response testing. The effects of pentylone-LgA, MDMA-LgA and saline on basal GABAergic transmission (miniature postsynaptic inhibitory currents, mIPSCs) and the modulatory role of KOR at CeA GABAergic synapses were determined in acute brain slices using whole-cell patch-clamp. Methylone-LgA and pentylone-LgA rats similarly escalated their drug intake (both obtained more infusions compared to MDMA-LgA rats) however, pentylone-LgA rats reached higher breakpoints in PR tests. At the cellular level, baseline CeA GABA transmission was markedly elevated in pentylone-LgA and MDMA-LgA rats compared to saline-vehicle. Specifically, pentylone-LgA was associated with increased CeA mIPSC frequency (GABA release) and amplitude (postsynaptic GABAA receptor function), while mIPSC amplitudes (but not frequency) was larger in MDMA-LgA rats compared to saline rats. In addition, pentylone-LgA and MDMA-LgA profoundly disrupted CeA KOR signaling such as both KOR agonism (1mM U50488) and KOR antagonism (200nM nor-binaltorphimine) decreased mIPSC frequency suggesting recruitment of non-canonical KOR signaling pathways. This study confirms escalated self-administration of entactogen psychostimulants under LgA conditions in female rats which is accompanied by increased CeA GABAergic inhibition and altered KOR signaling. Collectively, our study suggests that CeA GABA and KOR mechanisms play a critical role in entactogen self-administration like those observed with escalation of alcohol or cocaine self-administration.
A global meta-analysis reveals higher variation in breeding phenology in urban birds than in their non-urban neighbours
Authors: Capilla-Lasheras Pablo , Thompson Megan J. , Sánchez-Tójar Alfredo , Haddou Yacob , Branston Claire J. , Réale Denis , Charmantier Anne , Dominoni Davide M.
Published: September 2021

Cities pose a major ecological challenge for wildlife worldwide. Phenotypic variation, which can result from underlying genetic variation or plasticity, is an important metric to understand eco-evolutionary responses to environmental change. Recent work suggests that urban populations might have higher levels of phenotypic variation than non-urban counterparts. This prediction, however, has never been tested across species nor over a broad geographical range. Here, we conduct a meta-analysis of the avian literature to compare urbanversusnon-urban means and variation in phenology (i.e., lay date) and reproductive effort (i.e., clutch size, number of fledglings). First, we show that urban populations reproduce earlier and have smaller broods than non-urban conspecifics. Second, we show that urban populations have higher phenotypic variation in laying date than non-urban populations. This result arises from differences between populations within breeding seasons, conceivably due to higher landscape heterogeneity in urban habitats. These findings reveal a novel effect of urbanisation on animal life-histories with potential implications for species adaptation to urban environments (which will require further investigation). Higher variation in phenology in birds subjected to urban disturbance could result from plastic responses to a heterogeneous environment, or from higher genetic variation in phenology, possibly linked to higher evolutionary potential.
Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor
Authors: Gogolou Antigoni , Souilhol Celine , Granata Ilaria , Wymeersch Filip J , Manipur Ichcha , Wind Matthew , Frith Thomas JR , Guarini Maria , Bertero Alessandro , Bock Christoph , Halbritter Florian , Takasato Minoru , Guarracino Mario R , Tsakiridis Anestis
Published: September 2021

The neural crest (NC) is an important multipotent embryonic cell population and its impaired specification leads to various developmental defects, often in an anteroposterior (A-P) axial level-specific manner. The mechanisms underlying the correct A-P regionalisation of human NC cells remain elusive. Recent studies have indicated that trunk NC cells, the presumed precursors of the childhood tumour neuroblastoma, are derived from neuromesodermal-potent progenitors of the postcranial body (NMPs). Here we employ human embryonic stem cell differentiation to define how NMP-derived NC cells acquire a posterior axial identity. We show that TBXT, a pro-mesodermal transcription factor, mediates early posterior NC regionalisation together with WNT signalling effectors. This occurs by TBXT-driven chromatin remodelling via its binding in key enhancers within HOX gene clusters and other posterior regulator-associated loci. In contrast, posteriorisation of NMP-derived spinal cord cells is TBXT/WNT-independent and takes place under the influence of FGF signalling. Our work reveals a previously unknown role of TBXT in influencing posterior NC fate and points to the existence of temporally discrete, cell type-dependent modes of posterior axial identity control.
Targeting of MCL-1 in breast cancer associated fibroblasts reverses their myofibroblastic phenotype and pro-invasive properties
Authors: Bonneaud TL , Nocquet L , Basseville A , Weber H , Campone M , Juin PP , Souazé F
Published: September 2021

