bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteogenomic integration reveals CXCL10 as a potentially downstream causal mediator for IL-6 signaling on atherosclerosis
Authors: Prapiadou Savvina , Živković Luka , Thorand Barbara , George Marc J. , van der Laan Sander W. , Malik Rainer , Herder Christian , Koenig Wolfgang , Ueland Thor , Kleveland Ola , Aukrust Pal , Gullestad Lars , Bernhagen Jürgen , Pasterkamp Gerard , Peters Annette , Hingorani Aroon D. , Rosand Jonathan , Dichgans Martin , Anderson Christopher D. , Georgakis Marios K.
Published: March 2023

Background

Genetic and experimental studies support a causal involvement of interleukin-6 (IL-6) signaling in atheroprogression. While trials targeting IL-6 signaling are underway, any benefits must be balanced against an impaired host immune response. Dissecting the mechanisms that mediate the effects of IL-6 signaling on atherosclerosis could offer insights about novel drug targets with more specific effects.

Methods

Leveraging data from 522,681 individuals, we constructed a genetic instrument of 26 variants in the gene encoding the IL-6 receptor (IL-6R) that proxied for pharmacological IL-6R inhibition. Using Mendelian randomization (MR), we assessed its effects on 3,281 plasma proteins quantified with an aptamer-based assay in the INTERVAL cohort (n=3,301). Using mediation MR, we explored proteomic mediators of the effects of genetically proxied IL-6 signaling on coronary artery disease (CAD), large artery atherosclerotic stroke (LAAS), and peripheral artery disease (PAD). For significant mediators, we tested associations of their circulating levels with incident cardiovascular events in a population-based study (n=1,704) and explored the histological, transcriptomic, and cellular phenotypes correlated with their expression levels in samples from human atherosclerotic lesions.

Results

We found significant effects of genetically proxied IL-6 signaling on 70 circulating proteins involved in cytokine production/regulation and immune cell recruitment/differentiation, which correlated with the proteomic effects of pharmacological IL-6R inhibition in a clinical trial. Among the 70 significant proteins, genetically proxied circulating levels of CXCL10 were associated with risk of CAD, LAAS, and PAD with up to 67% of the effects of genetically downregulated IL-6 signaling on these endpoints mediated by decreases in CXCL10. Higher midlife circulating CXCL10 levels were associated with a larger number of cardiovascular events over 20 years, whereas higherCXCL10expression in human atherosclerotic lesions correlated with a larger lipid core and a transcriptomic profile reflecting immune cell infiltration, adaptive immune system activation, and cytokine signaling.

Conclusions

Integrating multiomics data, we found a proteomic signature of IL-6 signaling activation and mediators of its effects on cardiovascular disease. Our analyses suggest the interferon-γ-inducible chemokine CXCL10 to be a potentially causal mediator for atherosclerosis in three vascular compartments and as such could serve as a promising drug target for atheroprotection.
exFINDER: identify external communication signals using single-cell transcriptomics data
Authors: He Changhan , Zhou Peijie , Nie Qing
Published: March 2023

Cells make decisions through their communication with other cells and receiving signals from their environment. Using single-cell transcriptomics, computational tools have been developed to infer cell-cell communication through ligands and receptors. However, the existing methods only deal with signals sent by the measured cells in the data, the received signals from the external system are missing in the inference. Here, we present exFINDER, a method that identifies such external signals received by the cells in the single-cell transcriptomics datasets by utilizing the prior knowledge of signaling pathways. In particular, exFINDER can uncover external signals that activate the given target genes, infer the external signal-target signaling network (exSigNet), and perform quantitative analysis on exSigNets. The applications of exFINDER to scRNA-seq datasets from different species demonstrate the accuracy and robustness of identifying external signals, revealing critical transition-related signaling activities, inferring critical external signals and targets, clustering signal-target paths, and evaluating relevant biological events. Overall, exFINDER can be applied to scRNA-seq data to reveal the external signal-associated activities and maybe novel cells that send such signals.
Deep Boosted Molecular Dynamics (DBMD): Accelerating molecular simulations with Gaussian boost potentials generated using probabilistic Bayesian deep neural network
Authors: Do Hung N. , Miao Yinglong
Published: March 2023

We have developed a new Deep Boosted Molecular Dynamics (DBMD) method. Probabilistic Bayesian neural network models were implemented to construct boost potentials that exhibit Gaussian distribution with minimized anharmonicity, thereby allowing for accurate energetic reweighting and enhanced sampling of molecular simulations. DBMD was demonstrated on model systems of alanine dipeptide and the fast-folding protein and RNA structures. For alanine dipeptide, 30ns DMBD simulations captured up to 83-125 times more backbone dihedral transitions than 1µs conventional molecular dynamics (cMD) simulations and were able to accurately reproduce the original free energy profiles. Moreover, DBMD sampled multiple folding and unfolding events within 300ns simulations of the chignolin model protein and identified low-energy conformational states comparable to previous simulation findings. Finally, DBMD captured a general folding pathway of three hairpin RNAs with the GCAA, GAAA, and UUCG tetraloops. Based on Deep Learning neural network, DBMD provides a powerful and generally applicable approach to boosting biomolecular simulations. DBMD is available with open source in OpenMM athttps://github.com/MiaoLab20/DBMD/.
IDSL.GOA: Gene Ontology Analysis for Interpreting Metabolomic datasets
Authors: Mahajan Priyanka , Fiehn Oliver , Barupal Dinesh
Published: March 2023

