bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrograde mechanism coordinates memory allocation across brain regions
Authors: Lavi Ayal , Sehgal Megha , Sisan Fardad , Okabe Anna , Ter-Mkrtchyan Donara , Silva Alcino J
Published: November 2021

Memories engage ensembles of neurons across different brain regions within a memory system. However, it is unclear whether the allocation of a memory to these ensembles is coordinated across brain regions. To address this question, we used CREB expression to bias memory allocation in one brain region, and rabies retrograde tracing to test memory allocation in connected presynaptic neurons in the other brain regions. We find that biasing allocation of CTA memory in the basolateral amygdala (BLA) also biases memory allocation in presynaptic neurons of the insular cortex (IC). By manipulating the allocation of CTA memory to specific neurons in both BLA and IC, we found that we increased their connectivity and enhanced CTA memory performance. These results – which are corroborated by mathematical simulations, and by studies with auditory fear conditioning – demonstrate that a retrograde mechanism coordinates the allocation of memories across different brain regions.
Development and Validation of Subject-Specific 3D Human Head Models Based on a Nonlinear Visco-Hyperelastic Constitutive Framework
Authors: Upadhyay Kshitiz , Alshareef Ahmed , Knutsen Andrew K. , Johnson Curtis L. , Carass Aaron , Bayly Philip V. , Ramesh K.T.
Published: November 2021

Computational models of the human head are promising tools for the study and prediction of traumatic brain injuries (TBIs). Most available head models are developed using inputs (i.e., head geometry, material properties, and boundary conditions) derived from ex-vivo experiments on cadavers or animals and employ linear viscoelasticity (LVE)-based constitutive models, which leads to high uncertainty and poor accuracy in capturing the nonlinear response of brain tissue under impulsive loading conditions. To resolve these issues, a framework for the development of fully subject-specific 3D human head models is proposed, in which model inputs are derived from the same living human subject using a comprehensive in-vivo brain imaging protocol, and the viscous dissipation-based visco-hyperelastic constitutive modeling framework is employed. Specifically, brain tissue material properties are derived from in-vivo magnetic resonance elastography (MRE), and full-field strain-response of brain under rapid rotational acceleration is obtained from tagged MRI, which is used for model validation. The constitutive model comprises the Ogden hyperelastic strain energy density and the Upadhyay-Subhash-Spearot viscous dissipation potential. The simulated strain-response is compared with experimental data and with predictions from subject-specific models employing two commonly used LVE-based constitutive models, using a rigorous validation procedure that evaluates agreement in spatial strain distribution, temporal strain evolution, and differences in maximum values of peak and average strain. Results show that the head model developed in this work reasonably captures 3D brain dynamics, and when compared to LVE-based models, provides improvements in the prediction of peak strains and temporal strain evolution.
A macromutation eliminates colour patterning in captive butterflies
Authors: Hanly Joseph J. , Livraghi Luca , Heryanto Christa , McMillan W. Owen , Jiggins Chris D. , Gilbert Lawrence E. , Martin Arnaud
Published: November 2021

Captive populations often harbor variation that is not present in the wild due to artificial selection. Recent efforts to map this variation have provided insights into the genetic and molecular basis of variation. Heliconius butterflies display a large array of pattern variants in the wild and the genetic basis of these patterns has been well-described. Here we sought to identify the genetic basis of an unusual pattern variant that is instead found in captivity, the ivory mutant, in which all scales on both the wings and body become white or yellow. Using a combination of autozygosity mapping and coverage analysis from 37 captive individuals, we identify a 78kb deletion at the cortex wing patterning locus as the ivory mutation. This deletion is undetected among 458 wild Heliconius genomes samples, and its dosage explains both homozygous and heterozygous ivory phenotypes found in captivity. The deletion spans a large 5’ region of the cortex gene that includes a facultative 5’UTR exon detected in larval wing disk transcriptomes. CRISPR mutagenesis of this exon replicates the wing phenotypes from coding knock-outs of cortex, consistent with a functional role of ivory-deleted elements in establishing scale color fate. Population demographics reveal that the stock giving rise to the ivory mutant has a mixed origin from across the wild range of H. melpomene, and supports a scenario where the ivory mutation occurred after the introduction of cortex haplotypes from Ecuador. Homozygotes for the ivory deletion are inviable, joining 40 other examples of allelic variants that provide heterozygous advantage in animal populations under artificial selection by fanciers and breeders. Finally, our results highlight the promise of autozygosity and association mapping for identifying the genetic basis of aberrant mutations in captive insect populations.
Particle interactions and their effect on magnetic particle imaging and spectroscopy
Authors: Moor Lorena , Scheibler Subas , Gerken Lukas , Scheffler Konrad , Thieben Florian , Knopp Tobias , Herrmann Inge K. , Starsich Fabian H. L.
Published: November 2021