Cancer associated fibroblasts (CAF) are a major cellular component of epithelial tumors. In breast cancers in particular these stromal cells have numerous tumorigenic effects in part due to their acquisition of a myofibroblastic phenotype. Breast CAFs (bCAFS) typically express MCL-1. We show here that targeting this regulator of mitochondrial integrity using a specific BH-3 mimetic promotes fragmentation of these organelles without inducing cell death. MCL-1 antagonism in primary bCAFs directly derived from human samples mitigates myofibroblastic features and decreases expression of genes involved in actomyosin organization and contractility, associated with a cytoplasmic retention of the transcriptional regulator, Yes-Associated Protein(YAP). Such treatment decreases bCAFs ability to promote cancer cells invasion in 3D co-culture assays. These effects are counteracted by an inhibitor of the mitochondrial fission protein DRP-1, which interacts with MCL-1 upon BH3 mimetic treatment. Our findings underscore the usefulness of targeting MCL-1 in breast cancer ecosystems, not only to favor death of cancer cells but also to counteract the tumorigenic activation of fibroblasts with which they co-evolve.

The authors declare no conflict of interest.
The ectomycorrhizal basidiomycete Laccaria bicolor releases a GH28 polygalacturonase that plays a key role in symbiosis establishment
Authors: Zhang Feng , Labourel Aurore , Haon Mireille , Kemppainen Minna , Silva Machado Emilie Da , Brouilly Nicolas , Veneault-Fourrey Claire , Kohler Annegret , Rosso Marie-Noëlle , Pardo Alejandro , Henrissat Bernard , Berrin Jean-Guy , Martin Francis
Published: September 2021

In ectomycorrhiza, root penetration and colonization of the intercellular space by symbiotic hyphae is thought to rely on the mechanical force that results from hyphal tip growth, enhanced by the activity of secreted cell-wall-degrading enzymes.

Here, we characterize the biochemical properties of the symbiosis-induced polygalacturonase LbGH28A from the ectomycorrhizal fungus Laccaria bicolor. The transcriptional regulation of LbGH28A was measured by qPCR. The biological relevance of LbGH28A was confirmed by generating RNAi-silenced LbGH28A mutants. We localized the LbGH28A protein by immunofluorescence confocal and immunogold cytochemical microscopy in poplar ectomycorrhizal roots.

qPCR confirmed the induced expression of LbGH28A during ectomycorrhiza formation. L. bicolor RNAi mutants have a lower ability to establish ectomycorrhiza confirming the key role of this enzyme in symbiosis. The purified recombinant LbGH28A has its highest activity towards pectin and polygalacturonic acid. In situ localization of LbGH28A indicates that this endopolygalacturonase is located in both fungal and plant cell walls at the symbiotic hyphal front.

The present findings suggest that the symbiosis-induced pectinase LbGH28A is involved in the Hartig net formation and is an important determinant for successful symbiotic colonization.
Identification of Immunodominant T-lymphocyte Epitope Peptides in HPV 1, 2 and 3 L1 Protein for Novel Cutaneous Wart Vaccine
Authors: Toh Wu Han , Wang Chuang-Wei , Chung Wen-Hung
Published: September 2021

Background

Common warts and flat warts are caused by the human papillomavirus (HPV). Peak incidence of wart infection occurs in schoolchildren aged 12-16, where prevalence can be as high as 20%. Traditional treatments aimed at destruction of wart tissue have low clearance rates and high recurrence rates. Occasional reports have even shown warts becoming malignant and progressing into verrucous carcinoma. Current licensed HPV vaccines largely target higher-risk oncogenic HPV types, but do not provide coverage of low-risk types associated with warts. To date, little attention has been given to the development of effective, anti-viral wart treatments.

