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1.
J Neurosci ; 44(30)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-38897723

ABSTRACT

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.


Subject(s)
Feeding Behavior , Habenula , Light , Animals , Male , Mice , Habenula/physiology , Feeding Behavior/physiology , Dorsal Raphe Nucleus/physiology , Humans , Mice, Inbred C57BL , Eating/physiology , Neural Pathways/physiology , Rats , Serotonergic Neurons/physiology , Nerve Net/physiology , Darkness
2.
Chemotherapy ; 69(1): 11-22, 2024.
Article in English | MEDLINE | ID: mdl-37339610

ABSTRACT

INTRODUCTION: At present, there are several studies on low-dose apatinib combined with chemotherapy as a second-line treatment of advanced gastric cancer (AGC), but the conclusions are controversial. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of low-dose apatinib combined with chemotherapy as a second-line treatment of AGC. METHODS: Nine databases were searched for records on apatinib combined with chemotherapy in treating AGC from inception to June 2022. The observation group received low-dose apatinib combined with chemotherapy, while the controls received chemotherapy alone or other non-placebo treatments. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. The relative risk (RR) and weighted mean difference (WMD) were used as effect sizes. RESULTS: Eight studies involving 679 patients were included in this meta-analysis. The results of the meta-analysis showed that the observation group was superior to the controls in terms of ORR (RR = 1.38, 95% confidence interval [CI]: 1.05-1.81, p = 0.02), DCR (RR = 1.35, 95% CI: 1.20-1.53, p < 0.001), OS (WMD = 4.72, 95% CI: 0.71-8.72, p < 0.001), and PFS (WMD = 2.67, 95% CI: 1.7-3.63, p < 0.001). There were no significant differences between the two groups in adverse events of any grade except hypertension (RR = 2.82, 95% CI: 2.07-3.84, p < 0.001), hand-mouth syndrome (RR = 1.84, 95% CI: 1.84-2.48, p < 0.001), and proteinuria (RR = 3.63, 95% CI: 2.31-5.7, p < 0.001). CONCLUSION: Low-dose apatinib combined with chemotherapy as a second-line therapy is more effective in improving the efficacy of AGC compared to chemotherapy alone. However, this option has the potential to increase the risk of hypertension, hand-mouth syndrome, and proteinuria.


Subject(s)
Antineoplastic Agents , Hypertension , Pyridines , Stomach Neoplasms , Humans , Antineoplastic Agents/adverse effects , Stomach Neoplasms/drug therapy , Hypertension/chemically induced , Hypertension/drug therapy , Proteinuria/chemically induced , Proteinuria/drug therapy
3.
Sensors (Basel) ; 23(13)2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37448039

ABSTRACT

Multiple unmanned aerial vehicles (UAVs) have a greater potential to be widely used in UAV-assisted IoT applications. UAV formation, as an effective way to improve surveillance and security, has been extensively of concern. The leader-follower approach is efficient for UAV formation, as the whole formation system needs to find only the leader's trajectory. This paper studies the leader-follower surveillance system. Owing to different scenarios and assignments, the leading velocity is dynamic. The inevitable communication time delays resulting from information sending, communicating and receiving process bring challenges in the design of real-time UAV formation control. In this paper, the design of UAV formation tracking based on deep reinforcement learning (DRL) is investigated for high mobility scenarios in the presence of communication delay. To be more specific, the optimization UAV formation problem is firstly formulated to be a state error minimization problem by using the quadratic cost function when the communication delay is considered. Then, the delay-informed Markov decision process (DIMDP) is developed by including the previous actions in order to compensate the performance degradation induced by the time delay. Subsequently, an extended-delay informed deep deterministic policy gradient (DIDDPG) algorithm is proposed. Finally, some issues, such as computational complexity analysis and the effect of the time delay are discussed, and then the proposed intelligent algorithm is further extended to the arbitrary communication delay case. Numerical experiments demonstrate that the proposed DIDDPG algorithm can significantly alleviate the performance degradation caused by time delays.