Tracer and thus signal stability is crucial for an accurate diagnosis via magnetic particle imaging (MPI). However, MPI-tracer nanoparticles frequently agglomerate during their in vivo applications leading to particle interactions. Here, we investigate the influence of such magnetic coupling phenomena on the MPI signal. We prepared and characterized Zn0.4Fe2.6O4 nanoparticles and controlled their interparticle distance by variying SiO2 coating thickness. The silica shell affected the magnetic properties indicating stronger particle interactions for a smaller interparticle distance. The SiO2-coated Zn0.4Fe2.6O4 outperformed the bare sample in magnetic particle spectroscopy (MPS) in terms of signal/noise, however, the shell thickness itself only weakly influenced the MPS signal. To investigate the importance of magnetic coupling effects in more detail, we benchmarked the MPS signal of the bare and SiO2-coated Zn-ferrites against commercially available PVP-coated Fe3O4 nanoparticles in water and PBS. PBS is known to destabilize nanoparticles mimicking an agglomeration in vivo. The bare and coated Zn-ferrites showed excellent signal stability, despite their agglomeration in PBS. We attribute this to their aggregated morphology formed during their flame-synthesis. On the other hand, the MPS signal of commercial PVP-coated Fe3O4 strongly decreased in PBS compared to water, indicating strongly changed particle interactions. The relevance of this effect was further investigated in a mammalian cell model. For PVP-coated Fe3O4, we could detect a strong discrepancy between the particle concentration obtained from the MPS signal and the actual concentration determined via ICP-MS. The same trend was observed during their MPI analysis; while SiO2-coated Zn-ferrites could be precisely located in water and PBS, PVP-coated Fe3O4 could not be detected in PBS at all. This drastically limits the sensitivity and also general applicability of MPI using such standard commercial tracers and highlights the advantages of our flame-made Zn-ferrites concerning signal stability and ultimately diagnostic accuracy.
Biophysically inspired mean-field model of neuronal populations driven by ion exchange mechanisms
Authors: Rabuffo Giovanni , Bandyopadhyay Abhirup , Calabrese Carmela , Gudibanda Kashyap , Depannemaecker Damien , Takarabe Lavinia Mitiko , Saggio Maria Luisa , Desroches Mathieu , Ivanov Anton I , Linne Marja-Leena , bernard christophe , Petkoski Spase , Jirsa Viktor
Published: November 2021

Whole-brain simulations are a valuable tool for gaining insight into the multiscale processes that regulate brain activity. Due to the complexity of the brain, it is impractical to include all microscopic details in a simulation. Hence, researchers often simulate the brain as a network of coupled neural masses, each described by a mean-field model. These models capture the essential features of neuronal populations while approximating most biophysical details. However, it may be important to include certain parameters that significantly impact brain function. The concentration of ions in the extracellular space is one key factor to consider, as its fluctuations can be associated with healthy and pathological brain states. In this paper, we develop a new mean-field model of a population of Hodgkin-Huxley-type neurons, retaining a microscopic perspective on the ion-exchange mechanisms driving neuronal activity. This allows us to maintain biophysical interpretability while bridging the gap between micro and macro-scale mechanisms. Our model is able to reproduce a wide range of activity patterns, also observed in large neural network simulations. Specifically, slow-changing ion concentrations modulate the fast neuroelectric activity, a feature of our model that we validated through in vitro experiments. By studying how changes in extracellular ionic conditions can affect whole-brain dynamics, this model serves as a foundation to measure biomarkers of pathological activity and provide potential therapeutic targets in cases of brain dysfunctions like epilepsy.
Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike
Authors: Díaz-Salinas Marco A. , Li Qi , Ejemel Monir , Yurkovetskiy Leonid , Luban Jeremy , Shen Kuang , Wang Yang , Munro James B.
Published: November 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells through binding to angiotensin-converting enzyme 2 (ACE2). This interaction is mediated by the receptor-binding domain (RBD) of the viral spike (S) glycoprotein. Structural and dynamic data have shown that S can adopt multiple conformations, which controls the exposure of the ACE2-binding site in the RBD. Here, using single-molecule Förster resonance energy transfer (smFRET) imaging we report the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and the B.1 variant (D614G). We find that D614G modulates the energetics of the RBD position in a manner similar to ACE2 binding. We also find that antibodies that target diverse epitopes, including those distal to the RBD, stabilize the RBD in a position competent for ACE2 binding. Parallel solution-based binding experiments using fluorescence correlation spectroscopy (FCS) indicate antibody-mediated enhancement of ACE2 binding. These findings inform on novel strategies for therapeutic antibody cocktails.
Joint modeling of choices and reaction times based on Bayesian contextual behavioral control
Authors: Schwöbel Sarah , Markovic Dimitrije , Smolka Michael N. , Kiebel Stefan
Published: November 2021

In cognitive neuroscience and psychology, reaction times are an important behavioral measure. However, in instrumental learning and goal-directed decision making experiments, findings often rely only on choice probabilities from a value-based model, instead of reaction times. Recent advancements have shown that it is possible to connect value-based decision models with reaction time models. However, typically these models do not provide an integrated account of both value-based choices and reaction times, but simply link two types of models. Here, we propose a novel integrative joint model of both choices and reaction times by combining a mechanistic account of Bayesian sequential decision making with a sampling procedure. This allows us to describe how internal uncertainty in the planning process shapes reaction time distributions. Specifically, we use a recent context-specific Bayesian forward planning model which we extend by a Markov chain Monte Carlo (MCMC) sampler to obtain both choices and reaction times. As we will show this makes the sampler an integral part of the decision making process and enables us to reproduce, using simulations, well-known experimental findings in value based-decision making as well as classical inhibition and switching tasks. Specifically, we use the proposed model to explain both choice behavior and reaction times in instrumental learning and automatized behavior, in the Eriksen flanker task and in task switching. These findings show that the proposed joint behavioral model may describe common underlying processes in these different decision making paradigms.