Biological interpretation of metabolomic datasets often ends at a pathway analysis step to find the over-represented metabolic pathways in the list of statistically significant metabolites. However, definitions of biochemical pathways and metabolite coverage vary among different curated databases, leading to missed interpretations. For the lists of genes, transcripts and proteins, Gene Ontology (GO) terms over-presentation analysis has become a standardized approach for biological interpretation. But, GO analysis has not been achieved for metabolomic datasets. We present a new knowledgebase (KB) and the online tool, Gene Ontology Analysis by the Integrated Data Science Laboratory for Metabolomics and Exposomics (IDSL.GOA) to conduct GO over-representation analysis for a metabolite list. The IDSL.GOA KB covers 2,393 metabolic GO terms and associated 3,144 genes, 1,492 EC annotations, and 2,621 metabolites. IDSL.GOA analysis of a case study of older vs young female brain cortex metabolome highlighted 82 GO terms being significantly overrepresented (FDR <0.05). We showed how IDSL.GOA identified key and relevant GO metabolic processes that were not yet covered in other pathway databases. Overall, we suggest that interpretation of metabolite lists should not be limited to only pathway maps and can also leverage GO terms as well. IDSL.GOA provides a useful tool for this purpose, allowing for a more comprehensive and accurate analysis of metabolite pathway data. IDSL.GOA tool can be accessed athttps://goa.idsl.me/
Lepidoptera proboscis pollens are mainly derived from nectar
Authors: Ma Baiwei , Chen Qi , Lin Fei , Wang Guirong , Ren Bingzhong
Published: March 2023

The pollens which are rejected or ignored by the dry stigma can’t germinate since they haven’t acquired sugar solution from dry stigmas. But almost all research has ignored the participation of insects which may transport pollens from the nectar to stigmas, and that pollens may germinate on the dry stigma since they have soaked in the nectar. So, the key question is that whether insects carry pollens from nectar to the stigma.

Since the adult Lepidoptera are important to the plant pollination and there is a general consensus that pollens are mainly deposited on the proboscis of adult Lepidoptera, and pollens are ubiquitous in the nectar of field flowers, we simulated the flower environment to conduct several groups of behavioral experiments in the adultMythimna separataby controlling the presence, absence or movement of pollens in nectar, then counted and compared the proboscis pollens.

We found that the pollens on the proboscis were mainly derived from the nectar.

Our conclusion may contributes to the research of pollen germination on stigmas, especially the dry stigma, and also shows the importance of adult Lepidoptera to pollination, even supports the coevolution of Lepidoptera and angiosperm.
Designer grass pea for transgene-free minimal neurotoxin-containing seeds with CRISPR-Cas9
Authors: Saha Tanushree , Shee Ranjana , Sahid Salman , Shee Dibyendu , Roy Chandan , Sharma Rajni , Pandey Ashutosh , Paul Soumitra , Datta Riddhi
Published: March 2023

Grass pea seeds are consumed as food in several South Asian and Sub-Saharan African nations. However, the presence of the neurotoxic compound N-oxalyl-L-diamino propionic acid (β-ODAP) has restricted its cultivation. Although various cultivars with low β-ODAP levels have been developed, their cultivation is still limited due to the risk of neurolathyrism from long-term grass pea seed ingestion. In this study, we employed the CRISPR-Cas9-mediated gene editing technique to generate grass pea seeds with zero or minimal β-ODAP levels. We targeted theBAHD-AT3gene that encodes a key enzyme in the β-ODAP biosynthesis pathway. We developedbahd-at3knock-out lines using three gRNAs targeting different regions of this gene and characterized them. Cas9-free independent lines from each event carrying the desired on-target mutation were selected and backcrossed twice with the wild-type to eliminate any off-target mutation present therein. Various agronomical parameters were analyzed from the backcrossed mutant lines and they displayed no phenotypic abnormalities. Interestingly, the seed β-ODAP content ranged between 0.001 % - 0.002 % of dry weight which is 99 % lower than the wild-type. Together, our study reports the development of transgene-free, genome-edited grass peas with insignificant levels of β-ODAP in seeds for safer food in the future.
Identification of two novel polygalacturonase-inhibiting proteins (PGIPs) and their genomic reorganization in chickpea (Cicer arietinum)
Authors: Ellur Vishnutej , Wei Wei , Ghogare Rishikesh , Solanki Shyam , Vandemark George , Brueggeman Robert , Chen Weidong
Published: March 2023