Subject(s)
Algorithms , Intelligence , Markov Chains , Policy , Records
4.
Entropy (Basel) ; 24(2)2022 Feb 21.
Article in English | MEDLINE | ID: mdl-35205598

ABSTRACT

With the rapid development of UAV technology, the research of optimal UAV formation tracking has been extensively studied. However, the high maneuverability and dynamic network topology of UAVs make formation tracking control much more difficult. In this paper, considering the highly dynamic features of uncertain time-varying leader velocity and network-induced delays, the optimal formation control algorithms for both near-equilibrium and general dynamic control cases are developed. First, the discrete-time error dynamics of UAV leader-follower models are analyzed. Next, a linear quadratic optimization problem is formulated with the objective of minimizing the errors between the desired and actual states consisting of velocity and position information of the follower. The optimal formation tracking problem of near-equilibrium cases is addressed by using a backward recursion method, and then the results are further extended to the general dynamic case where the leader moves at an uncertain time-varying velocity. Additionally, angle deviations are investigated, and it is proved that the similar state dynamics to the general case can be derived and the principle of control strategy design can be maintained. By using actual real-world data, numerical experiments verify the effectiveness of the proposed optimal UAV formation-tracking algorithm in both near-equilibrium and dynamic control cases in the presence of network-induced delays.

5.
Int J Mol Sci ; 22(23)2021 Nov 24.
Article in English | MEDLINE | ID: mdl-34884502

ABSTRACT

σ54 factor (RpoN), a type of transcriptional regulatory factor, is widely found in pathogenic bacteria. It binds to core RNA polymerase (RNAP) and regulates the transcription of many functional genes in an enhancer-binding protein (EBP)-dependent manner. σ54 has two conserved functional domains: the activator-interacting domain located at the N-terminal and the DNA-binding domain located at the C-terminal. RpoN directly binds to the highly conserved sequence, GGN10GC, at the -24/-12 position relative to the transcription start site of target genes. In general, bacteria contain one or two RpoNs but multiple EBPs. A single RpoN can bind to different EBPs in order to regulate various biological functions. Thus, the overlapping and unique regulatory pathways of two RpoNs and multiple EBP-dependent regulatory pathways form a complex regulatory network in bacteria. However, the regulatory role of RpoN and EBPs is still poorly understood in phytopathogenic bacteria, which cause economically important crop diseases and pose a serious threat to world food security. In this review, we summarize the current knowledge on the regulatory function of RpoN, including swimming motility, flagella synthesis, bacterial growth, type IV pilus (T4Ps), twitching motility, type III secretion system (T3SS), and virulence-associated phenotypes in phytopathogenic bacteria. These findings and knowledge prove the key regulatory role of RpoN in bacterial growth and pathogenesis, as well as lay the groundwork for further elucidation of the complex regulatory network of RpoN in bacteria.


Subject(s)
Bacteria/pathogenicity , Bacterial Proteins/metabolism , Enhancer Elements, Genetic , Gene Expression Regulation, Bacterial , RNA Polymerase Sigma 54/metabolism , Type III Secretion Systems/metabolism , Virulence , Animals , Bacterial Proteins/genetics , Humans , RNA Polymerase Sigma 54/genetics , Type III Secretion Systems/genetics
6.
Mol Plant Microbe Interact ; 33(10): 1196-1208, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32720873

ABSTRACT

The degenerate GGDEF/EAL domain protein Filp was previously shown to function as a cyclic di-GMP (c-di-GMP) signal receptor through its specific interaction with an atypical PilZ domain protein PilZX3 (formerly PXO_02715) and that this interaction is involved in regulating virulence in Xanthomonas oryzae pv. oryzae. As a step toward understanding the regulatory role of Filp/PilZX3-mediated c-di-GMP signaling in the virulence of X. oryzae pv. oryzae, differentially expressed proteins (DEPs) downstream of Filp/PilZX3 were identified by isobaric tagging for relative and absolute quantitation (iTRAQ). A total of 2,346 proteins were identified, of which 157 displayed significant differential expression in different strains. Western blot and quantitative reverse transcription-PCR analyses showed that the expression of HrrP (histidine kinase-response regulator hybrid protein), PhrP (PhoPQ-regulated protein), ProP (prophage Lp2 protein 6) were increased in the ∆filp, ∆pilZX3, and ∆filp∆pilZX3 mutant strains, while expression of CheW1 (chemotaxis protein CheW1), EdpX2 (the second EAL domain protein identified in X. oryzae pv. oryzae), HGdpX2 (the second HD-GYP domain protein identified in X. oryzae pv. oryzae) was decreased in all mutant strains compared with that in the wild type, which was consistent with the iTRAQ data. Deletion of the hrrP and proP genes resulted in significant increases in virulence, whereas deletion of the cheW1, hGdpX2, or tdrX2 genes resulted in decreased virulence. Enzyme assays indicated that EdpX2 and HGdpX2 were active phosphodiesterases (PDEs). This study provides a proteomic description of putative regulatory pathway of Filp and PilZX3 and characterized novel factors that contributed to the virulence of X. oryzae pv. oryzae regulated by c-di-GMP signaling.


