Systems Biology
A training pipeline of an arrhythmia classifier for atrial fibrillation detection using Photoplethysmography signal
Front Physiol. 2023 Jan 19;14:1084837. doi: 10.3389/fphys.2023.1084837. eCollection 2023.
ABSTRACT
Photoplethysmography (PPG) signal is potentially suitable in atrial fibrillation (AF) detection for its convenience in use and similarity in physiological origin to electrocardiogram (ECG). There are a few preceding studies that have shown the possibility of using the peak-to-peak interval of the PPG signal (PPIp) in AF detection. However, as a generalized model, the accuracy of an AF detector should be pursued on the one hand; on the other hand, its generalizability should be paid attention to in view of the individual differences in PPG manifestation of even the same arrhythmia and the existence of sub-types. Moreover, a binary classifier for atrial fibrillation and normal sinus rhythm is not convincing enough for the similarity between AF and ectopic beats. In this study, we project the atrial fibrillation detection as a multiple-class classification and try to propose a training pipeline that is advantageous both to the accuracy and generalizability of the classifier by designing and determining the configurable options of the pipeline, in terms of input format, deep learning model (with hyperparameter optimization), and scheme of transfer learning. With a rigorous comparison of the possible combinations of the configurable components in the pipeline, we confirmed that first-order difference of heartbeat sequence as the input format, a 2-layer CNN-1-layer Transformer hybridR model as the learning model and the whole model fine-tuning as the implementing scheme of transfer learning is the best combination for the pipeline (F1 value: 0.80, overall accuracy: 0.87)R.
PMID:36744032 | PMC:PMC9892629 | DOI:10.3389/fphys.2023.1084837
Editorial: Ca<sup>2+</sup> signalling in plant biotic interactions
Front Plant Sci. 2023 Jan 20;14:1137001. doi: 10.3389/fpls.2023.1137001. eCollection 2023.
NO ABSTRACT
PMID:36743485 | PMC:PMC9895960 | DOI:10.3389/fpls.2023.1137001
Antioxidant Green Factories: Toward Sustainable Production of Vitamin E in Plant <em>In Vitro</em> Cultures
ACS Omega. 2023 Jan 13;8(4):3586-3605. doi: 10.1021/acsomega.2c05819. eCollection 2023 Jan 31.
ABSTRACT
Vitamin E is a dietary supplement synthesized only by photosynthetic organisms and, hence, is an essential vitamin for human well-being. Because of the ever-increasing demand for natural vitamin E and limitations in existing synthesis modes, attempts to improve its yield using plant in vitro cultures have gained traction in recent years. With inflating industrial production costs, integrative approaches to conventional bioprocess optimization is the need of the hour for multifold vitamin E productivity enhancement. In this review, we briefly discuss the structure, isomers, and important metabolic routes of biosynthesis for vitamin E in plants. We then emphasize its vital role in human health and its industrial applications and highlight the market demand and supply. We illustrate the advantages of in vitro plant cell/tissue culture cultivation as an alternative to current commercial production platforms for natural vitamin E. We touch upon the conventional vitamin E metabolic pathway engineering strategies, such as single/multigene overexpression and chloroplast engineering. We highlight the recent progress in plant systems biology to rationally identify metabolic bottlenecks and knockout targets in the vitamin E biosynthetic pathway. We then discuss bioprocess optimization strategies for sustainable vitamin E production, including media/process optimization, precursor/elicitor addition, and scale-up to bioreactors. We culminate the review with a short discussion on kinetic modeling to predict vitamin E production in plant cell cultures and suggestions on sustainable green extraction methods of vitamin E for reduced environmental impact. This review will be of interest to a wider research fraternity, including those from industry and academia working in the field of plant cell biology, plant biotechnology, and bioprocess engineering for phytochemical enhancement.
PMID:36743063 | PMC:PMC9893489 | DOI:10.1021/acsomega.2c05819
Systems Biology in ELIXIR: modelling in the spotlight
F1000Res. 2022 Nov 7;11:ELIXIR-1265. doi: 10.12688/f1000research.126734.1. eCollection 2022.
ABSTRACT
In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR's future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.
PMID:36742342 | PMC:PMC9871403 | DOI:10.12688/f1000research.126734.1
Reimagine fire science for the anthropocene
PNAS Nexus. 2022 Aug 4;1(3):pgac115. doi: 10.1093/pnasnexus/pgac115. eCollection 2022 Jul.
