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1.
Nat Immunol ; 23(2): 251-261, 2022 02.
Article in English | MEDLINE | ID: mdl-35102343

ABSTRACT

Tumor necrosis factor (TNF) drives chronic inflammation and cell death in the intestine, and blocking TNF is a therapeutic approach in inflammatory bowel disease (IBD). Despite this knowledge, the pathways that protect the intestine from TNF are incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3s) protect the intestinal epithelium from TNF-induced cell death. This occurs independent of interleukin-22 (IL-22), and we identify that ILC3s are a dominant source of heparin-binding epidermal growth factor-like growth factor (HB-EGF). ILC3s produce HB-EGF in response to prostaglandin E2 (PGE2) and engagement of the EP2 receptor. Mice lacking ILC3-derived HB-EGF exhibit increased susceptibility to TNF-mediated epithelial cell death and experimental intestinal inflammation. Finally, human ILC3s produce HB-EGF and are reduced from the inflamed intestine. These results define an essential role for ILC3-derived HB-EGF in protecting the intestine from TNF and indicate that disruption of this pathway contributes to IBD.


Subject(s)
Heparin-binding EGF-like Growth Factor/immunology , Immunity, Innate/immunology , Inflammation/immunology , Intestines/immunology , Lymphocytes/immunology , Tumor Necrosis Factor-alpha/immunology , Animals , Epithelial Cells/immunology , Intestinal Mucosa/immunology , Mice , Mice, Inbred C57BL , Signal Transduction/immunology
2.
Nature ; 618(7967): 1017-1023, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37316672

ABSTRACT

The discovery and application of genome editing introduced a new era of plant breeding by giving researchers efficient tools for the precise engineering of crop genomes1. Here we demonstrate the power of genome editing for engineering broad-spectrum disease resistance in rice (Oryza sativa). We first isolated a lesion mimic mutant (LMM) from a mutagenized rice population. We then demonstrated that a 29-base-pair deletion in a gene we named RESISTANCE TO BLAST1 (RBL1) caused broad-spectrum disease resistance and showed that this mutation caused an approximately 20-fold reduction in yield. RBL1 encodes a cytidine diphosphate diacylglycerol synthase that is required for phospholipid biosynthesis2. Mutation of RBL1 results in reduced levels of phosphatidylinositol and its derivative phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). In rice, PtdIns(4,5)P2 is enriched in cellular structures that are specifically associated with effector secretion and fungal infection, suggesting that it has a role as a disease-susceptibility factor3. By using targeted genome editing, we obtained an allele of RBL1, named RBL1Δ12, which confers broad-spectrum disease resistance but does not decrease yield in a model rice variety, as assessed in small-scale field trials. Our study has demonstrated the benefits of editing an LMM gene, a strategy relevant to diverse LMM genes and crops.


Subject(s)
Diacylglycerol Cholinephosphotransferase , Disease Resistance , Gene Editing , Oryza , Plant Breeding , Plant Diseases , Disease Resistance/genetics , Gene Editing/methods , Genome, Plant/genetics , Oryza/enzymology , Oryza/genetics , Oryza/microbiology , Phosphatidylinositols/metabolism , Plant Breeding/methods , Plant Diseases/genetics , Plant Diseases/microbiology , Alleles , Phosphatidylinositol 4,5-Diphosphate/metabolism , Diacylglycerol Cholinephosphotransferase/genetics , Diacylglycerol Cholinephosphotransferase/metabolism
3.
Nature ; 609(7925): 159-165, 2022 09.
Article in English | MEDLINE | ID: mdl-35831503

ABSTRACT

RORγt is a lineage-specifying transcription factor that is expressed by immune cells that are enriched in the gastrointestinal tract and promote immunity, inflammation and tissue homeostasis1-15. However, fundamental questions remain with regard to the cellular heterogeneity among these cell types, the mechanisms that control protective versus inflammatory properties and their functional redundancy. Here we define all RORγt+ immune cells in the intestine at single-cell resolution and identify a subset of group 3 innate lymphoid cells (ILC3s) that expresses ZBTB46, a transcription factor specifying conventional dendritic cells16-20. ZBTB46 is robustly expressed by CCR6+ lymphoid-tissue-inducer-like ILC3s that are developmentally and phenotypically distinct from conventional dendritic cells, and its expression is imprinted by RORγt, fine-tuned by microbiota-derived signals and increased by pro-inflammatory cytokines. ZBTB46 restrains the inflammatory properties of ILC3s, including the OX40L-dependent expansion of T helper 17 cells and the exacerbated intestinal inflammation that occurs after enteric infection. Finally, ZBTB46+ ILC3s are a major source of IL-22, and selective depletion of this population renders mice susceptible to enteric infection and associated intestinal inflammation. These results show that ZBTB46 is a transcription factor that is shared between conventional dendritic cells and ILC3s, and identify a cell-intrinsic function for ZBTB46 in restraining the pro-inflammatory properties of ILC3s and a non-redundant role for ZBTB46+ ILC3s in orchestrating intestinal health.