Subject(s)
Bacterial Proteins/genetics , Cyclic GMP/analogs & derivatives , Oryza/microbiology , Plant Diseases/microbiology , Xanthomonas/pathogenicity , Cyclic GMP/chemistry , Gene Expression Regulation, Bacterial , Proteomics , Signal Transduction , Virulence , Xanthomonas/genetics
7.
Mol Plant Microbe Interact ; 32(6): 729-739, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30589364

ABSTRACT

PdeR, a response regulator of the two-component system (TCS) with the cognate histidine kinase PdeK, has been shown to be an active phosphodiesterase (PDE) for intracellular cyclic dimeric guanosine monophosphate (c-di-GMP) turnover and positively regulates the virulence of Xanthomonas oryzae pv. oryzae, the causal pathogen of bacterial blight of rice. To further reveal the key components and pathways involved in the PdeR-mediated c-di-GMP regulation of virulence, 16 PdeR-interacting proteins were identified, using the yeast two-hybrid (Y2H) assay. Among them, PXO_04421 (named as TriP, a putative transcriptional regulator interacting with PdeR) was verified via Y2H and glutathione-S-transferase pull-down assays, and its regulatory functions in bacterial virulence and exopolysaccharide (EPS) production were assessed by biochemical and genetic analysis. The REC domain of TriP specifically interacted with the EAL domain of PdeR. TriP promoted the PDE activity of PdeR to degrade c-di-GMP in the presence of PdeK. In-frame deletion in triP abolished the polar localization of PdeR in the cell. Notably, the ∆triP mutant showed significantly reduced virulence on susceptible rice leaves and impaired EPS production compared with wild type, whereas the double mutant ∆triP∆pdeR, like ∆pdeR, caused shorter lesion lengths and produced less EPS than ∆triP. In addition, cross-complementation showed in trans expression of pdeR in ∆triP restored its EPS production to near wild-type levels but not vice versa. Taken together, our results suggest that TriP is a novel regulator that is epistatic to PdeR in positively regulating virulence expression in X. oryzae pv. oryzae.


Subject(s)
Oryza , Virulence , Xanthomonas , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial , Oryza/microbiology , Phosphoric Diester Hydrolases/metabolism , Plant Diseases/microbiology , Virulence/genetics , Xanthomonas/enzymology , Xanthomonas/genetics , Xanthomonas/pathogenicity
8.
Plant Cell Physiol ; 59(6): 1234-1247, 2018 Jun 01.
Article in English | MEDLINE | ID: mdl-29566243

ABSTRACT

Limiting nitrogen (N) supply contributes to improved resistance to bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) in susceptible rice (Oryza sativa). To understand the regulatory roles of microRNAs (miRNAs) in this phenomenon, 63 differentially expressed overlapping miRNAs in response to Xoo infection and N limitation stress in rice were identified through deep RNA sequencing and stem-loop quantitative real-time PCR. Among these, miR169o was further assessed as a typical overlapping miRNA through the overexpression of the miR169o primary gene. Osa-miR169o-OX plants were taller, and had more biomass accumulation with significantly increased nitrate and total amino acid contents in roots than the wild type (WT). Transcript level assays showed that under different N supply conditions, miR169o oppositely regulated NRT2, and this is reduced under normal N supply conditions but remarkably induced under N-limiting stress. On the other hand, osa-miR169o-OX plants also displayed increased disease lesion lengths and reduced transcriptional levels of defense gene (PR1b, PR10a, PR10b and PAL) compared with the WT after inoculation with Xoo. In addition, miR169o impeded Xoo-mediated NRT transcription. Therefore, the overlapping miR169o contributes to increase N use efficiency and negatively regulates the resistance to BB in rice. Consistently, transient expression of NF-YA genes in rice protoplasts promoted the transcripts of PR genes and NRT2 genes, while it reduced the transcripts of NRT1 genes. Our results provide novel and additional insights into the co ordinated regulatory mechanisms of cross-talk between Xoo infection and N deficiency responses in rice.