ABSTRACT
Fire is an integral component of ecosystems globally and a tool that humans have harnessed for millennia. Altered fire regimes are a fundamental cause and consequence of global change, impacting people and the biophysical systems on which they depend. As part of the newly emerging Anthropocene, marked by human-caused climate change and radical changes to ecosystems, fire danger is increasing, and fires are having increasingly devastating impacts on human health, infrastructure, and ecosystem services. Increasing fire danger is a vexing problem that requires deep transdisciplinary, trans-sector, and inclusive partnerships to address. Here, we outline barriers and opportunities in the next generation of fire science and provide guidance for investment in future research. We synthesize insights needed to better address the long-standing challenges of innovation across disciplines to (i) promote coordinated research efforts; (ii) embrace different ways of knowing and knowledge generation; (iii) promote exploration of fundamental science; (iv) capitalize on the "firehose" of data for societal benefit; and (v) integrate human and natural systems into models across multiple scales. Fire science is thus at a critical transitional moment. We need to shift from observation and modeled representations of varying components of climate, people, vegetation, and fire to more integrative and predictive approaches that support pathways toward mitigating and adapting to our increasingly flammable world, including the utilization of fire for human safety and benefit. Only through overcoming institutional silos and accessing knowledge across diverse communities can we effectively undertake research that improves outcomes in our more fiery future.
PMID:36741468 | PMC:PMC9896919 | DOI:10.1093/pnasnexus/pgac115
Crop genetic diversity uncovers metabolites, elements, and gene networks predicted to be associated with high plant biomass yields in maize
PNAS Nexus. 2022 Jul 4;1(3):pgac068. doi: 10.1093/pnasnexus/pgac068. eCollection 2022 Jul.
ABSTRACT
Rapid population growth and increasing demand for food, feed, and bioenergy in these times of unprecedented climate change require breeding for increased biomass production on the world's croplands. To accelerate breeding programs, knowledge of the relationship between biomass features and underlying gene networks is needed to guide future breeding efforts. To this end, large-scale multiomics datasets were created with genetically diverse maize lines, all grown in long-term organic and conventional cropping systems. Analysis of the datasets, integrated using regression modeling and network analysis revealed key metabolites, elements, gene transcripts, and gene networks, whose contents during vegetative growth substantially influence the build-up of plant biomass in the reproductive phase. We found that S and P content in the source leaf and P content in the root during the vegetative stage contributed the most to predicting plant performance at the reproductive stage. In agreement with the Gene Ontology enrichment analysis, the cis-motifs and identified transcription factors associated with upregulated genes under phosphate deficiency showed great diversity in the molecular response to phosphate deficiency in selected lines. Furthermore, our data demonstrate that genotype-dependent uptake, assimilation, and allocation of essential nutrient elements (especially C and N) during vegetative growth under phosphate starvation plays an important role in determining plant biomass by controlling root traits related to nutrient uptake. These integrative multiomics results revealed key factors underlying maize productivity and open new opportunities for efficient, rapid, and cost-effective plant breeding to increase biomass yield of the cereal crop maize under adverse environmental factors.
PMID:36741443 | PMC:PMC9896949 | DOI:10.1093/pnasnexus/pgac068
Deep-learning microscopy image reconstruction with quality control reveals second-scale rearrangements in RNA polymerase II clusters
PNAS Nexus. 2022 May 23;1(3):pgac065. doi: 10.1093/pnasnexus/pgac065. eCollection 2022 Jul.
ABSTRACT
Fluorescence microscopy, a central tool of biological research, is subject to inherent trade-offs in experiment design. For instance, image acquisition speed can only be increased in exchange for a lowered signal quality, or for an increased rate of photo-damage to the specimen. Computational denoising can recover some loss of signal, extending the trade-off margin for high-speed imaging. Recently proposed denoising on the basis of neural networks shows exceptional performance but raises concerns of errors typical of neural networks. Here, we present a work-flow that supports an empirically optimized reduction of exposure times, as well as per-image quality control to exclude images with reconstruction errors. We implement this work-flow on the basis of the denoising tool Noise2Void and assess the molecular state and 3D shape of RNA polymerase II (Pol II) clusters in live zebrafish embryos. Image acquisition speed could be tripled, achieving 2-s time resolution and 350-nm lateral image resolution. The obtained data reveal stereotyped events of approximately 10 s duration: initially, the molecular mark for recruited Pol II increases, then the mark for active Pol II increases, and finally Pol II clusters take on a stretched and unfolded shape. An independent analysis based on fixed sample images reproduces this sequence of events, and suggests that they are related to the transient association of genes with Pol II clusters. Our work-flow consists of procedures that can be implemented on commercial fluorescence microscopes without any hardware or software modification, and should, therefore, be transferable to many other applications.