Subject(s)
Immunity, Innate , Intestines , Lymphocytes , Nuclear Receptor Subfamily 1, Group F, Member 3 , Transcription Factors , Animals , Inflammation/immunology , Inflammation/pathology , Interleukins , Intestines/cytology , Intestines/immunology , Intestines/pathology , Lymphocytes/cytology , Lymphocytes/immunology , Mice , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , OX40 Ligand/metabolism , Receptors, CCR6/metabolism , Th17 Cells/cytology , Th17 Cells/immunology , Transcription Factors/metabolism , Interleukin-22
4.
Nature ; 610(7933): 744-751, 2022 10.
Article in English | MEDLINE | ID: mdl-36071169

ABSTRACT

Microbial colonization of the mammalian intestine elicits inflammatory or tolerogenic T cell responses, but the mechanisms controlling these distinct outcomes remain poorly understood, and accumulating evidence indicates that aberrant immunity to intestinal microbiota is causally associated with infectious, inflammatory and malignant diseases1-8. Here we define a critical pathway controlling the fate of inflammatory versus tolerogenic T cells that respond to the microbiota and express the transcription factor RORγt. We profiled all RORγt+ immune cells at single-cell resolution from the intestine-draining lymph nodes of mice and reveal a dominant presence of T regulatory (Treg) cells and lymphoid tissue inducer-like group 3 innate lymphoid cells (ILC3s), which co-localize at interfollicular regions. These ILC3s are distinct from extrathymic AIRE-expressing cells, abundantly express major histocompatibility complex class II, and are necessary and sufficient to promote microbiota-specific RORγt+ Treg cells and prevent their expansion as inflammatory T helper 17 cells. This occurs through ILC3-mediated antigen presentation, αV integrin and competition for interleukin-2. Finally, single-cell analyses suggest that interactions between ILC3s and RORγt+ Treg cells are impaired in inflammatory bowel disease. Our results define a paradigm whereby ILC3s select for antigen-specific RORγt+ Treg cells, and against T helper 17 cells, to establish immune tolerance to the microbiota and intestinal health.


Subject(s)
Immune Tolerance , Intestines , Lymphocytes , Microbiota , T-Lymphocytes, Regulatory , Animals , Immunity, Innate , Integrin alphaV/metabolism , Interleukin-2/immunology , Intestines/immunology , Intestines/microbiology , Lymph Nodes/cytology , Lymph Nodes/immunology , Lymphocytes/immunology , Microbiota/immunology , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Single-Cell Analysis , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Transcription Factors/metabolism , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/pathology
5.
Mol Plant Microbe Interact ; 36(7): 452-456, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36802869

ABSTRACT

Bipolaris sorokiniana, one of the most devastating hemibiotrophic fungal pathogens, causes root rot, crown rot, leaf blotching, and black embryos of gramineous crops worldwide, posing a serious threat to global food security. However, the host-pathogen interaction mechanism between B. sorokiniana and wheat remains poorly understood. To facilitate related studies, we sequenced and assembled the genome of B. sorokiniana LK93. Nanopore long reads and next generation sequencing short reads were applied in the genome assembly, and the final 36.4-Mb genome assembly contains 16 contigs with the contig N50 of 2.3 Mb. Subsequently, we annotated 11,811 protein-coding genes. Of these, 10,620 were functional genes, 258 of which were identified as secretory proteins, including 211 predicted effectors. Additionally, the 111,581-bp mitogenome of LK93 was assembled and annotated. The LK93 genomes presented in this study will facilitate research in the B. sorokiniana-wheat pathosystem for better control of crop diseases. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Subject(s)
Ascomycota , Genome, Mitochondrial , Ascomycota/genetics , Triticum/microbiology , Genome, Mitochondrial/genetics , Bipolaris/genetics , Plant Diseases/microbiology
6.
J Cell Sci ; 134(8)2021 04 15.
Article in English | MEDLINE | ID: mdl-33722979