Polygalacturonase inhibiting proteins (PGIPs) are cell wall-anchored proteins that inhibit pathogen polygalacturonases (PGs). PGIPs, like other resistance genes, contain extracytoplasmic leucine-rich repeats (eLRRs), which are required for pathogen PG recognition. The importance of these PGIPs in plant defense has been well documented. This study focuses on chickpea (Cicer arietinum) PGIPs (CaPGIPs) owing to limited information available on this important crop. In this study, we identified and characterized two novelCapgips(Capgip3andCapgip4) in addition to the previously reportedCapgip1andCapgip2. Our analysis showed that CaPGIP1, CaPGIP3, and CaPGIP4 proteins contain N-terminal signal peptides, ten LRRs, theoretical molecular mass, and isoelectric points like other legume PGIPs. However, the previously reported CaPGIP2 cannot be classified as a true PGIP since it lacked a signal peptide, more than half of the LRRs, and other characteristics of a typical PGIP. Phylogenetic analysis and multiple sequence alignment revealed that theCapgipamino acid sequences are similar to the other reported legumes. Several cis-acting elements that are typical of pathogen response, tissue-specific activity, hormone response, and abiotic stress-related are present in the promoters ofCapgip1, Capgip3, andCapgip4. Localization experiments showed thatCapgip1, Capgip3, andCapgip4are located in the cell wall or membrane, whereasCapgip2is found in the endoplasmic reticulum.Capgiptranscript levels analyzed at normal conditions show constitutive tissue specific expression and heterozygous expression patterns analogous to other defense related gene families. All these findings suggest that CaPGIPs could have the potential to combat chickpea pathogens.
Within population plastic responses to combined thermal-nutritional stress differ from those in response to single stressors, and are genetically independent across traits in both males and females
Authors: Choy Yeuk Man Movis , Walter Greg M. , Mirth Christen K. , Sgrò Carla M.
Published: March 2023

Phenotypic plasticity helps animals to buffer the effects of increasing thermal and nutritional stress created by climate change. Plastic responses to single and combined stressors can vary among genetically diverged populations. However, less is known about how plasticity in response to combined stress varies among individuals within a population or whether such variation changes across life-history traits. This is important because individual variation within populations shapes population-level responses to environmental change. Here, we used isogenic lines ofDrosophila melanogasterto assess plasticity of egg-to-adult viability and sex-specific body size for combinations of two temperatures (25°C or 28°C) and three diets (standard diet, low caloric diet, or low protein:carbohydrate ratio diet). Our results reveal substantial within-population genetic variation in plasticity for egg-to-adult viability and wing size in response to combined thermal-nutritional stress. This genetic variation in plasticity was a result of cross-environment genetic correlations that were often < 1 for both traits, as well as changes in the expression of genetic variation across environments for egg-to-adult viability. Cross-sex genetic correlations for body size were weaker when the sexes were reared in different conditions, suggesting that the genetic basis of traits may change with the environment. Further, our results suggest that plasticity in egg-to-adult viability is genetically independent from plasticity in body size. Importantly, plasticity in response to diet and temperature individually differed from plastic shifts in response to diet and temperature in combination. By quantifying plasticity and the expression of genetic variance in response to combined stress across traits, our study reveals the complexity of animal responses to environmental change, and the need for a more nuanced understanding of the potential for populations to adapt to ongoing climate change.
Chromosomal Duplications of MurZ (MurA2) or MurA (MurA1), Amino Acid Substitutions in MurZ (MurA2), and Absence of KhpAB Obviate the Requirement for Protein Phosphorylation inStreptococcus pneumoniaeD39
Authors: Tsui Ho-Ching Tiffany , Joseph Merrin , Zheng Jiaqi J. , Perez Amilcar J. , Manzoor Irfan , Rued Britta E. , Richardson John D. , Branny Pavel , Doubravová Linda , Massidda Orietta , Winkler Malcolm E.
Published: March 2023

GpsB links peptidoglycan synthases to other proteins that determine the shape of the respiratory pathogenStreptococcus pneumoniae(pneumococcus;Spn) and other low-GC Gram-positive bacteria. GpsB is also required for phosphorylation of proteins by the essential StkP(Spn) Ser/Thr protein kinase. Here we report three classes of frequently arising chromosomal duplications (≈21-176 genes) containingmurZ(MurZ-family homolog of MurA) ormurAthat suppress ΔgpsBor ΔstkP. These duplications arose from three different repeated sequences and demonstrate the facility of pneumococcus to modulate gene dosage of numerous genes. Overproduction of MurZ or MurA alone or overexpression of MurZ caused by ΔkhpABmutations suppressed ΔgpsBor ΔstkPphenotypes to varying extents. ΔgpsBand ΔstkPwere also suppressed by MurZ amino-acid changes distant from the active site, including one in commonly studied laboratory strains, and by truncation or deletion of the homolog of IreB(ReoM). Unlike in other Gram-positive bacteria, MurZ is predominant to MurA in pneumococcal cells. However, ΔgpsBand ΔstkPwere not suppressed by ΔclpCP, which did not alter MurZ or MurA amounts. These results support a model in which regulation of MurZ and MurA activity, likely by IreB(Spn), is the only essential requirement for protein phosphorylation in exponentially growing D39 pneumococcal cells.
Inducing an oxidized redox-balance improves anti-tumor CD8+T cell function
Authors: Oh Ju Hee , Cederberg Rachel A. , Tanaka Erin , Bopp Luisa , Ser Terri , Niyyati Sara , Patterson Annette E. , Amanat Neeku , Dutra Jared , Ye Patricia , Clark Meredith , Ward-Hartstonge Kirsten , Archambault Anne-Sophie , Tsui Janice , Lange Philipp F. , Tsai Sue , Verchere C. Bruce , Park Yongjin , Fabri Mario , Bennewith Kevin L. , Geltink Ramon I. Klein
Published: March 2023