Objective

This study aims to identify immunodominant T-lymphocyte epitopes from the L1 major capsid protein of HPV 1, 2 and 3, a foundational step in bioengineering a peptide-based vaccine for warts.

Methods

Cytotoxic T-cell and helper T-cell epitopes were predicted using an array of immunoinformatic tools against a reference panel of frequently observed MHC-I and MHC-II alleles. Predicted peptides were ranked based on IC50and IFN-γ Inducer Scores, respectively, and top performing epitopes were synthesized and subjected toin vitroscreening by IFN-γ enzyme-linked immunosorbent spot assay (ELISpot). Independent trials were conducted using PBMCs of healthy volunteers. Final chosen peptides were fused with flexible GS linkers insilicoto design a novel polypeptide vaccine.

Results

Seven immunodominant peptides screened from 44 predicted peptides were included in the vaccine design, selected to elicit specific immune responses across MHC class I and class II, and across HPV types. Evaluation of the vaccine’s properties suggest that the vaccine is stable, non-allergenic, and provides near complete global population coverage (>99%). Solubility prediction and rare codon analysis indicate that the DNA sequence encoding the vaccine is suitable for high level expression inEscherichia coli.

Conclusions

In sum, this study demonstrates the potential and lays the framework for the development of a peptide-based vaccine against warts.
No evidence for aberrant expression of amyloid β and phosphorylated tau proteins in herpes simplex virus-infected human neurons in vivo
Authors: Tran Diana N. , Bakx Amy T.C.M. , van Dis Vera , Aronica Eleonora , Verdijk Robert M. , Ouwendijk Werner J.D.
Published: September 2021

Increasing evidence implicates the neurotropic herpes simplex virus 1 (HSV-1) in the pathogenesis of Alzheimer’s Disease (AD). However, it is unclear whether previously reported findings in HSV-1 cell culture and animal models can be translated to humans. Here, we analyzed clinical specimens from latently HSV-1 infected individuals and individuals with lytic HSV infection of the brain (herpes simplex encephalitis; HSE). Latent HSV-1 DNA load in trigeminal ganglia was identical between AD patients and controls, and latently HSV-infected neurons did not express amyloid β (Aβ) or hyperphosphorylated tau (pTau). Some HSE patient brains presented with ageing-related intraneuronal Aβ accumulations, neurofibrillary tangles (NFT) or extracellular Aβ plaques, but these were neither restricted to HSV-infected neurons nor brain regions containing virus-infected cells. Analysis of unique brain material from an AD patient with concurrent HSE showed that HSV-infected cells frequently localized close to Aβ plaques and NFT, but did not exacerbate AD-related pathology in relation to HSV infection. HSE-associated neuroinflammation was not associated with specific Aβ or pTau phenotypes. Collectively, the data indicate that neither latent nor lytic HSV infection of human neurons in vivo is directly associated with aberrant Aβ or pTau protein expression.
The genome of an apodid holothuroid (Chiridota heheva) provides insights into its adaptation to deep-sea reducing environment
Authors: Zhang Long , He Jian , Tan Peipei , Gong Zhen , Qian Shiyu , Miao Yuanyuan , Zhang Han-Yu , Chen Qi , Zhong Qiqi , Han Guanzhu , He Jianguo , Wang Muhua
Published: September 2021