ABSTRACT

CRISPR/Cas9-based tissue-specific knockout techniques are essential for probing the functions of genes in embryonic development and disease using zebrafish. However, the lack of capacity to perform gene-specific rescue or live imaging in the tissue-specific knockout background has limited the utility of this approach. Here, we report a robust and flexible gateway system for tissue-specific gene inactivation in neutrophils. Using a transgenic fish line with neutrophil-restricted expression of Cas9 and ubiquitous expression of single guide (sg)RNAs targeting rac2, specific disruption of the rac2 gene in neutrophils is achieved. Transient expression of sgRNAs targeting rac2 or cdk2 in the neutrophil-restricted Cas9 line also results in significantly decreased cell motility. Re-expressing sgRNA-resistant rac2 or cdk2 genes restores neutrophil motility in the corresponding knockout background. Moreover, active Rac and force-bearing F-actins localize to both the cell front and the contracting tail during neutrophil interstitial migration in an oscillating fashion that is disrupted when rac2 is knocked out. Together, our work provides a potent tool that can be used to advance the utility of zebrafish in identifying and characterizing gene functions in a tissue-specific manner.


Subject(s)
Neutrophils , Zebrafish , Animals , Animals, Genetically Modified , CRISPR-Cas Systems/genetics , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Neutrophils/metabolism , Zebrafish/genetics , Zebrafish/metabolism , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , rac GTP-Binding Proteins/metabolism
7.
Trends Immunol ; 41(8): 721-733, 2020 08.
Article in English | MEDLINE | ID: mdl-32646594

ABSTRACT

Group 3 innate lymphoid cells (ILC3s) have emerged as master regulators of intestinal health and tissue homeostasis in mammals. Through a diverse array of cytokines and cellular interactions, ILC3s crucially orchestrate lymphoid organogenesis, promote tissue protection or regeneration, facilitate antimicrobial responses, and directly regulate adaptive immunity. Further, translational studies have found that ILC3 responses are altered in the intestine of defined patient populations with chronic infectious, inflammatory, or metabolic diseases. Therefore, it is essential to broadly understand the signals that activate, suppress, or fine-tune ILC3s in the gut. Here, we discuss recent exciting advances in this field, integrate them into our current understanding of ILC3 biology, and highlight fundamental gaps in knowledge that require additional investigation.


Subject(s)
Gastrointestinal Microbiome , Immunity, Innate , Lymphocytes , Adaptive Immunity/immunology , Animals , Gastrointestinal Microbiome/immunology , Homeostasis , Humans , Immunity, Innate/immunology , Lymphocytes/cytology , Lymphocytes/immunology
8.
J Cell Sci ; 133(17)2020 09 04.
Article in English | MEDLINE | ID: mdl-32788232

ABSTRACT

Neutrophils rely on glycolysis for energy production. How mitochondria regulate neutrophil function is not fully understood. Here, we report that mitochondrial outer membrane protein Mitofusin 2 (MFN2) regulates neutrophil homeostasis and chemotaxis in vivoMfn2-deficient neutrophils are released from the hematopoietic tissue, trapped in the vasculature in zebrafish embryos, and not capable of chemotaxis. Consistent with this, human neutrophil-like cells that are deficient for MFN2 fail to arrest on activated endothelium under sheer stress or perform chemotaxis on 2D surfaces. Deletion of MFN2 results in a significant reduction of neutrophil infiltration to the inflamed peritoneal cavity in mice. Mechanistically, MFN2-deficient neutrophil-like cells display disrupted mitochondria-ER interaction, heightened intracellular Ca2+ levels and elevated Rac activation after chemokine stimulation. Restoring a mitochondria-ER tether rescues the abnormal Ca2+ levels, Rac hyperactivation and chemotaxis defect resulting from MFN2 depletion. Finally, inhibition of Rac activation restores chemotaxis in MFN2-deficient neutrophils. Taken together, we have identified that MFN2 regulates neutrophil migration via maintaining the mitochondria-ER interaction to suppress Rac activation, and uncovered a previously unrecognized role of MFN2 in regulating cell migration and the actin cytoskeleton.This article has an associated First Person interview with the first authors of the paper.