PMID:36741438 | PMC:PMC9896941 | DOI:10.1093/pnasnexus/pgac065
PlantACT! - how to tackle the climate crisis
Trends Plant Sci. 2023 Feb 3:S1360-1385(23)00024-9. doi: 10.1016/j.tplants.2023.01.005. Online ahead of print.
ABSTRACT
Greenhouse gas (GHG) emissions have created a global climate crisis which requires immediate interventions to mitigate the negative effects on all aspects of life on this planet. As current agriculture and land use contributes up to 25% of total GHG emissions, plant scientists take center stage in finding possible solutions for a transition to sustainable agriculture and land use. In this article, the PlantACT! (Plants for climate ACTion!) initiative of plant scientists lays out a road map of how and in which areas plant scientists can contribute to finding immediate, mid-term, and long-term solutions, and what changes are necessary to implement these solutions at the personal, institutional, and funding levels.
PMID:36740490 | DOI:10.1016/j.tplants.2023.01.005
Dry tobacco leaves: an in vivo and in silico approach to the consequences of occupational exposure
Mutagenesis. 2023 Feb 4:gead003. doi: 10.1093/mutage/gead003. Online ahead of print.
ABSTRACT
Exposure of tobacco workers handling dried tobacco leaves has been linked to an increased risk of toxicity and respiratory illness due to the presence of nicotine and other chemicals. This study aimed to evaluate the DNA damage caused by the exposure of tobacco growers during the dry leaf classification process and the relation to cellular mechanisms. A total of 86 individuals participated in the study, divided into a group exposed to dry tobacco (n = 44) and a control group (n = 42). Genotoxicity was evaluated using the alkaline comet assay and lymphocyte micronucleus (MN) assay (CBMN-Cyt), and measurement of telomere length. The levels of oxidative and nitrosative stress were evaluated through the formation of thiobarbituric acid reactive species, and nitric oxide levels, respectively. The inorganic elements were measured in the samples using particle-induced X-ray emission method. The combination of variables was demonstrated through principal component analysis and the interactions were expanded through systems biology. Comet assay, MN, death cells, thiobarbituric acid reactive species, and nitrosative stress showed a significant increase for all exposed groups in relation to the control. Telomere length showed a significant decrease for exposed women and total exposed group in relation to men and control groups, respectively. Bromine (Br) and rubidium (Rb) in the exposed group presented higher levels than control groups. Correlations between nitrate and apoptosis; Br and MN and necrosis; and Rb and telomeres; besides age and DNA damage and death cells were observed. The systems biology analysis demonstrated that tobacco elements can increase the nuclear translocation of NFKB dimers inducing HDAC2 expression, which, associated with BRCA1 protein, can potentially repress transcription of genes that promote DNA repair. Dry tobacco workers exposed to dry leaves and their different agents showed DNA damage by different mechanisms, including redox imbalance.
PMID:36738258 | DOI:10.1093/mutage/gead003
Integrative pathway and network analysis provide insights on flooding-tolerance genes in soybean
Sci Rep. 2023 Feb 3;13(1):1980. doi: 10.1038/s41598-023-28593-1.
ABSTRACT
Soybean is highly sensitive to flooding and extreme rainfall. The phenotypic variation of flooding tolerance is a complex quantitative trait controlled by many genes and their interaction with environmental factors. We previously constructed a gene-pool relevant to soybean flooding-tolerant responses from integrated multiple omics and non-omics databases, and selected 144 prioritized flooding tolerance genes (FTgenes). In this study, we proposed a comprehensive framework at the systems level, using competitive (hypergeometric test) and self-contained (sum-statistic, sum-square-statistic) pathway-based approaches to identify biologically enriched pathways through evaluating the joint effects of the FTgenes within annotated pathways. These FTgenes were significantly enriched in 36 pathways in the Gene Ontology database. These pathways were related to plant hormones, defense-related, primary metabolic process, and system development pathways, which plays key roles in soybean flooding-induced responses. We further identified nine key FTgenes from important subnetworks extracted from several gene networks of enriched pathways. The nine key FTgenes were significantly expressed in soybean root under flooding stress in a qRT-PCR analysis. We demonstrated that this systems biology framework is promising to uncover important key genes underlying the molecular mechanisms of flooding-tolerant responses in soybean. This result supplied a good foundation for gene function analysis in further work.