Cold seeps and hydrothermal vents are deep-sea reducing environments that are characterized by a lack of oxygen, photosynthesis-derived nutrients and a high concentration of reducing chemicals. Apodida is an order of deep-sea echinoderms lacking tube feet and complex respiratory trees, which are commonly found in holothurians.Chiridota hehevaPawson & Vance, 2004 (Apodida: Chiridotidae) is one of the few echinoderms that resides in deep-sea reducing environments. Unlike most cold seep and hydrothermal vent-dwelling animals,C. hehevadoes not survive by maintaining an epi- or endosymbiotic relationship with chemosynthetic microorganisms. The species acquires nutrients by extracting organic components from sediment detritus and suspended material. Here, we report a high-quality genome ofC. hehevaas a genomic reference for echinoderm adaptation to reducing environments.Chiridota hehevalikely colonized its current habitats in the early Miocene. The expansion of the aerolysin-like protein family inC. hehevacompared with other echinoderms might be involved in the disintegration of microbes during digestion, which in turn facilitates the species’ adaptation to cold seep environments. Moreover, several hypoxia-related genes were subject to positive selection in the genome ofC. heheva, which contributes to their adaptation to hypoxic environments.
Dynamics ofAedes albopictusinvasion Insights from a spatio-temporal model
Authors: Roques L , Boivin T , Papaïx J , Soubeyrand S , Bonnefon O
Published: September 2021

France displays a latitudinal range for the expansion ofAedes albopictusinvasive populations that is not yet completely colonized providing a critical opportunity to address key invasion processes. We propose a spatio-temporal model (DISTIGRI) to describe and predict current and future expansion at both intra- and inter-annual scales ofA. albopictus. This process-based model integrates mechanistic descriptions of the developmental cycle and the dispersal process ofA. albopictuswithin a reaction-diffusion framework, depending on climatic suitability and photoperiod with a high spatio-temporal resolution. Using this model coupled with a climatic database, we propose several maps describing the current intra-annual distribution ofA. albopictus, including the date of first emergence and the length of the period with significant adult presence. We also compute its future distribution over the next 10 years under several climatic scenarios, which shows a range expansion with a strong dependence on the climatic scenario. The outputs of the model may constitute a valuable asset for designing control and avoidance strategies, and to anticipate the biting nuisance with a high spatio-temporal resolution. These outputs also emphasize the importance of taking both dispersal and life cycle into account to obtain accurate descriptions of out-of-equilibrium processes such as ongoing invasions.
Intraspecific de novo gene birth revealed by presence–absence variant genes in Caenorhabditis elegans
Authors: Lee Bo Yun , Kim Jun , Lee Junho
Published: September 2021

Genes embed their evolutionary history in the form of various alleles. Presence–absence variants (PAVs) are extreme cases of such alleles, where a gene present in one haplotype does not exist in another. Since PAVs may result from either birth or death of a gene, PAV genes and their alternative alleles, if available, can represent a basis for rapid intraspecific gene evolution. Here, we traced a possible evolution of PAV genes in the PD1074 and CB4856 C. elegans strains as well as their alternative alleles found in other 14 wild strains, using long-read sequencing technologies. We updated the CB4856 genome by filling 18 gaps and identified 50 novel genes and 7,460 novel isoforms from both strains. We verified 328 PAV genes, out of which 48 were C. elegans-specific. Among these possible newly-born genes, 13 had alternative alleles in other wild strains and, in particular, alternative alleles of three genes showed signatures active transposons. Alternative alleles of four other genes showed another type of signature reflected in accumulation of small insertions or deletions. Our results exemplify that research on gene evolution using both species-specific PAV genes and their alternative alleles is expected to provide new perspectives for how genes evolve.
An open innovation approach to co-produce scientific knowledge: an examination of citizen science in the healthcare ecosystem
Authors: Ciasullo Maria Vincenza , Carli Mariarosaria , Lim Weng Marc , Palumbo Rocco
Published: September 2021

Purpose

The article applies the citizen science phenomenon – i.e. lay people involvement in research endeavours aimed at pushing forward scientific knowledge – to healthcare. Attention is paid to initiatives intended to tackle the COVID-19 pandemic as an illustrative case to exemplify the contribution of citizen science to system-wide innovation in healthcare.