Subject(s)
Neutrophils , Zebrafish , Actin Cytoskeleton , Adhesives , Animals , Cell Movement , Mice
9.
Eur J Immunol ; 51(2): 393-407, 2021 02.
Article in English | MEDLINE | ID: mdl-33029793

ABSTRACT

Cytomegalovirus (CMV)-based vaccines show promising effects against chronic infections in nonhuman primates. Therefore, we examined the potential of hepatitis B virus (HBV) vaccines based on mouse CMV (MCMV) vectors expressing the small HBsAg. Immunological consequences of vaccine virus attenuation were addressed by either replacing the dispensable gene m157 ("MCMV-HBsȍ) or the gene M27 ("ΔM27-HBs"), the latter encodes a potent IFN antagonist targeting the transcription factor STAT2. M27 was chosen, since human CMV encodes an analogous gene product, which also induced proteasomal STAT2 degradation by exploiting Cullin RING ubiquitin ligases. Vaccinated mice were challenged with HBV through hydrodynamic injection. MCMV-HBs and ΔM27-HBs vaccination achieved accelerated HBV clearance in serum and liver as well as robust HBV-specific CD8+ T-cell responses. When we explored the therapeutic potential of MCMV-based vaccines, especially the combination of ΔM27-HBs prime and DNA boost vaccination resulted in increased intrahepatic HBs-specific CD8+ T-cell responses and HBV clearance in persistently infected mice. Our results demonstrated that vaccines based on a replication competent MCMV attenuated through the deletion of an IFN antagonist targeting STAT2 elicit robust anti-HBV immune responses and mediate HBV clearance in mice in prophylactic and therapeutic immunization regimes.


Subject(s)
Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/immunology , Hepatitis B virus/immunology , Hepatitis B, Chronic/immunology , Muromegalovirus/immunology , Animals , Antiviral Agents/immunology , CD8-Positive T-Lymphocytes/immunology , Cells, Cultured , Female , Hepatitis B, Chronic/virology , Immunization/methods , Interferons/immunology , Liver/immunology , Liver/virology , Male , Mice , Mice, Inbred C57BL , STAT2 Transcription Factor/immunology , Vaccination/methods , Virus Replication/immunology
10.
J Appl Microbiol ; 133(2): 422-435, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35352442

ABSTRACT

AIM: The objective of this research was to screen fungal isolates originally isolated from cotton plants and measure their effects on the interactions between soybean and two aboveground pests (cabbage looper; Trichoplusia ni and soybean looper; Chrysodeixis includens) as well as a belowground pest (soybean cyst nematode; Heterodera glycines). METHODS AND RESULTS: For aboveground pests, we measured the leaf area consumed and larval weight. For our belowground pest tests, we measured shoot height, shoot fresh weight, root fresh weight and number of cysts. Out of the 50 fungal isolates tested, we tested 30 fungi in the interaction with cabbage looper, 36 for soybean looper, 41 for soybean cyst nematode. We tested 23 isolates against all pests and identified multiple isolates that significantly changed the response of pests on inoculated soybean plants versus controls. CONCLUSIONS: We identified three fungal isolates that significantly reduced both leaf area consumed aboveground by caterpillars and number of cysts produced belowground by nematodes. These isolates were an Epicoccum italicum, a Chaetomium undulatum and a Stemphylium majusculum. SIGNIFICANCE AND IMPACT OF STUDY: Overall, this study provides important insights into plant-fungal interactions and their effect on both above- and belowground pests. This study also highlights an important first step towards harnessing the potential of microbial inoculates as a tool for integrated pest management in soybeans.


Subject(s)
Cysts , Fabaceae , Moths , Tylenchoidea , Animals , Fungi , Glycine max
11.
Int J Mol Sci ; 23(17)2022 Aug 23.
Article in English | MEDLINE | ID: mdl-36076919