Subject(s)
Disease Resistance , Gene Expression Regulation, Plant , MicroRNAs/genetics , Nitrogen/deficiency , Oryza/genetics , Plant Diseases/immunology , Xanthomonas/physiology , Gene Expression , Nitrogen/metabolism , Oryza/microbiology , Oryza/physiology , Plant Diseases/microbiology , RNA, Plant/genetics
9.
Appl Environ Microbiol ; 84(22)2018 11 15.
Article in English | MEDLINE | ID: mdl-30217836

ABSTRACT

In Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice, there are over 20 genes encoding GGDEF, EAL, and HD-GYP domains, which are potentially involved in the metabolism of second messenger c-di-GMP. In this study, we focused on the characterization of an EAL domain protein, EdpX1. Deletion of the edpX1 gene resulted in a 2-fold increase in the intracellular c-di-GMP levels, which were restored to the wild-type levels in the complemented ΔedpX1(pB-edpX1) strain, demonstrating that EdpX1 is an active phosphodiesterase (PDE) in X. oryzae pv. oryzae. In addition, colorimetric assays further confirmed the PDE activity of EdpX1 by showing that the E153A mutation at the EAL motif strongly reduced its activity. Virulence assays on the leaves of susceptible rice showed that the ΔedpX1 mutant was severely impaired in causing disease symptoms. In trans expression of wild-type edpX1, but not edpX1E153A, was able to complement the weakened virulence phenotype. These results indicated that an active EAL domain is required for EdpX1 to regulate the virulence of X. oryzae pv. oryzae. We then demonstrated that the ΔedpX1 mutant was defective in secreting exopolysaccharide (EPS) and forming biofilms. The expression of edpX1 in the ΔedpX1 mutant, but not edpX1E153A, restored the defective phenotypes to near-wild-type levels. In addition, we observed that EdpX1-green fluorescent protein (EdpX1-GFP) exhibited multiple subcellular localization foci, and this pattern was dependent on its transmembrane (TM) region, which did not seem to directly contribute to the regulatory function of EdpX1. Thus, we concluded that EdpX1 exhibits PDE activity to control c-di-GMP levels, and its EAL domain is necessary and sufficient for its regulation of virulence in X. oryzae pv. oryzae.IMPORTANCE Bacteria utilize c-di-GMP as a second messenger to regulate various biological functions. The synthesis and degradation of c-di-GMP are catalyzed by GGDEF domains and an EAL or HD-GYP domain, respectively. Multiple genes encoding these domains are often found in one bacterial strain. For example, in the genome of X. oryzae pv. oryzae PXO99A, 26 genes encoding proteins containing these domains were identified. Therefore, to fully appreciate the complexity and specificity of c-di-GMP signaling in X. oryzae pv. oryzae, the enzymatic activities and regulatory functions of each GGDEF, EAL, and HD-GYP domain protein need to be elucidated. In this study, we showed that the EAL domain protein EdpX1 is a major PDE to regulate diverse virulence phenotypes through the c-di-GMP signaling pathway.


Subject(s)
Bacterial Proteins/metabolism , Biofilms , Oryza/microbiology , Phosphoric Diester Hydrolases/metabolism , Plant Diseases/microbiology , Polysaccharides, Bacterial/biosynthesis , Xanthomonas/enzymology , Xanthomonas/pathogenicity , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Cyclic GMP/analogs & derivatives , Cyclic GMP/metabolism , Gene Expression Regulation, Bacterial , Mutation , Phosphoric Diester Hydrolases/chemistry , Phosphoric Diester Hydrolases/genetics , Protein Domains , Signal Transduction , Virulence , Xanthomonas/genetics , Xanthomonas/physiology
10.
New Phytol ; 220(1): 219-231, 2018 10.
Article in English | MEDLINE | ID: mdl-29949665