Author summary

Many influential results in psychology and cognitive neuroscience rest on reaction time effects in behavioral experiments, for example in studies about human decision making. For decisions that rest on planning, findings often rely on analyses using specific computational models. Until recently, these models did not allow for analysis of reaction times. In this article we introduce a new model of how to explain both choices and reaction times in decision making experiments that involve planning. Importantly, the model explains how the brain can make good decisions quickly, even in the face of many potential choices and in complex environments.
Selective Control of Synaptically-Connected Circuit Elements by All-Optical Synapses
Authors: Prakash Mansi , Murphy Jeremy , St Laurent Robyn , Friedman Nina , Crespo Emmanuel L. , Bjorefeldt Andreas , Pal Akash , Bhagat Yuvraj , Kauer Julie A. , Shaner Nathan C. , Lipscombe Diane , Moore Christopher I. , Hochgeschwender Ute
Published: November 2021

Understanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using bioluminescent light: Luciferase-generated light, originating from a presynaptic axon terminal, modulates an opsin in its postsynaptic target. Vesicular-localized luciferase is released into the synaptic cleft in response to presynaptic activity, creating a real-time ‘Optical Synapse’. Light production is under experimenter-control by introduction of the small molecule luciferin. Signal transmission across this optical synapse is temporally defined by the presence of both the luciferin and presynaptic activity. We validate synaptic ‘Interluminescence’ by multi-electrode recording in cultured neurons and in mice in vivo. Interluminescence represents a powerful approach to achieve synapse-specific and activity-dependent circuit control during behavior in vivo.
Inflammasome-related markers at the ICU admission are not associated with outcome in the critically ill COVID-19 patients
Authors: Adamik Barbara , Ambrożek-Latecka Magdalena , Dragan Barbara , Jeznach Aldona , Śmiechowicz Jakub , Goździk Waldemar , Skirecki Tomasz
Published: November 2021

Purpose

Development of targeted biological therapies for COVID-19 requires reliable biomarkers that could help indicate the responding patients. Hyperactivation of the inflammasome by SARS-CoV2 virus is hypothesized to contribute to severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins at the admission to the intensive care unit (ICU).

Patients and methods

Plasma samples were obtained from 45 critically ill COVID-19 patients and from 10 patients any without any signs of infection (TBI, traumatic brain injury) on admission to the ICU. The concentration of IL-1α, IL-1β, IL-18, IL-1RA, galectin-1, ASC, LDH, ferritin, and gasdermin D were analyzed. A novel cell-free caspase-1 plasma assay was developed by inhibitor-based immunoprecipitation followed by Western Blot. Demographic and clinical characteristics were recorded.

Results

In-hospital mortality in COVID-19 patients reached 62%. Galectin-1 was 1.8-fold lower in COVID-19 than in TBI patients (17101.84 vs. 30764.20 pg/ml, p=0.007), but other inflammasome-related biomarkers were at similar concentrations. Patients with SOFA score of >9 on admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison to low-risk patients (25551.3 pg/ml vs 16302.7 pg/ml, p=0.014; 14.5 pg/ml vs 39.4 pg/ml, p=0.04, respectively). Statistically significant correlations were observed between: IL-1α and platelets (r=-0.37), IL-1β and platelets (r=-0.36), ferritin and INR (r=0.39). Activated caspase-1 p35 was detectable in 12/22 COVID-19 patients but in none of the TBI patients. Its presence was related with higher fibrinogen and lower D-dimers. Moreover, the densitometric analysis showed a significantly higher amount of p35 in patients with SOFA> 9.

Conclusion

Our results indicate that the systemic markers of activation of the inflammasome in critically ill COVID-19 patients is not directly related with outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.
Pay-it-forward to improve influenza vaccine uptake and public engagement among children and older adults in China: A quasi-experimental pragmatic trial
Authors: Wu Dan , Jin Chenqi , Bessame Khaoula , Tang Fanny Fong-Yi , Ong Jason J. , Wang Zaisheng , Xie Yewei , Jit Mark , Larson Heidi J. , Chantler Tracey , Lin Leesa , Gong Wenfeng , Yang Fan , Jing Fengshi , Wei Shufang , Cheng Weibin , Zhou Yi , Ren Nina , Qiu Shuhao , Bao Jianmin , Wen Liufen , Yang Qinlu , Tian Junzhang , Tang Weiming , Tucker Joseph D.
Published: November 2021

Background

China has low seasonal influenza vaccination rates among children and older adults. This quasi-experimental pragmatic trial examined the effectiveness of a pay-it-forward intervention on influenza vaccination compared to standard-of-care (user-paid vaccination) among children and older people in China. Pay-it-forward offered a free influenza vaccine from a local group and an opportunity to donate financially to support future individuals.