ABSTRACT

Arbuscular mycorrhizal fungi (AMF) are important symbiotic microorganisms in soil that engage in symbiotic relationships with legumes, resulting in mycorrhizal symbiosis. Establishment of strong symbiotic relationships between AMF and legumes promotes the absorption of nitrogen by plants. Ammonium nitrogen can be directly utilised by plants following ammonium transport, but there are few reports on ammonium transporters (AMTs) promoting ammonium nitrogen transport during AM symbiosis. Lotus japonicus is a typical legume model plant that hosts AMF. In this study, we analysed the characteristics of the Lotus japonicus ammonium transporter LjAMT2;2, and found that it is a typical ammonium transporter with mycorrhizal-induced and ammonium nitrogen transport-related cis-acting elements in its promoter region. LjAMT2;2 facilitated ammonium transfer in yeast mutant supplement experiments. In the presence of different nitrogen concentrations, the LjAMT2;2 gene was significantly upregulated following inoculation with AMF, and induced by low nitrogen. Overexpression of LjAMT2;2 increased the absorption of ammonium nitrogen, resulting in doubling of nitrogen content in leaves and roots, thus alleviating nitrogen stress and promoting plant growth.


Subject(s)
Ammonium Compounds , Lotus , Mycorrhizae , Fungi , Mycorrhizae/genetics , Nitrogen , Plant Proteins/genetics , Plant Roots/genetics , Saccharomyces cerevisiae/genetics , Symbiosis/genetics
12.
Biochem Biophys Res Commun ; 558: 196-201, 2021 06 18.
Article in English | MEDLINE | ID: mdl-32962860

ABSTRACT

Phosphate transporters (PHTs) are well-known for their roles in phosphate uptake in plants. However, their actions in imparting plant growth in plants are still not so clear. In our previous study, we observed that maize PHT1 gene ZmPt9 plays a significant role in phosphate uptake. In this study, we further characterized ZmPt9 in response to low phosphate condition through ZmPt9 promoter inductive analysis by GUS staining and quantification. To elucidate the function of ZmPt9, we generated overexpression plant in Arabidopsis. ZmPt9 overexpressing Arabidopsis plants conferred small leaves and early flowering compared with the wild-type plants. In addition, ZmPt9 can complement the late flowering phenotype of Arabidopsis mutant pht1;2. The qRT-PCR analysis revealed that overexpression of ZmPt9 in Arabidopsis changed expression levels of some flowering-related genes. Further expressed detection of hormone related genes revealed that GA and auxin maybe the main determinant for growth influences of ZmPt9. In conclusion, these results suggest that apart from phosphate transport activity, ZmPt9 can be further exploited for improving crops growth.


Subject(s)
Arabidopsis/genetics , Genes, Plant , Phosphate Transport Proteins/genetics , Plant Proteins/genetics , Zea mays/genetics , Arabidopsis/growth & development , Arabidopsis/metabolism , Cell Division/genetics , Flowers/genetics , Flowers/growth & development , Flowers/metabolism , Gene Expression Regulation, Developmental , Gene Expression Regulation, Plant , Mutation , Phenotype , Phosphate Transport Proteins/metabolism , Phosphates/metabolism , Plant Leaves/cytology , Plant Leaves/genetics , Plant Leaves/metabolism , Plant Proteins/metabolism , Plant Roots/genetics , Plant Roots/growth & development , Plant Roots/metabolism , Plants, Genetically Modified , Promoter Regions, Genetic , Up-Regulation , Zea mays/metabolism
13.
J Nat Prod ; 83(2): 202-209, 2020 02 28.
Article in English | MEDLINE | ID: mdl-32049520

ABSTRACT

Dithiolopyrrolones are microbial natural products containing a disulfide or thiosulfonate bridge embedded in a unique bicyclic structure. By interfering with zinc ion homeostasis in living cells, they show strong antibacterial activity against a variety of bacterial pathogens, as well as potent cytotoxicity against human cancer cells. In the current study, two new dithiolopyrrolones, pyrroloformamide C (3) and pyrroloformamide D (4), were isolated from Streptomyces sp. CB02980, together with the known pyrroloformamides 1 and 2. The biosynthetic gene cluster for pyrroloformamides was identified from Streptomyces sp. CB02980, which shared high sequence similarity with those of dithiolopyrrolones, including holomycin and thiolutin. Gene replacement of pyfE, which encodes a nonribosomal peptide synthetase (NRPS), abolished the production of 1-4. Overexpression of pyfN, a type II thioesterase gene, increased the production of 1 and 2. Genome neighborhood network analysis of the characterized and orphan gene clusters of dithiolopyrrolones revealed a unified mechanism for their biosynthesis, involving an iterative-acting NRPS and a set of conserved tailoring enzymes for the bicyclic core formation.