Design/methodology/approach

A mixed methodology consisting of three sequential steps was developed. Firstly, a realist literature review was carried out to contextualize citizen science to healthcare. Then, an account of successfully completed large-scale, online citizen science projects dealing with healthcare and medicine has been conducted in order to obtain preliminary information about distinguishing features of citizen science in healthcare. Thirdly, a broad search of citizen science initiatives targeted to tackling the COVID-19 pandemic has been performed. A comparative case study approach has been undertaken to examine the attributes of such projects and to unravel their peculiarities.

Findings

Citizen science enacts the development of a lively healthcare ecosystem, which takes its nourishment from the voluntary contribution of lay people. Citizen scientists play different roles in accomplishing citizen science initiatives, ranging from data collectors to data analysts. Alongside enabling big data management, citizen science contributes to lay people's education and empowerment, soliciting their active involvement in service co-production and value co-creation.

Practical implications

Citizen science is still underexplored in healthcare. Even though further evidence is needed to emphasize the value of lay people's involvement in scientific research applied to healthcare, citizen science is expected to revolutionize the way innovation is pursued and achieved in the healthcare ecosystem. Engaging lay people in a co-creating partnership with expert scientist can help us to address unprecedented health-related challenges and to shape the future of healthcare. Tailored health policy and management interventions are required to empower lay people and to stimulate their active engagement in value co-creation.

Originality/value

Citizen science relies on the wisdom of the crowd to address major issues faced by healthcare organizations. The article comes up with a state of the art investigation of citizen science in healthcare, shedding light on its attributes and envisioning avenues for further development.
Intangible resources and firms' innovation performance: empirical evidence from Chinese firms
Authors: Fang Xiuyuan , Jiang Marshall S. , Li Yugang
Published: September 2021

Purpose

Intangible resources (IRs) play an important role in enterprise innovation; previous studies find inconsistent results (positive and negative). The authors develop and test a framework to analyze IRs to see whether and how to impact firm innovation performance to reconcile the conflicting results.

Design/methodology/approach

This study empirically examined the curvilinear effect of IRs and innovation performance (IP) based on data from the Annual Census of Chinese Industrial Enterprises. The moderating effect of institutional development (ID) and state ownership (SO) in the relationship between firms' IRs and IP was also examined.

Findings

It was found that there is a U-shaped relationship between IRs and IP. Moreover, the institutional development weakens the U-shaped relationship.

Originality/value

The U-shaped relationship explains the inconsistent results in previous studies. It offers some important implications for managers and policymakers, who must understand the role of IRs.
Modelling oil product prices with due regard to proliferation of alternative fuels and tightening of technical standards
Authors: Ulanov Vladimir , Skorobogatko Oleg
Published: September 2021

Purpose

This paper aims to clarify the relationship between oil product prices and factors describing the most crucial emerging trends in fuel consumption. The work is aimed to test the hypothesis that the proliferation of alternative fuel cars is a significant factor in determining the level of motor fuel prices. The influence of technical standards of oil products on the model parameters is also analysed.

Design/methodology/approach

The hypothesis testing is carried out on the basis of an econometric analysis of information regarding the North-West European commodity market and the data on the registration of alternative fuel passenger vehicles. Time series are analysed for the presence of a structural shift in the parameters of the model as a result of changes in the requirements of technical regulations for fuel.

Findings

The results suggest a different nature of the influence of the proliferation of alternative fuel passenger vehicles – it has little effect on diesel prices, whilst the indicators under study have a negative effect on the prices of motor gasoline. The construction of oil product price models has confirmed the impact of tightening the technical requirements for the parameters of dependence equations.

Practical implications

The obtained results can be used in forecasting price indicators in oil refining for strategic and investment purposes.