Methods

At each of the three study sites, participants were recruited into the standard-of-care arm first until expected sample size was reached and then recruited into the pay-it-forward arm. The primary outcome was vaccine uptake. Secondary outcomes included vaccine confidence and costs. Regression methods compared influenza vaccine uptake and vaccine confidence between the two arms.

Results

Among 300 participants enrolled, 55/150(36.7%) in the standard-of-care arm 111/150(74.0%) in the pay-it-forward arm received an influenza vaccine. People in the pay-it-forward arm were more likely to receive the vaccine compared to people in the standard-of-care arm (adjusted odds ratio (aOR)= 6.7, 95%CI [2.7, 16.6] among children; aOR=5.0, [2.3, 10.8] among older adults). People in the pay-it-forward arm had greater confidence in vaccine safety, importance, and effectiveness. In the pay-it-forward arm, 107/111 (96.4%) of participants donated money for subsequent vaccinations, and 19 of 60 invited (31.7%) created postcard messages. The pay-it-forward arm had a lower economic cost per person vaccinated ($45.60) than the standard-of-care arm ($64.67).

Conclusions

Pay-it-forward was effective in improving influenza vaccine uptake and public engagement. Our data have implications for pro-social interventions to enhance influenza vaccine uptake in countries where influenza vaccines are available for a fee.

Trial registration

ChiCTR2000040048

Main point summary

Pay-it-forward substantially increased influenza vaccine uptake among children and older adults compared to standard of care user-paid vaccination.
Gigavalent display of proteins on monodisperse polyacrylamide hydrogels as a versatile modular platform for functional assays and protein engineering
Authors: Fryer Thomas , Rogers Joel David , Mellor Christopher , Minter Ralph , Hollfelder Florian
Published: November 2021

The robust modularity of biological components that are assembled into complex functional systems is central to synthetic biology. Here we apply modular “plug and play” design principles to a microscale solid phase protein display system that enables protein purification and functional assays for biotherapeutics. Specifically, we capture protein molecules from cell lysates on polyacrylamide hydrogel display beads (‘PHD beads’), made in microfluidic droplet generators. These monodisperse PHD beads are decorated with predefined amounts of anchors, methacrylate-PEG-benzylguanine (BG) and methacrylate-PEG-chloroalkane (CA). Anchors form covalent bonds with fusion proteins bearing cognate tag recognition (SNAP and Halo-tags) in specific, orthogonal and stable fashion. Given that these anchors are copolymerised throughout the 3D structure of the beads, proteins are also distributed across the entire bead sphere, allowing attachment of ∼109 protein molecules per bead (Ø 20 μm). This mode of attachment reaches a higher density than possible on widely used surface-modified beads, and additionally mitigates surface effects that often complicate studies with proteins on beads. We showcase a diverse array of protein modules that enable the secondary capture of proteins, either non-covalently (IgG and SUMO-tag) or covalently (SpyCatcher, SpyTag, SnpCatcher and SnpTag). Proteins can be displayed in their monomeric forms, but also reformatted as a multivalent display (using secondary capture modules that create branches) to test the contributions of avidity and multivalency towards protein function. Finally, controlled release of modules by irradiation of light is achieved by incorporating the photocleavable protein PhoCl: irradiation severs the displayed protein from the solid support, so that functional assays can be carried out in solution. As a demonstration of the utility of valency engineering, an antibody drug screen is performed, in which an anti-TRAIL-R1 scFv protein is released into solution as monomers-hexamers, showing a ∼50-fold enhanced potency in the pentavalent format. The ease of protein purification on solid support, quantitative control over presentation and release of proteins and choice of valency make this experimental format a versatile, modular platform for large scale functional analysis of proteins, in bioassays of protein-protein interactions, enzymatic catalysis and bacteriolysis.

Table of Contents Graphics
Plasma donation induces a protein expression profile shift in circulating human blood
Authors: Flickenger Rob
Published: November 2021

Commercial plasma donation yields a change in protein concentration similar to that observed in therapeutic plasma exchange (TPE) in humans. The post-donation expression profile shows an increase in many proteins after even a single donation, and the effect is enhanced with additional donations. Unlike TPE, human plasma donation returns saline without albumin to the donor, thus eliminating supplemental albumin as a contributing factor. The observed fold change falls outside the variation expected by natural circadian expression changes.