PMID:36737640 | DOI:10.1038/s41598-023-28593-1
Enzyme expression kinetics by Escherichia coli during transition from rich to minimal media depends on proteome reserves
Nat Microbiol. 2023 Feb;8(2):347-359. doi: 10.1038/s41564-022-01310-w. Epub 2023 Feb 3.
ABSTRACT
Bacterial fitness depends on adaptability to changing environments. In rich growth medium, which is replete with amino acids, Escherichia coli primarily expresses protein synthesis machineries, which comprise ~40% of cellular proteins and are required for rapid growth. Upon transition to minimal medium, which lacks amino acids, biosynthetic enzymes are synthesized, eventually reaching ~15% of cellular proteins when growth fully resumes. We applied quantitative proteomics to analyse the timing of enzyme expression during such transitions, and established a simple positive relation between the onset time of enzyme synthesis and the fractional enzyme 'reserve' maintained by E. coli while growing in rich media. We devised and validated a coarse-grained kinetic model that quantitatively captures the enzyme recovery kinetics in different pathways, solely on the basis of proteomes immediately preceding the transition and well after its completion. Our model enables us to infer regulatory strategies underlying the 'as-needed' gene expression programme adopted by E. coli.
PMID:36737588 | DOI:10.1038/s41564-022-01310-w
Association of a third vaccination with antibody levels and side reactions in essential workers: A prospective cohort study
Vaccine. 2023 Feb 1:S0264-410X(23)00082-8. doi: 10.1016/j.vaccine.2023.01.050. Online ahead of print.
ABSTRACT
OBJECTIVE: To evaluate the relationship between the change of titer and adverse events after the third vaccination for COVID-19 among healthcare workers.
DESIGN AND SETTING: This was a prospective cohort study, and the follow-up period was from December 2021 to November 2023.
PARTICIPANTS: A total of 392 healthcare workers aged over 20 years who worked at the facility and wished to have vaccine antibody titers measured participated in this study.
EXPOSURES: A third dose of BNT162b2 COVID-19 vaccine was administered to healthcare workers working at the hospital, and we evaluated the changes in antibody titers before and after the vaccine, as well as adverse reactions after vaccination.
MAIN OUTCOMES AND MEASURES: The primary endpoints were adverse reactions within 7 days after the third dose of COVID-19 vaccine and the rate of increase in COVID-19 vaccine antibody titer at 4 weeks.
RESULTS: A total of 392 people participated in the study, of whom 358 participants had their antibody titers measured before and after the booster vaccination. The overall IgG geometric mean was 609 U/mL (561-663) before booster vaccination and increased to 18,735 U/mL (17,509-20,049) at 4 weeks after vaccination (p < 0.001). Multivariate analysis showed no statistically significant relationship between the primary endpoints, such as a change in antibody titer due to the presence of fever after vaccination or a change in antibody titer due to swelling at the vaccination site. Factors affecting the rate of increase in antibody titer, evaluated as secondary endpoints, were suggested to be age (1.02 (95 % confidence interval (CI): 1.01-1.03)) and hypertension (0.66 (95 % CI: 0.47-0.93)).
CONCLUSIONS AND RELEVANCE: In relation to the booster effect of the third dose of COVID-19 vaccination, there was no statistically significant difference in the presence of fever or use of antipyretic or other drugs.
PMID:36737319 | DOI:10.1016/j.vaccine.2023.01.050
Neutrophil extracellular trap-associated carbamylation and histones trigger osteoclast formation in rheumatoid arthritis
Ann Rheum Dis. 2023 Feb 3:ard-2022-223568. doi: 10.1136/ard-2022-223568. Online ahead of print.