Subject(s)
Anti-Bacterial Agents/isolation & purification , Bacterial Proteins/genetics , Biological Products/chemistry , Formamides/isolation & purification , Heterocyclic Compounds, 2-Ring/isolation & purification , Lactams/chemistry , Peptide Synthases/genetics , Anti-Bacterial Agents/chemistry , Bacterial Proteins/chemistry , Formamides/chemistry , Heterocyclic Compounds, 2-Ring/chemistry , Humans , Molecular Structure , Multigene Family , Peptide Synthases/chemistry , Streptomyces/chemistry , Streptomyces/genetics
14.
Am J Emerg Med ; 38(11): 2303-2307, 2020 11.
Article in English | MEDLINE | ID: mdl-31780188

ABSTRACT

BACKGROUND: Acute appendicitis (AA) is one of the most common diseases faced by the surgeon in the emergency department. In clinical practice, how to diagnose patients with AA accurately is still challenging. METHODS: We conducted a prospective study of 84 patients who presented in the emergency department with suspected AA and measured fecal calprotectin (FC) value. The final diagnosis of AA was independently determined without reference to the test results of FC. Then, we retrospectively analyzed the FC value for identifying AA. RESULTS: FC value in patients with AA were significantly higher than that in patients without AA (240.5 vs. 68.5 ug/g, P < 0.001). Receiver-operating characteristic analyses demonstrated FC value to be highly sensitive and specific for the diagnosis of AA, as indicated by an overall area under the curve (AUC) of 0.928 (500 times of boot strap estimated 95% CI, 0.855-0.972), with an optimal cut off point of 106 ug/g. FC levels in 26 patients with simple AA were significantly lower than it in the 14 patients with suppurative AA (206 vs. 304ug/g, P = 0.001). CONCLUSIONS: FC test provides a sensitive, convenient and economical method to help facilitate the diagnosis of AA in emergency department. Especially for hospitals without computed tomography equipment or patients who are not suitable to exposed to radiation, FC test is of great significance for improving the diagnostic accuracy of AA.


Subject(s)
Appendicitis/diagnosis , Feces/chemistry , Leukocyte L1 Antigen Complex/analysis , Adult , Aged , Biomarkers/analysis , Case-Control Studies , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Male , Middle Aged , Prospective Studies , ROC Curve , Retrospective Studies
15.
Immunol Rev ; 273(1): 29-47, 2016 09.
Article in English | MEDLINE | ID: mdl-27558326

ABSTRACT

Neutrophils play fundamental roles in both acute and chronic inflammatory conditions, and directly contribute to the immune pathologies in both infectious and autoimmune ailments. MicroRNAs (miRs) regulate homeostasis in health and disease by fine tuning the expression of a network of genes through post-transcriptional regulation. Many miRs are expressed in restricted tissues, regulated by stress and disease, and are emerging as mediators for intercellular communication. MiR profiles have been recently utilized as biomarkers for diagnosis and prognostic purposes. In addition, several miRs are in clinical development for various diseases. A short list of miRs that regulate hematopoiesis and neutrophil development is identified. Unfortunately, very limited information is available regarding how miRs regulate neutrophil migration and activation in vivo. Extensive future work is required, especially in animal models such as mice, to illustrate the pivotal and complex miR-mediated regulatory network. In addition, zebrafish, a vertebrate model organism with conserved innate immunity, potentiated by the availability of imaging and genetic tools, will provide a platform for rapid discovery and characterization of miRs that are relevant to neutrophilic inflammation. Advances in this field are expected to provide the foundation for highly selective miR-based therapy to manipulate neutrophils in infection and inflammatory disorders.


Subject(s)
Immune System Diseases/immunology , Immunotherapy/methods , Inflammation/immunology , MicroRNAs/genetics , Neutrophil Activation/genetics , Neutrophils/physiology , RNA Processing, Post-Transcriptional , Animals , Cell Movement/genetics , Disease Models, Animal , Humans , Immune System Diseases/therapy , Immunity, Innate , Immunotherapy/trends , Inflammation/therapy , Mice , Zebrafish
16.
Plant Physiol ; 176(2): 1835-1849, 2018 02.
Article in English | MEDLINE | ID: mdl-29242377