Cancer immunotherapy using antigen-specific CD8+T cells depends on long-lasting anti-tumor function of thein vitroexpanded T cells. T cell function is intricately linked to the activity of many metabolic pathways directly impacting the ability of CD8+T cells to kill tumor cells. Metabolic conditioningin vitrobetter prepares CD8+T cells forin vivosurvival, tumor infiltration and tumor clearance. The mechanism underlyingin vitrometabolic conditioning-induced augmentedin vivoT cell function remains poorly understood. Here we show that metabolic conditioning of CD8+effector T cells induces an oxidized cellular redox balance at least in part mediated by increased mitochondrial reactive oxygen species (ROS). This redox shift contributes to enhancedin vivopersistence and tumor clearance. In human tumour-infiltrating T cells, altering the redox balanceex-vivoreinvigorated pro-inflammatory cytokine production. Therefore, we believe that redox alterations present a targetable pathway to increase T cell-based anti-tumor immunotherapy efficacy.
Significant reduction in blackfly bites following implementation of Slash and Clear: An option to consider for onchocerciasis elimination in areas of persistent transmission
Authors: Domche André , Nana Djeunga Hugues C. , Nwane Philippe B. , Njitchouang Guy R. , Fesuh Betrand Nono , Njiokou Flobert , Jacob Benjamin , Pion Sébastien D. , Kamgno Joseph
Published: March 2023

Background

Although “Slash and Clear” has proven effective in reducing blackfly densities in low transmission foci, the impact of this strategy in high transmission settings with large rivers and important vector densities remains to be demonstrated.

Methods/Principal findings

A controlled before-and-after community-based intervention comprising two arms (Bayomen as control site and Biatsota as intervention site) was carried out in the Mbam Valley (Centre Region, Cameroon). In each arm, baseline blackfly densities were collected over one year using the human landing method. The intervention consisted of destroying the trailing vegetation where blackflies breed. Blackfly densities were collected post-intervention to assess the impact of the intervention. Before the intervention, a total of 36,273 and 29,041 blackflies were collected in Bayomen and Biatsota, respectively. After the intervention period, the total blackfly density in the intervention site decreased from 29,041 to 20,011 (31.1% reduction), while an increase of 2·7% was observed in the control site (from 36,273 to 37,248). The Poisson mixed regression model shows that the reduction was significantly greater in the intervention site than in the control site (p<0.0005).

Conclusions/Significance

This study showed that “Slash and Clear” approach is feasible and has a significant impact on vector densities in a high transmission setting. Further studies are needed to investigate the long-term impact of this vector control approach, and how this promising strategy can be scaled-up and sustained until elimination of onchocerciasis.

Author summary

River blindness persists in some foci in Cameroon despite more than two decades of ivermectin-based preventive chemotherapy. Mass drug administration (MDA) appears insufficient to interrupt onchocerciasis transmission in these hotspots, and should be complemented by vector control, the most promising alternative strategy to date. In 2018, the effectiveness of a new community-based vector control approach, known as slash and clear, was demonstrated. This strategy involves the removal of trailing vegetation at breeding sites, a primary attachment points for blackfly larvae. In this study, we show that this environment-friendly intervention is feasible and has a significant impact on blackfly densities in high transmission settings. This promising intervention can be combined with regular annual ivermectin-based preventive chemotherapy to accelerate onchocerciasis elimination.
Wat1/mLst8, a TOR complex protein regulates mitochondrial integrity and calcium ion homeostasis in fission yeastS. pombe
Authors: Anjum Simmi , Srivastava Swati , Panigrahi Lalita , Ansari Uzair Ahmad , Trivedi Arun Kumar , Ahmed Shakil
Published: March 2023

The mTOR complexes play a fundamental role in mitochondrial biogenesis and cellular homeostasis. Wat1, an ortholog of mammalian Lst8 is an important component of TOR complex and is essential for the regulation of downstream signaling. Earlier we reported the role of Wat1 in oxidative stress response. Here, we show that the inactivation ofwat1leads to respiratory defects and mitochondrial depolarization leading to decrease in ATP production. The confocal and electron microscopy inwat1Δ cells revealed the fragmented mitochondrial morphology implying its role in mitochondrial fission. Furthermore, we also showed its role in autophagy and the maintenance of calcium ion homeostasis. Additionally,tor2-287mutant cells also exhibit defects in mitochondrial integrity indicating the TORC1-dependent involvement of Wat1 in the maintenance of mitochondrial homeostasis. The interaction studies of Wat1 and Tor2 with Por1 and Mmm1 proteins revealed a cross-talk between mitochondria and endoplasmic reticulum through the Mitochondria-associated membranes (MAM) and endoplasmic reticulum-mitochondria encounter structure (ERMES) complex, involving TORC1. Taken together, this study demonstrates involvement of Wat1/mLst8 in harmonizing various mitochondrial functions, redox status, and Ca2+homeostasis.
Bacteriophage-mediated decolonization ofEnterobacteriaceaein a novelGalleria mellonellagut colonization model
Authors: Mirza Kamran A. , Jacob Sebastian , Nietzsche Sandor , Makarewicz Oliwia , Pletz Mathias W. , Thieme Lara
Published: March 2023

Purpose

Galleria mellonellalarvae have emerged as an invertebrate model for studying bacterial pathogenesis and novel therapeutic options due to ethical concerns associated with the use of mammalian models such as mice. The benefits of usingG. mellonellalarvae include a less complex microbiome in the gut, making it suitable for gut colonization studies. The intestinal colonization ofKlebsiella pneumoniae(Kp) andEscherichia coli(Ec), two of the most antibiotic-resistant bacteria on the World Health Organization’s (WHO) priority list, plays a key role in the spread of antibiotic resistance. Bacteriophage therapy is emerging as a promising alternative for antibiotic-resistant bacteria due to its ability to specifically target and infect bacterial hosts, making it suitable for gut decontamination. This study aimed to establish a novelEnterobacteriaceae G. mellonellalarvae gut colonization model and compare the efficacy of conventional antibiotic treatment with a one-time phage cocktail in decolonizing the gut.