ABSTRACT

Xanthomonas oryzae pv. oryzae is the causative agent of rice bacterial leaf blight. While the type III secretion system of X. oryzae pv. oryzae is essential for virulence, the biochemical activities and virulence mechanisms of non-transcription activator-like (non-TAL) effectors delivered by this system are largely unknown. Here, by screening for non-TAL effectors that contribute to X. oryzae pv. oryzae virulence, we revealed that Xanthomonas outer protein K (XopK) inhibits pathogen-associated molecular pattern-triggered immunity upstream of mitogen-activated protein kinase cascades. Specifically, XopK interacted with and directly ubiquitinated rice somatic embryogenic receptor kinase 2 (OsSERK2), resulting in its degradation. Accordingly, mutation of a putative ubiquitin-conjugation enzyme (E2) binding site abolished XopK-induced degradation of OsSERK2 and compromised XopK-dependent virulence. As crucial immune regulators associated with a multitude of immune receptors, SERKs have been shown to be perturbed by Pseudomonas effectors via different mechanisms. Our study revealed a distinct perturbation mechanism of SERK activity via ubiquitination achieved by Xanthomonas non-TAL effector.


Subject(s)
Bacterial Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Xanthomonas/enzymology , Xanthomonas/pathogenicity , Arabidopsis/immunology , Arabidopsis/microbiology , Disease Resistance/immunology , MAP Kinase Signaling System , Mutation/genetics , Oryza/microbiology , Pathogen-Associated Molecular Pattern Molecules/metabolism , Plant Diseases/immunology , Plant Diseases/microbiology , Plant Immunity , Plant Proteins/metabolism , Protein Binding , Proteolysis , Protoplasts/metabolism
11.
BMC Microbiol ; 17(1): 171, 2017 Aug 09.
Article in English | MEDLINE | ID: mdl-28793882

ABSTRACT

BACKGROUND: Bacterial blight of rice caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most important crop diseases in the world. More insights into the mechanistic regulation of bacterial pathogenesis will help us identify novel molecular targets for developing effective disease control strategies. A large flagellar gene cluster is regulated under a three-tiered hierarchy by σ54 factor RpoN2 and its activator FleQ, and σ28 factor FliA. A hypothetical protein gene fliTX is located upstream of rpoN2, however, how it is regulated and how it is related to bacterial behaviors remain to be elucidated. RESULTS: Sequence alignment analysis indicated that FliTX in Xoo is less well conserved compared with FliT proteins in Escherichia coli, Salmonella typhimurium, and Pseudomonas fluorescens. Co-transcription of fliTX with a cytosolic chaperone gene fliS and an atypical PilZ-domain gene flgZ in an operon was up-regulated by RpoN2/FleQ and FliA. Significantly shorter filament length and impaired swimming motility were observed in ∆fliTX compared with those in the wildtype strain. ∆fliTX also demonstrated reduced disease lesion length and in planta growth in rice, attenuated ability of induction of hypersensitive response (HR) in nonhost tobacco, and down-regulation of type III secretion system (T3SS)-related genes. In trans expression of fliTX gene in ∆fliTX restored these phenotypes to near wild-type levels. CONCLUSIONS: This study demonstrates that RpoN2- and FliA-regulated fliTX is indispensible for flagellar motility and virulence and provides more insights into mechanistic regulation of T3SS expression in Xoo.


Subject(s)
Bacterial Proteins/genetics , Flagella/physiology , Gene Expression Regulation, Bacterial , Plant Diseases/microbiology , RNA Polymerase Sigma 54/metabolism , Sigma Factor/metabolism , Xanthomonas/metabolism , Xanthomonas/pathogenicity , Bacterial Proteins/metabolism , Flagella/genetics , Oryza/microbiology , RNA Polymerase Sigma 54/genetics , Sigma Factor/genetics , Type III Secretion Systems/genetics , Type III Secretion Systems/metabolism , Virulence , Xanthomonas/genetics
12.
Opt Express ; 25(20): 23597-23604, 2017 Oct 02.
Article in English | MEDLINE | ID: mdl-29041311

ABSTRACT

A high efficient broadband polarization converter is an important component in integrated miniaturized optical systems, but its performances is often restricted by the material structures, metallic metasurfaces for polarization control in transmission mode never achieved efficiency above 0.5. Herein, we theoretically demonstrate that metallic metasurfaces constructed by thick cross-shaped particles can realize a high efficient polarization transformation over a broadband. We investigated the resonant properties of designed matesurfaces and found that the interaction between double FP cavity resonances and double bulk magnetic resonances is the main reason to generate a high transmissivity over a broadband. In addition, through using four resonances effect and tuning the anisotropic optical response, we realized a high efficient (> 0.85) quarter-wave plate at the wavelength range from 1175nm to 1310nm and a high efficient (> 0.9) half-wave plate at the wavelength range from 1130nm to 1230nm. The proposed polarization converters may have many potential applications in integrated polarization conversion devices and optical data storage systems.