ABSTRACT
OBJECTIVE: Neutrophil infiltration into the synovial joint is a hallmark of rheumatoid arthritis (RA), a disease characterised by progressive bone erosion. However, the mechanisms by which neutrophils participate in bone destruction remain unclear. Carbamylation is a posttranslational modification linked to increased bone erosion in RA and we previously showed that carbamylation is present in RA neutrophil extracellular traps (NETs). However, it remains unclear whether NETs and their carbamylated protein cargo directly promote bone destruction and alter osteoclast biology.
METHODS: NETs and carbamylated NETs (cNETs) were assessed for their capacity to induce osteoclast formation in CD14+ monocytes. Chemical inhibitors and neutralising antibodies were used to elucidate the pathway by which NETs induce osteoclastogenesis. HLA-DRB1*04:01 mice received intra-articular injection of cNETs for 4 weeks. Joints were isolated and assessed for osteoclast formation. Plasma and synovial fluid samples from patients with RA (n=32) were assessed for the presence of carbamylated histone, and correlations to disease specific outcomes were performed.
RESULTS: We found that NETs, when cNETs, instruct monocytes to undergo rapid osteoclast formation. NET-mediated osteoclastogenesis appears to depend on Toll-like receptor 4 signalling and NET-associated proteins including histones and neutrophil elastase. In vivo, we identified that the number of osteoclasts increased following immunisation with cNETs in HLA-DRB1*04:01 transgenic mice. Furthermore, carbamylated histones are increased in plasma and synovial fluid from patients with RA and correlate with active bone resorption and inflammatory markers.
CONCLUSIONS: Our results suggest that NETs have a direct role in RA-associated bone erosion by promoting osteoclast formation.
PMID:36737106 | DOI:10.1136/ard-2022-223568
Systems biology approach to understand the interplay between Bacillus anthracis and human host genes that leads to CVDs
Microb Pathog. 2023 Feb 1:106019. doi: 10.1016/j.micpath.2023.106019. Online ahead of print.
ABSTRACT
Humans infected with invasive Bacillus anthracis (B. anthracis) have a very poor prognosis and are at high risk for developing cardiovascular diseases (CVDs) and shock. Several bacterial elements probably have significant pathogenic roles in this pathogenic process of anthrax. In our current work, we have analysed the molecular level interactions between B. anthracis and human genes to understand the interplay during anthrax that leads to the CVDs. Our results have shown dense interactions between the functional partners in both host and the B. anthracis Gene interaction network (GIN). The functional enrichment analysis indicated that the clusters in the host GIN had genes related to hypoxia and autophagy in response to the lethal toxin; and genes related to adherens junction and actin cytoskeleton in response to edema toxin play a significant role in multiple stages of the disease. The B. anthracis genes BA_0530, guaA, polA, rpoB, ribD, secDF, metS, dinG and human genes ACTB, EGFR, EP300, CTNNB1, ESR1 have shown more than 50 direct interactions with the functional partners and hence they can be considered as hub genes in the network and they are observed to have important roles in CVDs. The outcome of our study will help to understand the molecular pathogenesis of CVDs in anthrax. The hub genes reported in the study can be considered potential drug targets and they can be exploited for new drug discovery.
PMID:36736801 | DOI:10.1016/j.micpath.2023.106019
North and East African mitochondrial genetic variation needs further characterization towards precision medicine
J Adv Res. 2023 Jan 31:S2090-1232(23)00034-6. doi: 10.1016/j.jare.2023.01.021. Online ahead of print.
ABSTRACT
INTRODUCTION: Mitochondria are maternally inherited cell organelles with their own genome, and perform various functions in eukaryotic cells such as energy production and cellular homeostasis. Due to their inheritance and manifold biological roles in health and disease, mitochondrial genetics serves a dual purpose of tracing the history as well as disease susceptibility of human populations across the globe. This work requires a comprehensive catalogue of commonly observed genetic variations in the mitochondrial DNAs for all regions throughout the world. So far, however, certain regions, such as North and East Africa have been understudied.
OBJECTIVES: To address this shortcoming, we have created the most comprehensive quality-controlled North and East African mitochondrial data set to date and use it for characterizing mitochondrial genetic variation in this region.