Approach

Larvae were force-fed with different concentrations of bacterial doses ofK. pneumoniaeandE. coliat 0 h, 24 h, and 48 h, followed by survival monitoring at 24 h intervals. After 48 h and 120 h of the last force feed, the colony forming unit (CFU) count in the gut was evaluated. After successful colonization, larvae were one-time force-fed with either a 107PFU/larvae bacteriophage cocktail or with ciprofloxacin 4 mg/L or meropenem 2 mg/L. After 24 h post phage feeding, CFU counts were determined.

Main findings

Three bacterial doses of 106CFU/larvae led to a stable gut colonization in the larvae gut regardless of theK. pneumoniaeandE. colistrains. Bacteriophage force-feeding reduced bacterial colonization by 4 log10CFU/larvae whereas antibiotic treatment led to a 2 log10CFU/larvae reduction compared to the control. The novel alternativeG. mellonellamodel for gut colonization studies can be used for proof-of-concept studies, reducing or even obviating the number of follow-up experiments in vertebrate models.
Placental Cell Conditioned Media Modifies Hematopoietic Stem Cell Transcriptome In Vitro
Authors: Harris Sean M. , Su Anthony L. , Dou John F. , Loch-Caruso Rita , Elkin Elana R. , Jaber Sammy , Bakulski Kelly M.
Published: March 2023

Background

Hematopoietic stem cells are cells that differentiate into all blood cell types. Although the placenta secretes hormones, proteins and other factors important for maternal and fetal health, cross-talk between placental cells and hematopoietic stem cells is poorly understood. Moreover, toxicant impacts on placental-hematopoietic stem cell communication is understudied. The goals of this study were to determine if factors secreted from placental cells alter transcriptomic responses in hematopoietic stem cells and if monoethylhexyl phthalate (MEHP), the bioactive metabolite of the pollutant diethylhexyl phthalate, modifies these effects.

Methods

We used K-562 and BeWo cells asin vitromodels of hematopoietic stem cells and placental syncytiotrophoblasts, respectively. We treated K-562 cells with medium conditioned by incubation with BeWo cells, medium conditioned with BeWo cells treated with 10 μM MEHP for 24 hours, or controls treated with unconditioned medium. We extracted K-562 cell RNA, performed RNA sequencing, then conducted differential gene expression and pathway analysis by treatment group.

Results

Relative to controls, K-562 cells treated with BeWo cell conditioned medium differentially expressed 173 genes (FDR<0.05 and fold-change>2.0), including 2.4 fold upregulatation ofTPM4and 3.3 fold upregulatation ofS1PR3. Upregulated genes were enriched for pathways including stem cell maintenance, cell proliferation and immune processes. Downregulated genes were enriched for terms involved in protein translation and transcriptional regulation. MEHP treatment differentially expressed eight genes (FDR<0.05), including genes involved in lipid metabolism (PLIN2, fold-change: 1.4;CPT1A, fold-change: 1.4).

Conclusion

K-562 cells, a model of hematopoietic stem cells, are responsive to media conditioned by placental cells, potentially impacting pathways like stem cell maintenance and proliferation.
Enhanced niche colonisation and competition during bacterial adaptation to a fungus
Authors: Richter Anne , Blei Felix , Hu Guohai , Schwitalla Jan W. , Lozano-Andrade Carlos N. , Jarmusch Scott A , Wibowo Mario , Kjeldgaard Bodil , Surabhi Surabhi , Jautzus Theresa , Phippen Christopher B. W. , Tyc Olaf , Arentshorst Mark , Wang Yue , Garbeva Paolina , Larsen Thomas Ostenfeld , Ram Arthur F.J. , van den Hondel Cees A.M. , Maróti Gergely , Kovács Ákos T.
Published: March 2023

Bacterial-fungal interactions (BFIs) influence microbial community performance of most ecosystems and elicit specific microbial behaviours, including stimulating specialised metabolite production. Using a simple BFI system encompassing the Gram-positive bacteriumBacillus subtilisand the black mould fungusAspergillus niger, we established a co-culture experimental evolution method to investigate bacterial adaptation to the presence of a fungus. In the evolving populations,B. subtiliswas rapidly selected for enhanced production of the lipopeptide surfactin and accelerated surface spreading ability, leading to inhibition of fungal expansion and acidification of the environment. These phenotypes were explained by specific mutations in the DegS-DegU two-component system. In the presence of surfactin, fungal hyphae exhibited bulging cells with delocalised secretory vesicles and RlmA-dependent cell wall stress induction. Increased surfactin production typically enhances the competitive success of bacteria against fungi, which likely explains the primary adaption path in the presence ofA. niger.

