A Method for Identifying Environmental Stimuli and Genes Responsible for Genotype-by-Environment Interactions From a Large-Scale Multi-Environment Data Set

It has not been fully understood in real fields what environment stimuli cause the genotype-by-environment (G × E) interactions, when they occur, and what genes react to them. Large-scale multi-environment data sets are attractive data sources for these purposes because they potentially experienced various environmental conditions. Here we developed a data-driven approach termed Environmental Covariate Search Affecting Genetic Correlations (ECGC) to identify environmental stimuli and genes responsible for the G × E interactions from large-scale multi-environment data sets. ECGC was applied to a soybean (Glycine max) data set that consisted of 25,158 records collected at 52 environments. ECGC illustrated what meteorological factors shaped the G × E interactions in six traits including yield, flowering time, and protein content and when these factors were involved in the interactions. For example, it illustrated the relevance of precipitation around sowing dates and hours of sunshine just before maturity to the interactions observed for yield. Moreover, genome-wide association mapping on the sensitivities to the identified stimuli discovered candidate and known genes responsible for the G × E interactions. Our results demonstrate the capability of data-driven approaches to bring novel insights on the G × E interactions observed in fields.

The Prepropalustrin-2CE2 and Preprobrevinin-2CE3 Gene from Rana Chensinensis: Gene Expression, Genomic Organization, and Functional Analysis of the Promoter Activity

Background: Palustrin-2CE2 and brevinin-2CE3 are antimicrobial peptides from Rana chensinensis. In R. chensinensis tadpoles, the expression of prepropalustrin-2CE2 and preprobrevinin-2CE3 increased with the developmental stage. In addition, the expression of the two genes was dramatically upregulated with stimulation by Escherichia coli, Staphylococcus aureus, and the chemical lipopolysaccharide (LPS). The genomic organization of the two antimicrobial peptide genes was confirmed. Both prepropalustrin-2CE2 and preprobrevinin-2CE3 contain three exons separated by two large introns. Additionally, several presumed transcription factor binding sites were identified in the promoter sequence. Functional analysis of the promoter was performed using a luciferase reporter system, and further confirmed by yeast one-hybrid experiment and EMSA assay. The results indicated that the transcription factors NF-κB and RelA are involved in regulating the expression of prepropalustrin-2CE2 and preprobrevinin-2CE3. As amphibian populations decline globally, this study provides new data demonstrating how frogs defend against pathogens from the environment by regulating AMP expression. For amphibians, antimicrobial peptides are innate immune molecules that resist adverse external environmental stimuli. However, the regulation mechanism of antimicrobial peptide gene expression in frogs is still unclear. Objective: The two antimicrobial peptides, palustrin-2CE2 and brevinin-2CE3, are produced under external stimulation in Rana chensinensis. Using this model, we analyzed the gene structure and regulatory elements of the two antimicrobial peptide genes and explored the regulatory effects of related transcription factors on the two genes. Method: Different stimuli such as E. coli, S. aureus, and chemical substance lipopolysaccharide (LPS) were applied to Rana chensinensis tadpoles at different developmental stages, and antimicrobial peptide expression levels were detected by RT-PCR. Bioinformatics analysis and 5'-RACE and genome walking technologies were employed to analyze the genome structure and promoter region of the antimicrobial peptide genes. With dual-luciferase reporter gene assays, yeast one-hybrid experiment and EMSA assays, we assessed the regulatory effect of the endogenous regulators of the cell on the antimicrobial peptide promoter. Results: The transcription levels of prepropalustrin-2CE2 and preprobrevinin-2CE3 were significantly upregulated after different stimulations. Genomic structure analysis showed that both genes contained three exons and two introns. Promoter analysis indicated that there are binding sites for regulatory factors of the NF-κB family in the promoter region, and experiments showed that endogenous NF-κB family regulatory factors in frog cells activate the promoters of the antimicrobial peptide genes. Yeast one-hybrid experiment and EMSA assay demonstrated that RelA and NF-κB1 might interact with specific motifs in the prepropalustrin-2CE2 promoter. Conclusion: In this paper, we found that the gene expression levels of the antimicrobial peptides, palustrin-2CE2 and brevinin-2CE3, in R. chensinensis will increase under environmental stimuli, and we verified that the changes in gene expression levels are affected by the transcription factors RelA and NF-κB1. The yeast one-hybrid experiment and EMSA assay confirmed that RelA and NF-κB1 could directly interact with the frog antimicrobial peptide gene promoter, providing new data for the regulatory mechanism of antimicrobial peptides in response to environmental stimuli.