N=6 humans (four donors, one monthly control and one circadian test). Seventeen antibody tests were performed, measuring the concentration of 507 proteins for each test.
Study Protocol of A Phase II Study to Evaluate Safety and Efficacy of Neo-adjuvant Pembrolizumab and Radiotherapy in Localized Rectal Cancer
Authors: Corrò Claudia , Buchs Nicolas C. , Tihy Matthieu , Durham-Faivre André , Bichard Philippe , Frossard Jean-Louis , Puppa Giacomo , McKee Thomas , Roth Arnaud , Zilli Thomas , Trembleau Christelle , Marco Mariagrazia Di , Dutoit Valérie , Dietrich Pierre-Yves , Ris Frédéric , Kössler Thibaud
Published: November 2021

Background

Reshaping the tumor microenvironment by novel immunotherapies represents a key strategy to improve the treatment of cancers. Nevertheless, responsiveness to these treatments is often correlated with the extent of the T cell infiltration at the tumor site. Remarkably, microsatellite stable rectal cancer is characterized by poor infiltration and, therefore, do not respond to immune checkpoint blockade. To date, the only available curative option for these patients relies on extensive surgery. With the aim to broaden the application of promising immunotherapies, it is necessary to develop alternative approaches to promote T cell infiltration into the tumor microenvironment of these tumors. In this regard, recent evidence shows that radiotherapy may have profound immunostimulatory effects, hinting at the possibility of combining it with immunotherapy. The combination of long-course chemoradiotherapy and immunotherapy was recently shown to be safe and yielded promising results in rectal cancer, however short-course radiotherapy and immunotherapy have never been tested in these tumors.

Methods

Our clinical trial investigates the clinical and biological impact of combining pembrolizumab with short-course radiotherapy in the neo-adjuvant treatment of localized microsatellite stable rectal cancer. This phase II non-randomized study will recruit 25 patients who will receive short-course preoperative radiotherapy (5Gy x 5 days) and four injections of pembrolizumab starting on the same day and on weeks 4, 7 and 10. Radical surgery will be performed after three weeks from the last pembrolizumab injection. Our clinical trial also includes an extensive research program involving the transcriptomic and proteomic analysis of blood and tumor samples throughout the course of the treatment.

Discussion

Our study is the first clinical trial to provide with safety and efficacy information of this novel treatment approach in rectal cancer, leading to a major breakthrough in the treatment of this cancer. Additionally, the translational research program will offer better insight into immunological changes within the tumor and blood during treatment. Taken together, our work will help optimizing future treatment combinations and, possibly, better selecting patients.

Trial registration

This study was registered with www.clinicaltrial.gov: NCT04109755. Registration date: June, 2020.
Polyamines mediate enterovirus attachment directly and indirectly through cellular heparan sulfate synthesis
Authors: Hulsebosch Bridget M. , Omoba Oreoluwa S. , LoMascolo Natalie J. , Mounce Bryan C.
Published: November 2021

Productive viral infection begins with attachment to a susceptible cell, and viruses have evolved complex mechanisms to attach to and subsequently enter cells. Prior to engagement with a cellular receptor, viruses frequently interact with nonspecific attachment factors that can facilitate virus-receptor interactions and viral entry. Polyamines, small positively-charged molecules abundant in mammalian cells, mediate viral attachment, though the mechanism was not fully understood. Using the Coxsackievirus B3 (CVB3) enterovirus model system, we show that polyamines mediate viral attachment both directly and indirectly. The polyamine putrescine specifically enhances viral attachment to cells depleted of polyamines. Putrescine’s positive charge mediates its ability to enhance viral attachment, and polyamine analogs are less efficient at mediating viral attachment. In addition to this direct role of polyamines in attachment, polyamines facilitate the cellular expression of heparan sulfates, negatively-charged molecules found on the cell surface. In polyamine-depleted cells, heparan sulfates are depleted from the surface of cells, resulting in reduced viral attachment. We find that this is due to polyamines’ role in the process of hypusination of eukaryotic initiation factor 5A, which facilitates cellular translation. These data highlight the important role of polyamines in mediating cellular attachment, as well as their function in facilitating cellular heparan sulfate synthesis.
Synthetic periphyton as a model system to understand species dynamics in complex microbial freshwater communities
Authors: Lamprecht Olga , Wagner Bettina , Derlon Nicolas , Tlili Ahmed
Published: November 2021

Phototrophic biofilms, also known as periphyton, are microbial freshwater communities that drive crucial ecological processes in streams and lakes. Gaining a deep mechanistic understanding of the biological processes occurring in natural periphyton remains challenging due to the high complexity and variability of such communities. To address this challenge, we rationally developed a workflow to construct a synthetic community by co-culturing 26 phototrophic species (i.e., diatoms, green algae and cyanobacteria) that were inoculated in a successional sequence to create a periphytic biofilm on glass slides. We show that this community is diverse, stable and highly reproducible in terms of microbial composition, function and 3D spatial structure of the biofilm. We also demonstrate the ability to monitor microbial dynamics at the single species level during periphyton development and how their abundances are impacted by stressors such as increased temperature and a herbicide, singly and in combination. Overall, such a synthetic periphyton, grown under controlled conditions, can be used as a model system for theory testing through targeted manipulation.
Intestinal GCN2 controls Drosophila systemic growth in response toLactiplantibacillus plantarumsymbiotic cues encoded by r/tRNA operons
Authors: Grenier T. , Consuegra J. , Galvao Ferrarini M. , Akherraz H. , Bai L. , Dusabyinema Y. , Rahioui I. , da Silva P. , Gillet B. , Hughes S. , Ramos C. , Matos RC. , Leulier F.
Published: November 2021