13.
BMC Microbiol ; 16(1): 269, 2016 11 08.
Article in English | MEDLINE | ID: mdl-27825304

ABSTRACT

BACKGROUND: To facilitate infection, Xanthomonas oryzae pv. oryzae (Xoo), the bacterial blight pathogen of rice, needs to degrade hydrogen peroxide (H2O2) generated by the host defense response via a mechanism that is mediated by the transcriptional regulator OxyR. The catalase (CAT) gene catB has previously been shown to belong to the OxyR regulon in Xoo. However, its expression patterns and function in H2O2 detoxification and bacterial pathogenicity on rice remain to be elucidated. RESULTS: The catB gene encodes a putative catalase and is highly conserved in the sequenced strains of Xanthomonas spp. ß-galactosidase analysis and electrophoretic mobility shift assays (EMSA) showed that OxyR positively regulated the transcription of catB by directly binding to its promoter region. The quantitative real-time PCR (qRT-PCR) assays revealed that the expression levels of catB and oxyR were significantly induced by H2O2. Deletion of catB or oxyR drastically impaired bacterial viability in the presence of extracellular H2O2 and reduced CAT activity, demonstrating that CatB and OxyR contribute to H2O2 detoxification in Xoo. In addition, ΔcatB and ΔoxyR displayed shorter bacterial blight lesions and reduced bacterial growth in rice compared to the wild-type stain, indicating that CatB and OxyR play essential roles in the virulence of Xoo. CONCLUSIONS: Transcription of catB is enhanced by OxyR in response to exogenous H2O2. CatB functions as an active catalase that is required for the full virulence of Xoo in rice.


Subject(s)
Bacterial Proteins/metabolism , Catalase/metabolism , Gene Expression Regulation, Bacterial , Hydrogen Peroxide/metabolism , Oryza/microbiology , Plant Diseases/microbiology , Xanthomonas/enzymology , Xanthomonas/pathogenicity , Bacterial Proteins/genetics , Catalase/genetics , Hydrogen Peroxide/toxicity , Virulence , Xanthomonas/genetics
14.
Plant Physiol ; 167(3): 1076-86, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25609555

ABSTRACT

Pathogen-associated molecular patterns (PAMPs) are recognized by plant pattern recognition receptors to activate PAMP-triggered immunity (PTI). Mitogen-activated protein kinases (MAPKs), as well as other cytoplasmic kinases, integrate upstream immune signals and, in turn, dissect PTI signaling via different substrates to regulate defense responses. However, only a few direct substrates of these signaling kinases have been identified. Here, we show that PAMP perception enhances phosphorylation of BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1 (BES1), a transcription factor involved in brassinosteroid (BR) signaling pathway, through pathogen-induced MAPKs in Arabidopsis (Arabidopsis thaliana). BES1 interacts with MITOGEN-ACTIVATED PROTEIN KINASE6 (MPK6) and is phosphorylated by MPK6. bes1 loss-of-function mutants display compromised resistance to bacterial pathogen Pseudomonas syringae pv tomato DC3000. BES1 S286A/S137A double mutation (BES1(SSAA)) impairs PAMP-induced phosphorylation and fails to restore bacterial resistance in bes1 mutant, indicating a positive role of BES1 phosphorylation in plant immunity. BES1 is phosphorylated by glycogen synthase kinase3 (GSK3)-like kinase BR-insensitive2 (BIN2), a negative regulator of BR signaling. BR perception inhibits BIN2 activity, allowing dephosphorylation of BES1 to regulate plant development. However, BES1(SSAA) does not affect BR-mediated plant growth, suggesting differential residue requirements for the modulation of BES1 phosphorylation in PTI and BR signaling. Our study identifies BES1 as a unique direct substrate of MPK6 in PTI signaling. This finding reveals MAPK-mediated BES1 phosphorylation as another BES1 modulation mechanism in plant cell signaling, in addition to GSK3-like kinase-mediated BES1 phosphorylation and F box protein-mediated BES1 degradation.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/enzymology , Arabidopsis/immunology , Mitogen-Activated Protein Kinases/metabolism , Nuclear Proteins/metabolism , Plant Immunity , Arabidopsis/microbiology , Brassinosteroids/pharmacology , DNA-Binding Proteins , Disease Resistance/immunology , Enzyme Activation/drug effects , Flagellin/metabolism , Hypocotyl/drug effects , Hypocotyl/growth & development , Phosphorylation/drug effects , Phosphoserine/metabolism , Plant Diseases/immunology , Plant Diseases/microbiology , Plant Immunity/drug effects , Plant Roots/drug effects , Plant Roots/growth & development , Protein Binding/drug effects , Pseudomonas syringae/drug effects , Substrate Specificity/drug effects
15.
Appl Environ Microbiol ; 81(13): 4358-67, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25911481