ABSTRACT

The calcium-dependent protein kinase OsCPK4 has been demonstrated to play important roles in salt and drought tolerance, plant growth, and development in rice (Oryza sativa). However, little is known about molecular mechanisms underlying OsCPK4 function in rice immunity. In this study, we demonstrated that the generation of oxidative burst and pathogenesis-related gene expression triggered by microbe-associated molecular patterns were significantly enhanced in the oscpk4 mutants. These mutant lines are more resistant to bacterial blight and fungal blast diseases than the wild-type plants, indicating that OsCPK4 negatively regulates innate immunity in rice. OsCPK4 was further identified to interact with a receptor-like cytoplasmic kinase OsRLCK176. OsRLCK176 accumulation is negatively regulated by OsCPK4. Interestingly, the kinase-dead OsCPK4 promotes OsRLCK176 degradation more strongly than the wild-type protein. OsCPK4 and OsRLCK176 mutually phosphorylate each other and form a feedback loop. Moreover, the kinase activity and phosphorylation of OsCPK4 and OsRLCK176 contribute to the stability of OsRLCK176. These findings indicate that the kinase-inactive OsCPK4 promotes OsRLCK176 degradation and restricts plant defenses, whereas the activation of OsCPK4-OsRLCK176 phosphorylation circuit invalidates the OsRLCK176 degradation machinery, thus enhancing plant immunity. Collectively, the study proposes a novel defense buffering mechanism mediated by OsCPK4, which fine-tunes microbe-associated molecular pattern-triggered immunity in rice.


Subject(s)
Oryza/genetics , Plant Diseases/immunology , Plant Immunity , Protein Kinases/metabolism , Oryza/immunology , Phosphorylation , Plant Diseases/microbiology , Plant Proteins/genetics , Plant Proteins/metabolism , Protein Kinases/genetics
17.
BMC Plant Biol ; 18(1): 315, 2018 Nov 29.
Article in English | MEDLINE | ID: mdl-30497407

ABSTRACT

BACKGROUND: Foxtail millet (Setaria italica L. P. Beauv) has been considered as a tractable model crop in recent years due to its short growing cycle, lower amount of repetitive DNA, inbreeding nature, small diploid genome, and outstanding abiotic stress-tolerance characteristics. With modern agriculture facing various adversities, it's urgent to dissect the mechanisms of how foxtail millet responds and adapts to drought and stress on the proteomic-level. RESULTS: In this research, a total of 2474 differentially expressed proteins were identified by quantitative proteomic analysis after subjecting foxtail millet seedlings to drought conditions. 321 of these 2474 proteins exhibited significant expression changes, including 252 up-regulated proteins and 69 down-regulated proteins. The resulting proteins could then be divided into different categories, such as stress and defense responses, photosynthesis, carbon metabolism, ROS scavenging, protein synthesis, etc., according to Gene Ontology annotation. Proteins implicated in fatty acid and amino acid metabolism, polyamine biosynthesis, hormone metabolism, and cell wall modifications were also identified. These obtained differential proteins and their possible biological functions under drought stress all suggested that various physiological and metabolic processes might function cooperatively to configure a new dynamic homeostasis in organisms. The expression patterns of five drought-responsive proteins were further validated using western blot analysis. The qRT-PCR was also carried out to analyze the transcription levels of 21 differentially expressed proteins. The results showed large inconsistency in the variation between proteins and the corresponding mRNAs, which showed once again that post-transcriptional modification performs crucial roles in regulating gene expression. CONCLUSION: The results offered a valuable inventory of proteins that may be involved in drought response and adaption, and provided a regulatory network of different metabolic pathways under stress stimulation. This study will illuminate the stress tolerance mechanisms of foxtail millet, and shed some light on crop germplasm breeding and innovation.


Subject(s)
Setaria Plant/metabolism , Blotting, Western , Chromatography, High Pressure Liquid , Dehydration , Gas Chromatography-Mass Spectrometry , Gene Expression Regulation, Plant , Plant Proteins/isolation & purification , Plant Proteins/metabolism , Plant Proteins/physiology , Proteomics , Real-Time Polymerase Chain Reaction , Setaria Plant/physiology
18.
J Antimicrob Chemother ; 69(6): 1470-3, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24532683