Symbiotic bacteria interact with their host through symbiotic cues. Here, we took advantage of the mutualism between Drosophila andLactiplantibacillus plantarum(Lp) to investigate a novel mechanism of host-symbiont interaction. Using chemically-defined diets, we found that association with Lp improves the growth of larvae fed amino acid-imbalanced diets, even though Lp cannot produce the limiting amino acid. We show that in this context Lp supports its host’s growth through a molecular dialog that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the GCN2 kinase in Drosophila’s enterocytes. Our data indicate Lp’s r/tRNAs are packaged in extracellular vesicles and activate GCN2 in a subset of larval enterocytes, a mechanism necessary to remodel the intestinal transcriptome and ultimately to support anabolic growth. Based on our findings, we propose a novel beneficial molecular dialog between host and microbes, which relies on a non-canonical role of GCN2 as a mediator of non-nutritional symbiotic cues encoded by r/tRNA operons.
A temperature sensitive mutation in the CstF77 subunit of the polyadenylation complex reveals the critical function of mRNA 3’ end formation for a robust heat stress response in plants
Authors: Kim Minsoo , Swenson John , McLoughlin Fionn , Vierling Elizabeth
Published: November 2021

Background

Heat Shock Protein 101 (HSP101) in plants and orthologs in bacteria (Caseinolytic peptidase B, ClpB) and yeast (Hsp104) are essential for thermotolerance. To investigate molecular mechanisms of thermotolerance involving HSP101, we performed a suppressor screen in Arabidopsis thaliana of a semi-dominant, missense HSP101 allele, hot1-4 (A499T). Plants carrying the hot1-4 mutation are more heat-sensitive than an HSP101 null mutant (hot1-3), indicating the toxicity of hot1-4 allele.

Results

We report that one suppressor (shot2, suppressor of hot1-4 2) has a temperature-sensitive, missense mutation (E170K) in the CstF77 (Cleavage stimulation factor 77) subunit of the polyadenylation complex, which is critical for 3’ end maturation of pre-mRNA. RNA-Seq analysis of total RNA depleted of ribosomes reveals that heat treatment causes transcriptional readthrough events in shot2, specifically in highly heat-induced genes, including the toxic hot1-4 gene. In addition, failure of correct transcript processing leads to reduced accumulation of many HSP RNAs and proteins, suppressing heat sensitivity of the hot1-4 mutant, due to reduction of the toxic mutant HSP101 protein. Notably, the shot2 mutation makes plants more sensitive to heat stress in the HSP101 null (hot1-3) and wild-type backgrounds correlated with the reduced expression of other heat-inducible genes required for thermotolerance.

Conclusions

Our study reveals the critical function of CstF77 for 3’ end formation of mRNA during heat stress, as well as the dominant role of HSP101 in dictating the outcome of severe heat stress in plants.
Sentinels of chromatin: chromodomain helicase DNA-binding proteins in development and disease
Authors: Alendar Andrej , Berns Anton
Published: November 2021

Chromatin is highly dynamic, undergoing continuous global changes in its structure and type of histone and DNA modifications governed by processes such as transcription, repair, replication, and recombination. Members of the chromodomain helicase DNA-binding (CHD) family of enzymes are ATP-dependent chromatin remodelers that are intimately involved in the regulation of chromatin dynamics, altering nucleosomal structure and DNA accessibility. Genetic studies in yeast, fruit flies, zebrafish, and mice underscore essential roles of CHD enzymes in regulating cellular fate and identity, as well as proper embryonic development. With the advent of next-generation sequencing, evidence is emerging that these enzymes are subjected to frequent DNA copy number alterations or mutations and show aberrant expression in malignancies and other human diseases. As such, they might prove to be valuable biomarkers or targets for therapeutic intervention.
Can paternalistic leaders enhance knowledge sharing? The roles of organizational commitment and Islamic work ethics
Authors: Chaudhary Arooba , Islam Talat , Ali Hafiz Fawad , Jamil Saqib
Published: November 2021

Purpose

This paper aims to investigate the effect of paternalistic leadership (benevolent, moral and authoritarian) on knowledge sharing of nurses through the mediation of organizational commitment (affective, continuance and normative). Further, the study examines the moderating role of Islamic work ethics on the association between organizational commitment and knowledge sharing.

Design/methodology/approach

In this quantitative study, data was collected from 312 nurses working in the health-care sector of Pakistan through “Google Forms” in two waves. Moreover, structural equation modeling was used to test the proposed hypotheses.

Findings

The study noted affective and normative commitment as mediators between the associations of benevolent, moral and authoritarian leadership with knowledge sharing, whereas continuance commitment was not found as an explaining variable. In addition, Islamic work ethics was found to strengthen the association of affective and normative commitment with knowledge sharing. However, Islamic work ethics was found to weaken the association between continuance commitment and knowledge sharing.