A method for identifying environmental stimuli and genes responsible for genotype-by-environment interactions from a large-scale multi-environment data set

It has not been fully understood in real fields what environment stimuli cause the genotype-by-environment (G x E) interactions, when they occur, and what genes react to them. Large-scale multi-environment data sets are attractive data sources for these purposes because they potentially experienced various environmental conditions. Here we developed a data-driven approach termed Environmental Covariate Search Affecting Genetic Correlations (ECGC) to identify environmental stimuli and genes responsible for the G x E interactions from large-scale multi-environment data sets. ECGC was applied to a soybean (Glycine max) data set that consisted of 25,158 records collected at 52 environments. ECGC illustrated what meteorological factors shaped the G x E interactions in six traits including yield, flowering time, and protein content and when they were involved. For example, it illustrated the relevance of precipitation around sowing dates and hours of sunshine just before maturity to the interactions observed for yield. Moreover, genome-wide association mapping on the sensitivities to the identified stimuli discovered candidate and known genes responsible for the G x E interactions. Our results demonstrate the capability of data-driven approaches to bring novel insights on the G x E interactions observed in fields.

Fibroblast Memory in Development, Homeostasis and Disease

Fibroblasts are the major cell population in the connective tissue of most organs, where they are essential for their structural integrity. They are best known for their role in remodelling the extracellular matrix, however more recently they have been recognised as a functionally highly diverse cell population that constantly responds and adapts to their environment. Biological memory is the process of a sustained altered cellular state and functions in response to a transient or persistent environmental stimulus. While it is well established that fibroblasts retain a memory of their anatomical location, how other environmental stimuli influence fibroblast behaviour and function is less clear. The ability of fibroblasts to respond and memorise different environmental stimuli is essential for tissue development and homeostasis and may become dysregulated in chronic disease conditions such as fibrosis and cancer. Here we summarise the four emerging key areas of fibroblast adaptation: positional, mechanical, inflammatory, and metabolic memory and highlight the underlying mechanisms and their implications in tissue homeostasis and disease.

400 - Environmental stimuli in nursing homes during the COVID-19 pandemic: Lessons learned to improve the management of challenging behavior

Challenging behavior is common in nursing home residents, especially in those with dementia. Our previous study suggested that a decrease in environmental stimuli (i.e., events that take place around residents but are not specifically directed at them) in nursing homes due to restrictions during the COVID-19 pandemic, may affect residents differently. To improve future care, the experience of practitioners can be used to learn about the effects of environmental stimuli on challenging behavior in specific resident groups during the pandemic.From the perspective of practitioners, this study aimed to learn from successful initiatives and observed effects of decreased environmental stimuli on challenging behavior in residents during anti-pandemic measures.An online survey among 199 Dutch nursing home practitioners was conducted from November 2020 to January 2021. Practitioners were asked about alleged effects of diminished environmental stimuli in residents with different types of challenging behavior (i.e., psychotic, depressed, anxious, agitated, apathetic) and with mild vs. advanced or without dementia. Also, their opinion about strategies to limit environmental stimuli was explored.Residents with advanced dementia and those with psychotic and agitated behavior seemed to benefit from diminished environmental stimuli. In contrast, residents without dementia and those with depressive and apathetic behavior seemed to be negatively affected by decreased environmental stimuli. Practitioners indicated that they would like to preserve various strategies to limit environmental stimuli in the future such as reducing the use of corridors adjacent to residents’ rooms. Also, they planned to use adjustments and new initiatives regarding organized activities such as an increased use of small-scale and person-oriented activities. Opinions were divided on receiving visitors in the living room and on imposing visiting hours. In open-ended questions, other initiatives were mentioned that can be useful in nursing home care.Various strategies and initiatives in nursing homes during the pandemic seem promising to meet individual needs. While many residents may be negatively affected by restrictions during the pandemic, specific resident groups may benefit from a decrease in environmental stimuli. These findings underline the importance of a good balance between stimuli and rest in the nursing home, tailored to an individual resident.