Significance statement

Experimental evolution and co-cultivation of different microbes are important and useful techniques for discovering new traits and unravelling cryptic regulatory connections. We combined these methods by evolving the Gram-positive bacteriumBacillus subtilisin the presence of the black mould fungusAspergillus nigerthat were previously shown to engage in an intricate and physical interaction. Both are ubiquitous, environmentally and industrially relevant model microbes in the colonisation of rhizo- and endosphere and in the production of enzymes. Our results demonstrate how laboratory adaptation can be exploited to improve biocontrol properties of bacteria.
A head-to-head comparison of two DREADD agonists for suppressing operant behavior in rats via VTA dopamine neuron inhibition
Authors: Lawson Kate A , Ruiz Christina M , Mahler Stephen V
Published: March 2023

Rationale

Designer receptors exclusively activated by designer drugs (DREADDs) are a tool for “remote control” of defined neuronal populations during behavior. These receptors are inert unless bound by an experimenter-administered designer drug, most commonly clozapine-n-oxide (CNO). However, questions have emerged about the suitability of CNO as a systemically administered DREADD agonist.

Objectives

Second-generation agonists such as JHU37160 (J60) have been developed, which may have more favorable properties than CNO. Here we sought to directly compare effects of CNO (0, 1, 5, & 10 mg/kg, i.p.) and J60 (0, 0.03, 0.3, & 3 mg/kg, i.p.) on operant food pursuit.

Methods

Male and female TH:Cre+ rats and their wildtype (WT) littermates received cre-dependent hM4Di-mCherry vector injections into ventral tegmental area (VTA), causing inhibitory DREADD expression in VTA dopamine neurons in TH:Cre+ rats. Rats were trained to stably lever press for palatable food on a fixed ratio 10 schedule, and doses of both agonists were tested on separate days in a counterbalanced order.

Results

All three CNO doses reduced operant food seeking in rats with DREADDs, and no CNO dose had behavioral effects in WT controls. The highest tested J60 dose significantly reduced responding in DREADD rats, but this dose alsoincreasedresponding in WTs, indicating non-specific effects. The magnitude of CNO and J60 effects in TH:Cre+ rats were correlated and were present in both sexes.

Conclusions

Findings demonstrate the usefulness of directly comparing DREADD agonists when optimizing behavioral chemogenetics, and highlight the importance of proper controls, regardless of the DREADD agonist employed.
Evolution of an alternative genetic code in theProvidenciasymbiont of the haematophagous leechHaementeria acuecueyetzin
Authors: Manzano-Marín Alejandro , Kvist Sebastian , Oceguera-Figueroa Alejandro
Published: March 2023

Strict blood-feeding animals are confronted with a strong B vitamin deficiency. Blood-feeding leeches from the Glossiphoniidae family, similarly to haematophagous insects, have evolved specialised organs called bacteriomes to harbour symbiotic bacteria. Leeches of theHaementeriagenus have two pairs of globular bacteriomes attached to the oesophagus which house intracellular ’CandidatusProvidencia siddallii’ bacteria. Previous work analysing a draft genome of theProvidenciasymbiont of the Mexican leechHaementeria officinalisshowed that, in this species, the bacteria hold a reduced genome capable of synthesising B vitamins. In this work, we aimed to expand our knowledge on the diversity and evolution ofProvidenciasymbionts ofHaementeria. For this purpose, we sequenced the symbiont genomes of three selected leech species. We found that all genomes are highly syntenic and have kept a stable genetic repertoire, mirroring ancient insect endosymbionts. Additionally, we found B vitamin pathways to be conserved among these symbionts, pointing to a conserved symbiotic role. Lastly and most notably, we found that the symbiont ofHaementeria acuecueyetzinhas evolved an alternative genetic code, affecting a portion of its proteome and showing evidence of a lineage-specific and likely intermediate stage of genetic code reassignment.
Regulatory Variants on the Leukocyte Immunoglobulin-Like Receptor Gene Cluster are Associated with Crohn’s Disease and Interact with Regulatory Variants forTAP2
Authors: Kim Kwangwoo , Oh Shin Ju , Lee Junho , Kwon Ayeong , Yu Chae-Yeon , Kim Sangsoo , Choi Chang Hwan , Kang Sang-Bum , Kim Tae Oh , Park Dong Il , Lee Chang Kyun
Published: March 2023

Background and Aims

Crohn’s disease (CD) has a complex polygenic etiology with high heritability. We keep putting an effort to identify novel variants associated with susceptibility to CD through a genome-wide association study (GWAS) in large Korean populations.

Methods

Genome-wide variant data from 902 Korean patients with CD and 72,179 controls were used to assess the genetic associations in a meta-analysis with previous Korean GWAS results from 1,621 patients with CD and 4,419 controls. Epistatic interactions between CD-risk variants of interest were tested using a multivariate logistic regression model with an interaction term.

Results

We identified two novel genetic associations with the risk of CD nearZBTB38and within the leukocyte immunoglobulin-like receptor (LILR) gene cluster (P<5×10−8), with highly consistent effect sizes between the two independent Korean cohorts. CD-risk variants in the LILR locus are known quantitative trait loci (QTL) for multiple LILR genes, of whichLILRB2directly interacts with various ligands including MHC class I molecules. The LILR lead variant exhibited a significant epistatic interaction with CD-associated regulatory variants forTAP2involved in the antigen presentation of MHC class I molecules (P=4.11×10−4), showing higher CD-risk effects of theTAP2variant in individuals carrying more risk alleles of the LILR lead variant (OR=0.941,P=0.686 in non-carriers; OR=1.45,P=2.51×10−4in single-copy carriers; OR=2.38,P=2.76×10−6in two-copy carriers).