METHODS: We compiled 11 published cohorts with novel data for mitochondrial genomes from 159 Sudanese individuals. We combined these 641 mitochondrial sequences with sequences from the 1000 Genomes (n=2,504) and the Human Genome Diversity Project (n=828) and used the tool haplocheck for extensive quality control and detection of in-sample contamination, as well as Nanopore long read sequencing for haplogroup validation of 18 samples.
RESULTS: Using a subset of high-coverage mitochondrial sequences, we predict 15 potentially novel haplogroups in North and East African subjects and observe likely phylogenetic deviations from the established PhyloTree reference for haplogroups L0a1 and L2a1.
CONCLUSION: Our findings demonstrate common hitherto unexplored variants in mitochondrial genomes of North and East Africa that lead to novel phylogenetic relationships between haplogroups present in these regions. These observations call for further in-depth population genetic studies in that region to enable the prospective use of mitochondrial genetic variation for precision medicine.
PMID:36736695 | DOI:10.1016/j.jare.2023.01.021
Rule-based modelling of biological systems using regulated rewriting
Biosystems. 2023 Jan 31:104843. doi: 10.1016/j.biosystems.2023.104843. Online ahead of print.
ABSTRACT
In systems biology, models play a crucial role in understanding studied systems. There are many modelling approaches, among which rewriting systems provide a framework for describing systems on a mechanistic level. Describing biochemical processes often requires incorporating knowledge on an abstract level to simplify the system description or substitute the missing details. For this purpose, we present regulation mechanisms, an extension of this formalism with additional controls on the rewriting process. We introduce several regulation mechanisms and apply them to a rule-based language, a notation suitable for modelling biological phenomena. Finally, we demonstrate the usage of such regulations on several case studies from the biochemical domain.
PMID:36736686 | DOI:10.1016/j.biosystems.2023.104843
Fibrinogen on extracellular vesicles derived from polyhexamethylene guanidine phosphate-exposed mice induces inflammatory effects via integrin β
Ecotoxicol Environ Saf. 2023 Feb 1;252:114600. doi: 10.1016/j.ecoenv.2023.114600. Online ahead of print.
ABSTRACT
Polyhexamethylene guanidine phosphate (PHMG-p), used as a humidifier disinfectant, causes interstitial lung disease, obliterative bronchiolitis, and lung fibrosis; however, little is known about its effect on intercellular interactions. Extracellular vesicles (EVs), which carry diverse compounds including proteins, RNA, and DNA to mediate cell-to-cell communication through their paracrine effects, have been highlighted as novel factors in lung fibrogenesis. This study aimed to identify the effect of proteins on small EVs (sEVs) from bronchoalveolar lavage fluid (BALF) of the recipient cells after PHMG-p exposure. A week after intratracheal administration of PHMG-p, sEVs were isolated from BALF of tissue showing overexpressed inflammatory and fibrosis markers. To investigate the role of sEVs in inflammation, naïve macrophages were cultured with sEVs, which induced their activation. To identify sEV proteins that are associated with these responses, proteomics analysis was performed. In the gene ontology analysis, coagulation, fibrinolysis, and hemostasis were associated with the upregulated proteins in sEVs. The highest increase was observed in fibrinogen levels, which was also related to those gene ontologies. We validated role of exosomal fibrinogen in inflammation using recombinant fibrinogen and an inhibitor of the integrin, which is the binding receptor for fibrinogen. Overall, we elucidated that increased fibrinogen levels in the early sEVs-PHMG activated inflammatory response during early fibrosis. These results suggest that sEVs from the BALF of PHMG-p-exposed mice could aggravate fibrogenesis by activating naïve macrophages via various proteins in the sEVs, Furthermore, this finding will be broadening the spectrum of communicating mediators.
PMID:36736230 | DOI:10.1016/j.ecoenv.2023.114600
High-throughput co-culture system for analysis of spatiotemporal cell-cell signaling
Biosens Bioelectron. 2023 Jan 30;225:115089. doi: 10.1016/j.bios.2023.115089. Online ahead of print.