ABSTRACT

OBJECTIVES: The objective of this study was to identify the mechanism responsible for the horizontal transfer of transposon Tn2010 in Streptococcus pneumoniae, and the genomic alterations introduced by the transfer process. METHODS: Tn2010 was identified using PCR in 15 clinical isolates of S. pneumoniae with erythromycin resistance. S. pneumoniae and Enterococcus faecalis isolates were used as recipient cells in mating and transformation experiments to test the conjugative transferability and transformability of Tn2010. Whole-genome sequencing was used to assess the effects of the Tn2010 transfer on recipient genomes. The biological cost of the horizontal acquisition of Tn2010 and additional genomic changes was investigated by growth competition experiments. RESULTS: Tn2010 was transformed at a frequency of 3 × 10(-7) transformants per cfu, whereas no transconjugants were detected using S. pneumoniae or E. faecalis as recipient cells. Genome analysis showed that many other recombinations were scattered throughout the genome of the transformants in addition to transposon Tn2010. The transformants demonstrated a negligible fitness cost compared with the wild-type strain. CONCLUSIONS: Tn2010 tended to be transferred by transformation rather than conjugation in S. pneumoniae, and the spread of Tn2010 could have a profound effect on the evolution of the genome. The acquisition of Tn2010 with negligible fitness cost may facilitate spread of the transposon.


Subject(s)
DNA Transposable Elements , Drug Resistance, Bacterial/genetics , Evolution, Molecular , Genome, Bacterial , Macrolides/pharmacology , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/genetics , Chromosome Mapping , Chromosomes, Bacterial , Humans , Recombination, Genetic
19.
Opt Lett ; 39(6): 1382-5, 2014 Mar 15.
Article in English | MEDLINE | ID: mdl-24690793

ABSTRACT

A theory for nonreciprocal phase shift caused by cross coupling generated in a polarization maintaining (PM) fiber optic gyroscope (FOG) under the combined action of magnetic and temperature fields is proposed. The magnetic-thermal coupling in the FOG originates from the interaction of the magnetic field, fiber twist, birefringence caused by thermal stress, and the intrinsic and bending birefringence of the fiber. The cross coupling changes with temperature. When the PM fiber has a diameter of 250 µm, beat length of 3 mm, length of 500 m, twist rate of 1 rad/m, and optical source wavelength of 1310 nm, the maximum degree of magnetic-thermal coupling generated by a 1 mT radial magnetic field within the temperature range of -20°C to 60°C is -5.47%.

20.
Environ Sci Pollut Res Int ; 31(6): 8703-8718, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38180669

ABSTRACT

Due to their extremely toxic properties, 226Ra and it daughters (222Rn, 210Pb, and 210Po) in drinking groundwater require monitoring. Recent studies have reported exceptionally high levels of natural 210Po (up to 10,000 Bq/m3), 226Ra, and 222Rn isotopes in groundwater. This study aims to provide background data on 226Ra and its daughter radionuclides in the typical agricultural-industrial Dongshan Bay (DSB) before the construction of Zhangzhou Nuclear Power Plant (Zhangzhou NPP). The measurement results indicate that no abnormally high activities of 210Po and 210Pb were detected in the investigated wells. Strong positive correlations between 210Pb and 210Po, as well as between 222Rn and 210Pb activities, suggest that the origins of 210Pb and 210Po in groundwater are strongly influenced by the decay of the parent radionuclides 222Rn and 210Pb, respectively. In the DSB coastal zone groundwater, significant deficiencies of 210Po relative to 210Pb and 210Pb relative to 222Rn were observed, providing further evidence that 210Po and 210Pb are also effectively scavenged due to their geochemical properties (specifically particle affinity) within the groundwater-aquifer system. A systematic comparison among all relevant water bodies in the DSB revealed that the activity concentrations of 210Pb and 210Po in groundwater were the highest, except for rainwater. Based on the evaluation of 210Pb sources, the results imply that submarine groundwater discharge (SGD) is an important pathway for transferring radionuclides (such as 210Pb) from land to the nearshore marine environment, even though the study area has a lower 210Pb background groundwater. By considering all the 210Pb's sources in the DSB, we found low 210Pb background groundwater discharge still needs to be taken into account for small-scale bays. This is because SGD was calculated to be one of the most important 210Pb sources in the bay during observation season. Regardless of whether the system is in a normal state or a nuclear accident emergency state, greater attention should be paid to the groundwater discharge of radionuclides into the ocean.


Subject(s)
Groundwater , Nuclear Family , Humans , Bays/chemistry , Lead , Groundwater/chemistry , Radioisotopes
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