Originality/value

This paper fulfils an identified need to take into account the emerging global trends in fuel consumption to obtain reliable parameters for oil product price modelling.
Dendritic prioritization through spatial stream network modeling informs targeted management of Himalayan riverscapes under brown trout invasion
Authors: Sharma Aashna , Dubey Vineet K. , Johnson Jeyaraj A. , Rawal Yogesh K. , Sivakumar Kuppusamy
Published: September 2021

With the concept of ‘riverscapes’ long pending to be acknowledged in the ‘landscape‐centric’ legislative framework of Himalayan nations, conservation of native riverine species stays practically unheeded. This necessitates urgent prioritization of stream networks to conserve the lotic taxa under invasion pressures. Himalayan riverscapes are pervaded with the invasive‐exotic brown trout Salmo trutta, posing serious threats to the co‐occurring native, the snow trout Schizothorax richardsonii.

Using intensive surveys (218.7 km) and geostatistical stream network models (n = 537), we contrasted snow trout in two stream networks with and without invasives, for assessing differences in their spatial distribution.

Our models indicate invasion‐induced relegations of natives from the river mainstem into headwaters, with large sections of mainstem occupied by invasives. Furthermore, a concerningly small percentage of potential habitat left for natives to occupy in the mainstem is threatened, where a 100% overlap of native and invasive trout distributions is predicted.

With a higher presence probability for the natives in headwaters of invaded watershed as compared to the non‐invaded watershed, we highlight the headwater streams as potential refugia for the natives under invasion.

Synthesis and Applications. Our approach of basin‐scale dendritic prioritization provides immediate management solutions to tackle brown trout invasion threats in Himalaya. We inform decisions on delineation of headwaters as invasion refugia for native fish, with assisted recovery of their fragmented populations in the river mainstems through targeted management of invasives.
Mercury poisoning in two patients with tertiary syphilis from the Ca’ Granda hospital (17th‐century Milan)
Authors: Biehler‐Gomez Lucie , Mattia Mirko , Sala Carlotta , Giordano Gaia , Di Candia Domenico , Messina Carmelo , Sconfienza Luca Maria , Franchini Antonia Francesca , Porro Alessandro , Galimberti Paolo Maria , Slavazzi Fabrizio , Cattaneo Cristina
Published: September 2021

Syphilis was a widespread infectious disease in 17th‐century Italy, commonly treated with mercury‐based ointments and fumigations. Few reports exist on the analysis of abnormally high Hg levels in bone as a result of exposure to mercury‐containing anti‐syphilitic medicine. In this research, two crania recovered among the 2.9 million commingled bones resting under the crypt of the former hospital of the poor of Milan were submitted to pathological, radiological and toxicological analysis. The crania showed gummatous lesions characteristic of tertiary syphilis and inductively coupled plasma mass spectrometry (ICP‐MS) analysis revealed over the double values of Hg in bone relative to that of the control sample. Archival documentation confirms the presence and use of mercury‐based treatments in the pharmacy of the hospitals of Milan. Consequently, the individuals probably came into contact with mercury as a treatment for syphilis, confirming its medical use in 17th‐century Milan and strengthening our knowledge of the history of medicine.
Possible opioid‐saving effect of cannabis‐based medicine using individual‐based data from the Norwegian Prescription Database
Authors: Bramness Jørgen G. , Hjellvik Vidar , Stubhaug Audun , Skurtveit Svetlana
Published: September 2021

Some ecological studies have shown that areas with higher use of cannabis may have lower opioid use and fewer opioid‐related problems. Newer studies are questioning this finding. Few individually based studies have been performed. Using data from the Norwegian Prescription Database, this study investigated the individual level effect of prescribed cannabis extract (Sativex®) in prescription opioid users on their opioid use in the following year. Looking at all those filling a prescription for Sativex®, opioid use was only marginally lowered in the follow‐up period. Some Sativex® users, however, filled more prescriptions for Sativex® and were able to reduce their opioid use substantially. Further studies are needed to elucidate more details on these patients, so as to know who can benefit from such cannabis‐based extracts in reducing their opioid use.
Progressive B cell depletion in human MALT1 deficiency
Authors: Sonoda Motoshi , Ishimura Masataka , Eguchi Katsuhide , Yada Yutaro , Lenhartová Nina , Shiraishi Akira , Tanaka Tamami , Sakai Yasunari , Ohga Shouichi
Published: September 2021

Mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1)-deficiency is a rare combined immunodeficiency characterized by recurrent infections, dermatitis and enteropathy. We herein investigate the immunological profiles of our patient and previously reported children with MALT1-deficiency. A mutation analysis was performed by targeted panel sequencing for primary immunodeficiency. Lymphocyte subset, activation and B cell differentiation were analyzed by flow cytometry and t-distributed stochastic neighbor embedding. Pneumocystis pneumonia developed in a 6-month-old Japanese infant with atopic dermatitis, enteritis and growth restriction. This infant showed agammaglobulinemia without lymphopenia. At 8 years of age, the genetic diagnosis of MALT1-deficiency was confirmed on a novel homozygous mutation of c.1102G>T, p.E368X. T cell stimulation tests showed impairments in the production of interleukin-2, phosphorylation of nuclear factor kappa B (NF-κB) p65 and differentiation of B cells. In combination with the literature data, we found that the number of circulatory B cells, but not T cells, were inversely correlated with the age of patients. The hematopoietic cell transplantation (HCT) successfully reconstituted the differentiation of mature B cells and T cells. These data conceptualize that patients with complete MALT1-deficiency show aberrant differentiation and depletion of B cells. The early diagnosis and HCT lead to a cure of the disease phenotype associated with the loss-of-function mutations in human CARD11.
Managing the identity paradox in inter‐organisational collaborations
Authors: Kourti Isidora
Published: September 2021

A persistent contradiction in inter‐organisational collaborations (IOCs) is between individual actors' IOC identity and their other multiple identities, and the subsequent need to maintain a delicate balance between these opposing but mutually dependent identities. Using a paradox lens and individual actors as the unit of analysis, this ethnographic study defines the “identity paradox” often present in IOCs as the interaction between actors' professional, personal, team and organisational identities with an overall IOC identity. The case demonstrates that the identity paradox allows actors to maintain a balance between adhering to IOC, which offers stability, and adjusting to emergent needs, which enables innovative behaviour. The theorisation of the identity paradox reveals that the conditions that trigger each identity tension relate to the IOC tensions of cooperation and competition, rigidity and flexibility, trust and mistrust, and confrontation and dialogue. The findings offer contribution to IOC research and to management practice.
Science‐Based Practice and the Dangers of Overreach: Essential Concepts and Future Directions in Evidence‐Informed Practice
Authors: Greenberg Lyn R. , McNamara Kathleen , Wilkins Sarah
Published: September 2021

What scientific evidence should we consider in providing services to families? This has become a heated debate, potentially impacting both social policy and intervention planning for families. Overreach has been common in this debate and can seriously harm families. While recognizing the valuable information that randomly‐controlled trials may provide, the authors identify situations in which other scientific information may be more reliable, relevant and helpful for the complex families we serve. They discuss the essential elements of evidence‐informed services, the scope of evidence that may be relevant, and the importance of exercising clinically and scientifically informed inference in planning services.
Climate change research and action must look beyond 2100
Authors: Lyon Christopher , Saupe Erin E. , Smith Christopher J. , Hill Daniel J. , Beckerman Andrew P. , Stringer Lindsay C. , Marchant Robert , McKay James , Burke Ariane , O’Higgins Paul , Dunhill Alexander M. , Allen Bethany J. , Riel‐Salvatore Julien , Aze Tracy
Published: September 2021