Molecular basis for the R-type anion channel QUAC1 activity in guard cells

SUMMARYThe rapid (R)-type anion channel plays a central role in controlling stomatal closure in plant guard cells, thus regulating the exchange of water and photosynthetic gas (CO2) in response to environmental stimuli. The activity of the R- type anion channel is regulated by malate. However, the molecular basis of the R-type anion channel activity remains elusive. Here, we describe the first cryo-EM structure of the R-type anion channel QUAC1 at 3.5 Å resolution in the presence of malate. The structure reveals that the QUAC1 is a symmetrical dimer, forming a single electropositive T-shaped pore for passing anions across the membrane. The transmembrane and cytoplasmic domains are assembled into a twisted bi-layer architecture, with the associated dimeric interfaces nearly perpendicular. Our structural and functional analyses reveal that QUAC1 functions as an inward rectifying anion channel and suggests a mechanism for malate-mediated channel activation. Altogether, our study uncovers the molecular basis for a novel class of anion channels and provides insights into the gating and modulation of the R-type anion channel.

The Influence of Epigenetic Modifications on Metabolic Changes in White Adipose Tissue and Liver and Their Potential Impact in Exercise

Background: Epigenetic marks are responsive to a wide variety of environmental stimuli and serve as important mediators for gene transcription. A number of chromatin modifying enzymes orchestrate epigenetic responses to environmental stimuli, with a growing body of research examining how changes in metabolic substrates or co-factors alter epigenetic modifications.Scope of Review: Here, we provide a systematic review of existing evidence of metabolism-related epigenetic changes in white adipose tissue (WAT) and the liver and generate secondary hypotheses on how exercise may impact metabolism-related epigenetic marks in these tissues.Major Conclusions: Epigenetic changes contribute to the complex transcriptional responses associated with WAT lipolysis, hepatic de novo lipogenesis, and hepatic gluconeogenesis. While these metabolic responses may hypothetically be altered with acute and chronic exercise, direct testing is needed.

Co-creation of services: an online network perspective

PurposeIn the co-creation process from a network perspective, service is produced, designed, and evaluated entirely by the actors with dynamic roles and with less participation by the firm's employees in the service process. The purpose of this paper is to develop a theoretical model that represents environmental stimuli and value perceptions that contribute to service co-creation behaviour in an online network.Design/methodology/approachA total of 36 semi-structured interviews were conducted with members of two online programming communities – GitHub and Stack Overflow co-creators, with the data analysed using thematic analysis. The stimulus-organism-response model guided the development of the final model.FindingsSocial influence and trust are influential in actor value perceptions, including primary and network value, the interplay of which leads actors to co-production, supportive, and administrative behaviour. Environmental factors do not directly drive actors; rather it is the value that initiates and drives actors, which, by extension, initiates and drives the co-creation of services.Research limitations/implicationsThe service co-creation behaviour model provides a basis for future research in the co-creation and co-destruction context to model behaviours within the online network organisation setting and thereby enable improvement of such systems. This model can be operationalised in a network environment through design features.Originality/valueThis paper provides a rich understanding of environmental stimuli and value perception factors that contribute to the co-creation of services, and identifies different types of behaviours in dynamic online networks. This paper presents a new model of different types of behaviours emerging from actor participation in the co-creation process.