Practical implications

This study offers practical insights for health-care executives to act as fatherly figures to enhance the knowledge sharing of their nurses. The study recommends that managers in the health-care system build such an environment that helps nurses follow Islamic work ethics. It may enhance their level of organizational commitment and encourage them to engage in knowledge sharing behaviors to have a successful work environment.

Originality/value

To the best of the authors’ knowledge, this research is the first to extend the literature on paternalistic leadership. More specifically, this study investigated how various dimensions of paternalistic leadership (benevolent, moral and authoritarian) effects three-dimensional commitment (affective, continuance and normative) to enhance knowledge sharing behavior among nurses.
A comparative analysis on the single-phase and two-phase mixture models for calculation of ferrofluid convective heat transfer in the presence of a magnetic field: a numerical study
Authors: Jafari Hamed , Goharkhah Mohammad , Mahdavi Nejad Alireza
Published: November 2021

Purpose

This paper aims to analyze the accuracy of the single and two-phase numerical methods for calculation of ferrofluid convective heat transfer in the presence of a magnetic field. The findings of current study are compared with previous single-phase numerical results and experimental data. Accordingly, the effect of various parameters including nanoparticles concentration, Reynolds number and magnetic field strength on the performance of the single and two-phase models are evaluated.

Design/methodology/approach

A two-phase mixture numerical study is carried out to investigate the influence of four U-shaped electromagnets on the hydrodynamic and thermal characteristics of Fe3O4/Water ferrofluid flowing inside a heated channel.

Findings

It is observed that the applied external magnetic field signifies the convective heat transfer from the channel surface, despite local reduction at a few locations. The maximum heat transfer enhancement is predicted as 23% and 25% using single and two-phase models, respectively. The difference between the results of the two models is mainly attributed to the slip velocity effect which is accounted for in the two-phase model. The magnetic field gradient leads to a significant increase in the slip velocity which in turn causes a slight difference in velocity and temperature profiles obtained by the single and two-phase models in the magnetic field region. According to percentage error calculation, the two-phase method is generally more accurate than the single-phase method. However, the percentage error of both models improves by decreasing either magnetic field intensity or Reynolds number.

Originality/value

For the first time in the literature, to the best of the authors’ knowledge, the current work analyzes the accuracy of the single and two phase numerical methods for calculation of ferrofluid convective heat transfer in the presence of a magnetic field.
Circles of analysis: a systemic model of child criminal exploitation
Authors: Barlow Craig , Kidd Alicia , Green Simon T. , Darby Bethany
Published: November 2021

Purpose

Child criminal exploitation (CCE) emerges from the complex interplay between potential targets, motivated perpetrators and conducive environments. Drawing on contextual safeguarding and rational choice theory. The purpose of this paper is to explain the relational dynamics that lead to CCE in terms of complex systems.

Design/methodology/approach

This paper reviews the existing criminological and public health perspectives on CCE and compare against current assessment protocols used to identify child victims of exploitation.

Findings

Findings demonstrate a conceptual and empirical flaw in existing practice. This flaw can be understood in terms of a failure to include both environmental conditions and the perpetrator’s motivation when trying to prevent CCE.

Research limitations/implications

To correct this, this paper develops an original systemic model called circles of analysis. This model builds on contextual safeguarding to overcome this identified flaw by also including perpetrator motivation to develop a Systemic Investigation, Protection and Prosecution Strategy.

Practical implications

It is worth considering as to whether our model can be scaled up to look at trafficking of children and adults for modern slavery, servitude, forced and compulsory labour in different contexts and jurisdictions. Alongside this, is there capacity to build perpetrator behaviours into the contextual safeguarding model?

Social implications

The potential for further development and alignment with the principles of contextual safeguarding is tantalising, and it is hoped that the contribution to this important special edition will open up new avenues for collaboration with both academics and practitioners who are concerned with protecting children and combatting CCE.

Originality/value

This strategy is uniquely designed to improve how police and social workers identify and investigate CCE and safeguard potential victims and survivors.
Increasing non-oil revenue potentiality through digital commerce: the case study in KSA
Authors: Al-Khalidi Al-Maliki Saeed Q.
Published: November 2021

Purpose

This study mainly focuses on the potentiality of the e-commerce industry's opportunities and limitations in the Kingdom of Saudi Arabia (KSA) specifically toward non-oil revenue sectors.

Design/methodology/approach

E-commerce contribution to the retail market industry becomes more global and more flexible with the rapid growth of the Internet and information technology revolution. A new way of conducting business is rendered by e-commerce, which helps to make a profit electronically.

Findings

The main contributions of e-commerce are management of company operations, easy and cheaper ways of extending their markets and coordinating with the value chain across different borders. In addition, the Internet and e-commerce are responsible for removing language barriers, cultural diversification and extending the market to the national boundaries. The countries would have many innovative and dynamic aspects by the beginning of the global market that increases national revenue, market, employment opportunity, capital and access to technology and information.