Anthropogenic activity is changing Earth's climate and ecosystems in ways that are potentially dangerous and disruptive to humans. Greenhouse gas concentrations in the atmosphere continue to rise, ensuring that these changes will be felt for centuries beyond 2100, the current benchmark for projection. Estimating the effects of past, current, and potential future emissions to only 2100 is therefore short‐sighted. Critical problems for food production and climate‐forced human migration are projected to arise well before 2100, raising questions regarding the habitability of some regions of the Earth after the turn of the century. To highlight the need for more distant horizon scanning, we model climate change to 2500 under a suite of emission scenarios and quantify associated projections of crop viability and heat stress. Together, our projections show global climate impacts increase significantly after 2100 without rapid mitigation. As a result, we argue that projections of climate and its effects on human well‐being and associated governance and policy must be framed beyond 2100.
Impact of foreign direct investment on the haze pollution in various cities: Evidence from China
Authors: Huang Dan , Zhong Shihu , Tang Juan , Zhao Jingjing
Published: September 2021

This study employs panel data of 270 Chinese cities at the prefecture level or above from 2004 to 2018 to examine the impact of foreign direct investment (FDI) on urban haze pollution and its mechanism. The heterogeneity in FDI's impact in cities with different size, development level, government regulation level, the opening degree of the market, and government capacity is also investigated. The results show FDI exacerbates haze pollution in Chinese cities. At the mean value of the samples, a 1% rise in FDI would increase PM2.5 by approximately 0.0073%. These results remain consistent after we experiment several robustness checks. Then, analysis of mechanism suggests that FDI impacts PM2.5 via scale effect, composition effect and technological innovation effect. Finally, heterogeneity analysis further demonstrates haze pollution is more sensitive to the change of FDI in cities with low development level, cities with low market openness, and cities with weak government capacity. Further, it is worth stressing that FDI increases haze pollution in small‐, medium‐, and large sized cities, while it reduces haze pollution in mega cities and above. Moreover, the scale effect, composition effect, and technology effect of FDI in different cities are varied. Policy implications of our work are discussed.
Effects of Bacillus velezensis zk1 on the physiology and metabolism of peaches
Authors: Zeng Yaoying , Yu Qian , Cheng Shujun
Published: September 2021

Bacillus velezensis zk1 is the dominant bacterium that causing rot in peaches. However, the mechanisms through that this bacterium causes rot have not been elucidated. Here, we explored the mechanisms of peach decay caused by B. velezensis zk1. The invasion of B. velezensis zk1 in peaches resulted in an increase in glucose and arabinose contents in fruit tissues. Moreover, the relative conductivity of the fruit reached 84% after 4 days of culture with bacterial invasion. With the destruction of cells, the malondialdehyde content increased, whereas the vitamin C, dialdehyde, flavonoid and total phenol contents decreased. Polyphenol oxidase, superoxide dismutase, catalase, peroxidase, ascorbate peroxidase and ammonia lyase activities also decreased. Overall, these findings demonstrated that B. velezensis zk1 infection damaged peach chloroplasts, mitochondria, respiratory chain activity and related free radical scavenging enzyme systems, thereby disrupting the normal physiological metabolism of peaches and causing rot.
Effect of nitrate reduction and storage time on the antioxidative properties, biogenic amines and amino acid profile of dry fermented loins
Authors: Karwowska Małgorzata , Kononiuk Anna D.
Published: September 2021

The aim of this work was to evaluate the effect of nitrate reduction and storage time on the content of amino acids and biogenic amines (BAs), total antioxidant capacity (TAC) and antioxidative properties of peptides isolated from dry fermented loins. The results showed that reducing the addition of nitrates increased the amount of BAs formed during storage of dry fermented loins. The lowest TAC value (tested by ABTS assay) was recorded for the sample with the highest nitrate addition (150 mg kg‐1) at beginning, while the highest value was noted for the sample without nitrate addition at 180 days of storage. The amino acid profile showed that dry fermented loin with the highest addition of nitrate was characterised by a significantly lower content of amino acids, which are precursors of key aroma compounds compared with loin samples with a lower amount of added sodium nitrate. The sum of ranking differences (SRD) indicated that loin sample with traditional addition of nitrate (150 mg kg‐1) after 120 days of storage was characterised by the lowest SRD result, which means that they are the closest to the assumed values, that is the lowest content of BAs, the highest antioxidant activity and amino acid patterns recommended by WHO/FAO/UNU Experts.