ABSTRACT

The PilZ domain proteins have been demonstrated to be one of the major types of receptors mediating cyclic di-GMP (c-di-GMP) signaling pathways in several pathogenic bacteria. However, little is known about the function of PilZ domain proteins in c-di-GMP regulation of virulence in the bacterial blight pathogen of rice Xanthomonas oryzae pv. oryzae. Here, the roles of PilZ domain proteins PXO_00049 and PXO_02374 in c-di-GMP binding, regulation of virulence and motility, and subcellular localization were characterized in comparison with PXO_02715, identified previously as an interactor with the c-di-GMP receptor Filp to regulate virulence. The c-di-GMP binding motifs in the PilZ domains were conserved in PXO_00049 and PXO_02374 but were less well conserved in PXO_02715. PXO_00049 and PXO_02374 but not PXO_02715 proteins bound to c-di-GMP with high affinity in vitro, and the R(141) and R(10) residues in the PilZ domains of PXO_00049 and PXO_02374, respectively, were crucial for c-di-GMP binding. Gene deletion of PXO_00049 and PXO_02374 resulted in significant increases in virulence and hrp gene transcription, indicating their negative regulation of virulence via type III secretion system expression. All mutants showed significant changes in sliding motility but not exopolysaccharide production and biofilm formation. In trans expression of the full-length open reading frame (ORF) of each gene in the relevant mutants led to restoration of the phenotype to wild-type levels. Moreover, PXO_00049 and PXO_02374 displayed mainly multisite subcellular localizations, whereas PXO_02715 showed nonpolar distributions in the X. oryzae pv. oryzae cells. Therefore, this study demonstrated the different functions of the PilZ domain proteins in mediation of c-di-GMP regulation of virulence and motility in X. oryzae pv. oryzae.


Subject(s)
Bacterial Proteins/metabolism , Cyclic GMP/analogs & derivatives , Gene Expression Regulation, Bacterial , Locomotion , Xanthomonas/physiology , Xanthomonas/pathogenicity , Amino Acid Motifs , Binding Sites , Cyclic GMP/metabolism , Gene Deletion , Genetic Complementation Test , Protein Binding , Virulence
16.
Microb Pathog ; 85: 50-7, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26065383

ABSTRACT

Acetyltransferases catalyze an important process for sugar or protein modification. In the genome of Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight of rice, there are 32 acetyltransferase-encoding genes belonging to different families. In this work, we focused on PXO_00987, which encodes a putative acetyltransferase in the flagellar regulon. We found that mutation of PXO_00987 gene abolished the glycosylation of wild-type flagellin protein of Xoo. In addition, the PXO_00987 mutant showed enhanced swimming motility, and decreased exopolysaccharide production and biofilm formation. Virulence assays demonstrated that the PXO_00987 mutant caused shorter disease length on rice leaves, suggesting that the function of PXO_00987 contributes to the pathogenesis of Xoo.


Subject(s)
Acetyltransferases/metabolism , Bacterial Proteins/metabolism , Biofilms , Flagellin/metabolism , Polysaccharides, Bacterial/biosynthesis , Xanthomonas/enzymology , Acetyltransferases/chemistry , Acetyltransferases/genetics , Amino Acid Sequence , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Flagellin/genetics , Gene Expression Regulation, Bacterial , Glycosylation , Molecular Sequence Data , Oryza/microbiology , Plant Diseases/microbiology , Regulon , Sequence Alignment , Virulence , Xanthomonas/genetics , Xanthomonas/pathogenicity , Xanthomonas/physiology
17.
Mol Plant Microbe Interact ; 27(6): 578-89, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24548063