Conclusions

This study demonstrated that genetic variants at two novel susceptibility loci and the epistatic interaction between variants in LILR andTAP2loci confer risk of CD.
Strategies to deliver smoking cessation interventions during targeted lung health screening - a systematic review and meta-analysis
Authors: Williams Parris J , Philip Keir EJ , Alghamdi Saeed M , Perkins Alexis M , Buttery Sara C , Polkey Michael I , Laverty Anthony A , Hopkinson Nicholas S
Published: March 2023

Introduction

Lung cancer screening presents an important teachable moment to promote smoking cessation, but the most effective strategy to deliver support in this context remains to be established.

Methods

We undertook a systematic review and meta-analysis of smoking cessation interventions delivered during lung health screening, published prior to 20/07/2022 MEDLINE, PsychINFO, CENTRAL, EMBASE, CINAHL and Scopus databases. Two reviewers screened titles, and abstracts, four reviewed each full text using prespecified criteria, extracted relevant data, assessed risk of bias and confidence in findings using the GRADE criteria. The review was registered prospectively on PROSPERO (CRD42021242431).

Results

10 randomised controlled trials (RCT) and 3 observational studies with a control group were identified. Meta-analysis of 9 RCTs demonstrated that smoking cessation interventions delivered during lung screening programmes increased quit rates compared to usual care (OR: 2.01, 95%: 1.49-2.72 p<0.001). 6 RCTs using intensive (≥3 behavioural counselling sessions) interventions demonstrated greater quit rates compared to usual care (OR: 2.11, 95% CI 1.53-2.90, p<0.001). A meta-analysis of 2 RCTs found intensive interventions were more effective than non-intensive (OR: 2.07, 95%CI 1.26-3.40 p=0.004), Meta-analysis of 2 RCTs of non-intensive interventions (≤2 behavioural counselling sessions or limited to online information audio take home materials such as pamphlets) did not show a higher quit rate than usual care (OR: 0.90, 95% CI 0.39-2.08 p=0.80).

Discussion

Moderate quality evidence supports smoking cessation interventions delivered within a lung screening setting compared to usual care, with high-quality evidence that more intensive interventions are likely to be most effective.
Understanding social media users' information avoidance intention: a C-A-C perspective
Authors: Zhou Tao , Xie Yingying
Published: March 2023

Purpose

Based on the C-A-C framework, this article examined users' information avoidance intention in social media platforms.

Design/methodology/approach

The authors conducted data analysis using a mixed method of the SEM and fsQCA.

Findings

The results indicated that information overload, functional overload and social overload influence fatigue and dissatisfaction, both of which further determine users' information avoidance intention. The results of the fsQCA identified two paths that trigger users' information avoidance intention.

Originality/value

Extant studies have examined the information avoidance in the contexts of healthcare, academics and e-commerce, but have seldom explored the mechanism underlying users' information avoidance in social media. To fill this gap, this article will empirically investigate users' information avoidance in social media platforms based on the C-A-C framework.
Need to cut or freeze pay of your employees? Providing work–life balancing practices can help if maintaining employee morale is a concern
Authors: Yoon Yeongjoon , Sengupta Sukanya
Published: March 2023

Purpose

Research on the effect of pay cuts/freezes on employee morale is limited. More importantly, past studies examining this relationship tend to focus on fairness perception as a mediator. This study hypothesizes that work–life conflict also mediates the negative relationship between pay cuts/freezes and employee morale.

Design/methodology/approach

A total of 13,139 employees in 1,830 workplaces in Britain in the 2011 Workplace Employment Relations Survey were analyzed.

Findings

The analyses confirm the above hypothesis. The results also demonstrate that this mediating mechanism can be mitigated to some extent when work–life balancing practices are available, but much more strongly when they are actually used.

Practical implications

If possible, organizations should provide and encourage employees to use work–life balancing practices when employees' pay needs to be cut or frozen if maintaining employee morale is a concern.

Originality/value

Our study highlights the need to incorporate various theoretical frameworks, and not just the dominant justice/fairness theories, into the study of pay cuts and freezes. The current research demonstrates that the work–life conflict framework can also be applied to understand the relationship between pay cuts/freezes and employee morale.
Sustainable refurbishment of existing, typical single-family residential buildings in Greece
Authors: Bougiatioti Flora , Alexandrou Eleni , Katsaros Miltiadis
Published: March 2023

Purpose

Residential buildings in Greece constitute an important portion of the existing building stock. Furthermore, most of these buildings were built prior to the first Thermal Insulation Code of 1981. The article focuses on existing, typical residences built after 1920, which are found mostly in suburban areas and settlements all around Greece. The purpose of the research is to evaluate the effect of simple bioclimatic interventions focused on the improvement of their diurnal, inter-seasonal and annual thermal performance.

Design/methodology/approach

The applied strategies include application of thermal insulation in the building shell and openings, passive solar systems for the heating period and shading and natural ventilation for the summer period. The effect of the strategies is analysed with the use of building energy analysis. The simulation method was selected because it provides the possibility of parametric analysis and comparisons for different proposals in different orientations.