ABSTRACT
Study of spatial and temporal aspects of signaling between individual cells is essential in understanding development, the immune response, and host-pathogen interactions. We present an automated high-throughput microfluidic platform that chemically stimulates immune cells to initiate cytokine secretion, and controls the formation of signal gradients that activate neighboring cell populations. Furthermore, our system enables controlling the cell type and density based on distance, and retrieval of cells from different regions for gene expression analysis. Our device performs these tasks in 192 independent chambers to simultaneously test different co-culture conditions. We demonstrate these capabilities by creating various cellular communication scenarios between macrophages and fibroblasts in vitro. We find that spatial distribution of macrophages and heterogeneity in cytokine secretion determine spatiotemporal gene expression responses. Furthermore, we describe how gene expression dynamics depend on a cell's distance from the signaling source. Our device addresses key challenges in the study of cell-to-cell signaling, and provides high-throughput and automated analysis over a wide range of co-culture conditions.
PMID:36736159 | DOI:10.1016/j.bios.2023.115089
First assessment of Iranian pomegranate germplasm using targeted metabolites and morphological traits to develop the core collection and modeling of the current and future spatial distribution under climate change conditions
PLoS One. 2023 Feb 3;18(2):e0265977. doi: 10.1371/journal.pone.0265977. eCollection 2023.
ABSTRACT
Pomegranate has been considered a medicinal plant due to its rich nutrients and bioactive compounds. Since environmental conditions affect the amount and composition of metabolites, selecting suitable locations for cultivation would be vital to achieve optimal production. In this study, data on the diversity of targeted metabolites and morphological traits of 152 Iranian pomegranate genotypes were collected and combined in order to establish the first core collection. The multivariate analyses were conducted including principal component analysis (PCA), and cluster analysis. In addition, the current and future geographical distribution of pomegranate in Iran was predicted to identify suitable locations using the MaxEnt model. The results showed high diversity in the studied morphological and metabolic traits. The PCA results indicated that FFS, NFT, JA, and AA are the most important traits in discriminating the studied genotypes. A constructed core collection using maximization strategy consisted of 20 genotypes and accounted for 13.16% of the entire collection. Shannon-Weaver diversity index of a core collection was similar or greater than the entire collection. Evaluation of the core collection using four parameters of MD, VD, CR, and VR also indicated the maintenance of the genetic diversity of the original set. According to the MaxEnt model, altitude, average temperature of coldest quarter, and isothertmality were the key factors for the distribution of pomegranate. The most suitable areas for pomegranate cultivation were also determined which were located in arid and semi-arid regions of Iran. The geographic distribution of pomegranate in the future showed that the main provinces of pomegranate cultivation would be less affected by climatic conditions by the middle of the century. The results of this study provide valuable information for selection of elite genotypes to develop the breeding programs to obtain the cultivars with the highest levels of metabolic compounds for pharmaceutical purposes, as well as identification of the most suitable agro-ecological zones for orchard establishment.
PMID:36735649 | DOI:10.1371/journal.pone.0265977
Delineating Marker-trait Associations for Fusarium Wilt in Chickpea using Axiom® Cicer SNP Array
Phytopathology. 2023 Feb 3. doi: 10.1094/PHYTO-05-22-0164-FI. Online ahead of print.
ABSTRACT
Fusarium wilt (FW) caused by the Fusarium oxysporum f. sp. ciceri is a devastating disease of chickpea (Cicer arietinum L.). To identify promising resistant genotypes and genomic loci for FW resistance, a core set of 179 genotypes of chickpea was tested for FW reactions at seedling and reproductive stages under field as well as controlled conditions in the greenhouse. Our results revealed that at seedling stage, most of the genotypes were found resistant whereas, at the reproductive stage majority of the genotypes were found susceptible. Genotyping using a 50K Axiom®Cicer SNP Array and trait data of FW together led to the identification of 26 significant (p≤E-05) marker-trait associations (MTAs) for FW resistance. Among 26 MTAs, 12 were identified using trait data recorded in the field (3 at seedling and 9 at reproductive stage) and 14 MTAs were identified using trait data recorded under controlled conditions in the greenhouse (6 at seedling and 8 at reproductive stage). The phenotypic variation explained by these MTAs varied from 11.75 to 15.86% with an average of 13.77%. Five MTAs were classified as major, explaining more than 15% phenotypic variation for FW and two MTAs were declared stable, being identified in either two environments or at two growth stages. One of the promising stable and major MTAs (Affx_123280060) detected in field conditions at reproductive stage was also detected in greenhouse conditions at seedling and reproductive stages. The stable and major (>15% PVE) MTAs can be used in chickpea breeding programmes.
PMID:36734935 | DOI:10.1094/PHYTO-05-22-0164-FI