Originality/value

At present, KSA's national revenue mostly depends on oil and its related commodities, while other trades compete with the global market and increase national income. So, it is essential to increase other Saudi products to reach a global business level through e-commerce. Moreover, the study suggests accessing new markets and participating in global production to improve e-commerce structure without affecting current employment patterns, industry structure, productivity and Saudi culture.
Analysis of sales and financing modes in a green platform supply chain with a capital-constrained manufacturer
Authors: Wang Jun , Yao Song , Wang Xin , Hou Pengwen , Zhang Qian
Published: November 2021

Purpose

The purpose of this paper is to investigate the optimal operational strategies in a green platform supply chain and provide suggestions on the selection of sales and financing modes for the capital-constrained manufacturer.

Design/methodology/approach

This study combines different sales channels with financing modes and investigates three sales-financing modes, i.e. traditional sales-prepayment financing (TSPF), traditional sales-bank financing (TSBF) and online sales e-retailer financing (OSEF). By establishing and comparing Stackelberg game models of these sales-financing modes from the perspectives of economy, environment and social welfare, the optimal strategies of emission reduction, financing, pricing and service improvement are obtained.

Findings

The results suggest that as the commission rate increases to a certain level, a threshold of the cost coefficient of emission reduction can be found such that the manufacturer should choose OSEF below this threshold and TSBF above this threshold. OSEF is Pareto optimal when this cost coefficient is low, and this mode can lead to the highest social welfare when the platform loan interest rate is relatively low. The Pareto areas in TSBF and OSEF enlarge as the default coefficient decreases.

Practical implications

These results can provide operational insights on how to select sales channels and financing modes when manufacturer faces financial constraints in emission reduction.

Originality/value

This paper combines different sales and financing modes to study their comprehensive influence on the decision-makings of chain members and the resulting performance of economy, environment and social welfare.
An optimisation framework for designs for additive manufacturing combining design, manufacturing and post-processing
Authors: Wiberg Anton , Persson Johan , Ölvander Johan
Published: November 2021

Purpose

The purpose of this paper is to present a Design for Additive Manufacturing (DfAM) methodology that connects several methods, from geometrical design to post-process selection, into a common optimisation framework.

Design/methodology/approach

A design methodology is formulated and tested in a case study. The outcome of the case study is analysed by comparing the obtained results with alternative designs achieved by using other design methods. The design process in the case study and the potential of the method to be used in different settings are also discussed. Finally, the work is concluded by stating the main contribution of the paper and highlighting where further research is needed.

Findings

The proposed method is implemented in a novel framework which is applied to a physical component in the case study. The component is a structural aircraft part that was designed to minimise weight while respecting several static and fatigue structural load cases. An addition goal is to minimise the manufacturing cost. Designs optimised for manufacturing by two different AM machines (EOS M400 and Arcam Q20+), with and without post-processing (centrifugal finishing) are considered. The designs achieved in this study show a significant reduction in both weight and cost compared to one AM manufactured geometry designed using more conventional methods and one design milled in aluminium.

Originality/value

The method in this paper allows for the holistic design and optimisation of components while considering manufacturability, cost and component functionality. Within the same framework, designs optimised for different setups of AM machines and post-processing can be automatically evaluated without any additional manual work.
Clinical characteristics of Japanese pustular psoriasis: A multicenter observational study
Authors: Ohata Chika , Tsuruta Noriko , Yonekura Kentaro , Higashi Yuko , Saito Kanami , Katayama Eri , Imafuku Shinichi ,   Western Japan Inflammatory Disease Research Group
Published: November 2021

Generalized pustular psoriasis (GPP) is a rare and severe subtype of psoriasis. Because of its rarity, GPP studies with a large sample size have been scarce. We studied the characteristics of GPP and pustular psoriasis using data from the West Japan Psoriasis Registry that had been registered until the end of December 2020. The dataset included 104 patients with pustular psoriasis and 1290 patients with other subtypes of psoriasis. Multivariate analysis revealed a significantly greater number of female patients, a significantly lower mean body mass index, and a significantly lower ratio of habitual drinkers in pustular psoriasis, compared to other subtypes of psoriasis. Of the 104 patients, 102 had GPP, including 88 von Zumbusch, 10 juvenile‐onset, and four annular pustular psoriasis. Although the male : female ratio of GPP with psoriasis vulgaris (GPP+PsV) (47/20) was similar to that of psoriasis in Japan, the GPP without PsV (GPP−PsV) group highlighted a female predominance (13/22). The mean age at GPP onset was 45.3 years, and the mean interval from PsV onset to GPP onset was 12.5 years. Four of nine patients with GPP had an IL36RN gene mutation. Infection, medicine, and pregnancy were the precipitating factors for GPP. A family history of psoriasis was present in eight (7.8%) patients with GPP. Twenty‐four patients with GPP had psoriatic arthritis. Biologics were used in 76.5% of patients with GPP, followed by etretinate (37.3%), cyclosporine (24.5%), methotrexate (13.7%), apremilast (8.8%), and granulocyte and monocyte adsorption apheresis (6.9%). Etretinate was used in 17 (51.5%) of 33 patients with GPP with less than 10‐year history. Thus, etretinate remains a good treatment option for GPP even in the era of biologics. Hypertension was the most commonly identified comorbidity, followed by diabetes. We believe that the characteristics revealed in this study can further contribute to effective GPP management.