Findings

The results show that the increased thermal mass of the construction is the most decisive parameter of the thermal behaviour throughout the year.

Research limitations/implications

The typical residences under investigation are often found in urban and/or suburban surroundings. These mostly refer to free-standing buildings situated, which, in many cases, do not have the disadvantages and limitations that the geometrical characteristics of densely built urban locations impose on incident solar radiation (e.g. overshadowing during the winter) and air circulation (e.g. reduce natural ventilation during the summer). Nevertheless, even in these cases, the surrounding built environment may also have relevant negative effects, which were not taken under consideration and could be included in further, future research that will include the effect of various orientations, as well as of neighbouring buildings.

Practical implications

Existing residences built prior to the first Thermal Insulation Code (1981) form an important part of the building stock. Consequently their energy upgrade could contribute to significant conventional energy savings for heating and cooling, along with the inter-seasonal improvement of interior thermal comfort conditions.

Social implications

The proposed interventions can improve thermal comfort conditions and lead to a reduction of energy consumption for heating and cooling, which is an important step against energy poverty and the on-going energy crisis.

Originality/value

The proposed interventions only involve the building envelope and are simple with relatively low cost.
Adoption of additive manufacturing technology: drivers, barriers and impacts on upstream supply chain design
Authors: Ronchini Alessio , Moretto Antonella Maria , Caniato Federico
Published: March 2023

Purpose

This paper investigates how the adoption of additive manufacturing (AM) impacts upstream supply chain (SC) design and considers the influence of drivers and barriers towards the adoption.

Design/methodology/approach

Ten case studies investigating AM adoption by Original Equipment Manufacturers (OEMs) in five industries were conducted. This research is driven by a literature-based framework, and the results are discussed according to the theory of transaction cost economics (TCE).

Findings

The case studies reveal four patterns of AM adoption that affect upstream SC design (due to changes in supply base or types of buyer–supplier relationships): make, buy, make and buy and vertical integration. A make or buy decision is based on the level of experience with the technology, on the AM application (rapid manufacturing, prototyping or tooling) and on the need of control over production. Other barriers playing a role in the decision are the high initial investments and the lack of skills and knowledge.

Originality/value

This paper shows how different decisions regarding AM adoption result in different SC designs, with a specific focus on the upstream SC and changes in the supply base. This research is among the first to provide empirical evidence on the impact of AM adoption on upstream SCs and to identify drivers of the make or buy decision when adopting AM through the theoretical lens of TCE.
Temperature patterns obtained in thermoelastic stress test at different frequencies, a FEM approach
Authors: Duarte Guilherme , Neves Ana M.A. , Ramos Silva António
Published: March 2023

Purpose

The goal of this work is to create a computational finite element model to perform thermoelastic stress analysis (TSA) with the usage of a non-ideal load frequency, containing the effects of the material thermal properties.

Design/methodology/approach

Throughout this document, the methodology of the model is presented first, followed by the procedure and results. The last part is reserved to results, discussion and conclusions.

Findings

This work had the main goal to create a model to perform TSA with the usage of non-ideal loading frequencies, considering the materials’ thermal properties. Loading frequencies out of the ideal range were applied and the model showed capable of good results. The created model reproduced acceptably the TSA, with the desired conditions.

Originality/value

This work creates a model to perform TSA with the usage of non-ideal loading frequencies, considering the materials’ thermal properties.
Exploring the relationship between digitalization, resilient agri-food supply chain management practices and firm performance
Authors: Yadav Sanjeev , Luthra Sunil , Kumar Anil , Agrawal Rohit , Frederico Guilherme F.
Published: March 2023

Purpose

This study aims to explore the mediating role of digital technologies-based supply chain integrating (SCI) strategies on the agri-supply chain performance (SCP) and firm performance (FP). This research has introduced recently emerged digital technologies such as Internet of Things (IoT). Further, based on theoretical support and an extensive literature review, this research has proposed some hypotheses, which have been quantitatively validated for their significance.

Design/methodology/approach

A conceptual model was formulated based on an extensive literature review. Data for this research were gathered from a survey completed by 119 respondents from different departments of agri-firms. Further, partial least square (PLS)-based structured equation modelling (SEM) was used to test the proposed hypothetical model.

Findings

The results confirm that IoT-based digital technologies and supply chain processes (organization integration [OI], information sharing and customer integration [CI]) have a significant positive correlation. Furthermore, supply chain practices are positively associated with SCP. Finally, it has been found that FP is positively impacted by SCP.

Research limitations/implications

This research is used to analyse the mediating impacts of digital supply chain processes as a linking strategy for SCP and FP. For practical purposes, this research provides investment decisions for implementing digital technologies in SC strategies. The findings have proposed implications for managers and practitioners in agri-firms based on existing theories: contingency theory (CT) and relational view theory. Also, this study suggests the deployment of smarter electronically based tags and readers, which improve the data analytics capabilities based on auto-captured data. Thus, the availability of quality information improves the data-driven decisional capabilities of managers at company level.

Originality/value

This is a unique and original study exploring the relationship between digitalization, resilient agri-food supply chain (AFSC) management practices and firm performance. This research may be extended to other industries in view of the results from SCP and impact of digitalization.