ABSTRACT

Degenerate GGDEF and EAL domain proteins represent major types of cyclic diguanylic acid (c-di-GMP) receptors in pathogenic bacteria. Here, we characterized a FimX-like protein (Filp) which possesses both GGDEF and EAL domains in Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight of rice. Both in silico analysis and enzyme assays indicated that the GGDEF and EAL domains of Filp were degenerate and enzymatically inactive. However, Filp bound to c-di-GMP efficiently within the EAL domain, where Q(477), E(653), and F(654) residues were crucial for the binding. Deletion of the filp gene in X. oryzae pv. oryzae resulted in attenuated virulence in rice and reduced type III secretion system (T3SS) gene expression. Complementation analysis with different truncated proteins indicated that REC, PAS, and EAL domains but not the GGDEF domain were required for the full activity of Filp in vivo. In addition, a PilZ-domain protein (PXO_02715) was identified as a Filp interactor by yeast two-hybrid and glutathione-S-transferase pull-down assays. Deletion of the PXO_02715 gene demonstrated changes in bacterial virulence and T3SS gene expression similar to Δfilp. Moreover, both mutants were impaired in their ability to induce hypersensitive response in nonhost plants. Thus, we concluded that Filp was a novel c-di-GMP receptor of X. oryzae pv. oryzae, and its function to regulate bacterial virulence expression might be via the interaction with PXO_02715.


Subject(s)
Bacterial Proteins/metabolism , Cyclic GMP/analogs & derivatives , Gene Expression Regulation, Bacterial , Oryza/microbiology , Plant Diseases/microbiology , Xanthomonas/pathogenicity , Amino Acid Sequence , Bacterial Proteins/genetics , Biofilms , Cyclic GMP/metabolism , Fimbriae, Bacterial/metabolism , Molecular Sequence Data , Mutation , Plant Leaves/microbiology , Polysaccharides, Bacterial/metabolism , Protein Binding , Protein Structure, Tertiary , Sequence Alignment , Sequence Homology, Amino Acid , Signal Transduction , Nicotiana/microbiology , Two-Hybrid System Techniques , Virulence , Xanthomonas/genetics , Xanthomonas/physiology
18.
Lab Med ; 55(1): 1-7, 2024 Jan 06.
Article in English | MEDLINE | ID: mdl-37172311

ABSTRACT

OBJECTIVE: To evaluate the diagnostic value of circulating microRNA-29 (miR-29) in digestive system malignant neoplasms by meta-analysis. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science to collect studies, published through September 2022, on the diagnostic value of miR-29 in digestive system tumors. RESULTS: We included 7 studies in this meta-analysis, including colorectal cancer, esophageal squamous cell carcinomas, and cholangiocarcinoma. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.64 (95% CI, 0.53-0.74), 0.83 (0.60-0.94), 3.75 (1.42-9.91), 0.44 (0.31-0.61), and 8.63 (2.54-29.26), respectively. The area under the summary receiver operating characteristic curve was 0.75. The sensitivity of miR-29 derived from serum was higher than that of miR-29 derived from plasma for malignant digestive system tumors (0.71 vs 0.54; P = .04). CONCLUSION: This meta-analysis suggests that the circulating miR-29 family has good diagnostic performance for digestive system malignant tumors, with moderate sensitivity and good specificity.


Subject(s)
Digestive System Neoplasms , MicroRNAs , Humans , Biomarkers, Tumor , Digestive System Neoplasms/diagnosis , ROC Curve , Sensitivity and Specificity
19.
Microbiol Resour Announc ; 13(8): e0029124, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-38967467

ABSTRACT

Here, we report the complete genome sequence of Erwinia amylovora PBI209 that causes fire blight isolated from a necrotic flower of Pyrus sinkiangensis in Xinjiang, China. The genome consists of 3,800,955 bp, with 3,403 protein-coding genes and a guanine-cytosine content of 53.61%.

20.
Microbiol Resour Announc ; 13(3): e0107023, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38299808

ABSTRACT

Here, we report the complete genome sequence for Pseudomonas syringae pv. actinidiae strain Yunnan3.2, which was isolated from diseased kiwifruit grown in Yunnan province, China. The complete genome of Yunnan3.2 comprises a 6,564,315-bp chromosome with a GC content of 58.41% and a circular plasmid (74,466 bp).

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