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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35553340

RESUMO

The inhibition of calcineurin (PP2B) with tacrolimus (FK506) or cyclosporin A (CsA), two frequently used immunosuppressive drugs after organ transplantation, has been shown to stimulate cation-coupled Cl- cotransporters such as NCC and NKCC2. Also, the stimulation of NCC induced by CsA or FK506 may be responsible for PP2B-inhibition-induced hypertension and hyperkalemia. The aim of the present study is to test whether acute application of FK506 or CsA also stimulates the basolateral K+ channels in the distal convoluted tubule (DCT) thereby activating NCC expression/activity. We first used patch-clamp technique to examine the effect of FK506 or CsA on the basolateral Kir4.1/Kir5.1 activity in the DCT. Acutely addition of FK506 (5-10 uM) stimulates the 40 pS K+ (Kir4.1/Kir5.1 heterotetramer) channel activity in the DCT and increases the NPo from 1.6 to 2.6. Moreover, acutely addition of FK506 (10 uM) increases the whole-cell K+ currents from 1180 pA to 2050 pA in the DCT cells. As consequence of the stimulation of Kir4.1/Kir5.1, K-currents (IK ) reversal potential (an index of the membrane potential) becomes more negative in FK506 treated DCT than untreated (-73 mV vs -62 mV). To examine whether FK506-induced stimulation of Kir4.1/Kir5.1 in the DCT requires the FKBP12 (12 kDa FK506 binding protein), we then examined the effect of FK506 on the basolateral K+ channels in the DCT1 of kidney-tubule-specific (Ks)-FKBP12 KO mice. The control and Ks-FKBP12 KO mice were treated with FK506 (0.75 mg/Kg BW) by peritoneal injection 30 min before experiments. The stimulatory effect of FK506 on Kir4.1/Kir5.1 of the DCT is observed only in the control but is absent in Ks-FKBP12 KO mice, suggesting the effect of FK506 is due to the inhibition of PP2B. Moreover, we have used the whole-cell recording technique to examine the effect of CsA on the Ba2+ -sensitive K+ currents in the control and FKBP12-deficient mice because CsA-induced inhibition of PP2B requires binding to cyclophilin but not to FKBP12. We observed that CsA treatment (3 mg/Kg BW by peritoneal injection 30 min before experiments) significantly increases the whole-cell K+ currents in both control and Ks-FKBP12 KO mice. Fluorescence image shows that CsA treatment for 30 min increased the expression of Kir4.1 and pNCC (Serine 71) in the basolateral membrane and apical membrane, respectively. To determine whether the activation of the basolateral K+ channel activity in the DCT is essential for FK506-induced stimulation of NCC expression, we next examined the effect of FK506 treatment on the expression of pNCC and tNCC in the control (Kcnj10flox/flox ) and in kidney-tubule-specific (Ks-Kir4.1) KO mice. Acute FK506 treatment (peritoneal injection of FK506 at 0.75 mg/Kg BW) robustly increases the expression of pNCC and tNCC. However, the stimulatory effect of FK506 on NCC is blunted in Ks-Kir4.1 KO mice, suggesting the role of Kir4.1 in mediating PP2B-inhibition induced stimulation of NCC. We conclude that acute inhibition of PP2B stimulates the basolateral Kir4.1/Kir5.1 activity of the DCT and NCC and that the acute effect of PP2B inhibition on NCC is partially achieves by stimulation of the basolateral Kir4.1/Kir5.1.

2.
Am J Transl Res ; 14(4): 2317-2330, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559376

RESUMO

OBJECTIVES: TNM staging of gastric cancer (GC) is useful in predicting prognosis, but its definition is only possible after surgery. It is therefore desirable to develop a method that can predict prognosis and assist management options before surgery. METHODS: This study investigated 110 GC patients after radical gastrectomy and followed-up for 136 months. Patients' complete clinicopathological data were collected and gastroscopically biopsied or surgically resected tissues were examined for the expression of Her-2, nm-23, CEA and phosphorylated Stat3 (p-Stat3) using immunohistochemistry (IHC). Univariate and multivariate ROC curves, Kaplan-Meier survival curves, and SPSS Version 22.0 and R (version 3.6.1) statistical software were used to analyze the data. RESULTS: Three major findings were observed: (1) Tissue levels of p-Stat3, Her-2, CEA and nm-23 were correlated with GC patients' survival probability termed as survival prediction power (SPP). (2) Using 5-year survival as an end-point, the SPP of the p-Stat3+Her-2 combination was stronger (AUC=0.867) than that of TNM staging (AUC=0.755). (3) Using cut-off values derived from ROC curves, Kaplan-Meier analyses showed that the p-Stat3+Her-2 molecular combination could clearly predict overall survival rates between the predictive low-risk patients (69.2%) and the predictive high-risk patients (13.2%) with a discriminative difference as high as 56.0%. CONCLUSIONS: We conclude that area under the ROC curve (AUC) can be used to quantify SPP powers for biomarkers, making cross-comparisons possible among different survival predictors. This study has first established a multi-factor survival prediction model by which the p-Stat3+Her-2 combination has the best discriminative capability to differentiate low-risk patients from high-risk patients in terms of survival prognosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35478378

RESUMO

Verticillium dahliae is a notorious soil-borne pathogen that enters hosts through the roots and proliferates in the plant water-conducting elements to cause Verticillium wilt. Historically, Verticillium wilt symptoms have been explained by vascular occlusion, due to the accumulation of mycelia and plant biomacromolecule aggregation, and also by phytotoxicity caused by pathogen-secreted toxins. Beyond the direct cytotoxicity of some members of the secretome, this review systematically discusses the roles of the V. dahliae secretome in vascular occlusion, including the deposition of polysaccharides as an outcome of plant cell wall destruction, the accumulation of fungal mycelia, and modulation of plant defence responses. By modulating plant defences and hormone levels, the secretome manipulates the vascular environment to induce Verticillium wilt. Thus, the secretome of V. dahliae colludes with plant defence responses to modulate Verticillium wilt symptoms, and thereby bridges the historical concepts of both toxin production by the pathogen and vascular occlusion as the cause of wilting symptoms.

4.
Signal Transduct Target Ther ; 7(1): 131, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459215

RESUMO

Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors. Genome-wide association combined with clonal lineage tracing and clinical trials have demonstrated that innate and adaptive immune responses can promote or quell atherosclerosis. Several signaling pathways, that are associated with the inflammatory response, have been implicated within atherosclerosis such as NLRP3 inflammasome, toll-like receptors, proprotein convertase subtilisin/kexin type 9, Notch and Wnt signaling pathways, which are of importance for atherosclerosis development and regression. Targeting inflammatory pathways, especially the NLRP3 inflammasome pathway and its regulated inflammatory cytokine interleukin-1ß, could represent an attractive new route for the treatment of atherosclerotic diseases. Herein, we summarize the knowledge on cellular participants and key inflammatory signaling pathways in atherosclerosis, and discuss the preclinical studies targeting these key pathways for atherosclerosis, the clinical trials that are going to target some of these processes, and the effects of quelling inflammation and atherosclerosis in the clinic.


Assuntos
Aterosclerose , Inflamassomos , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Estudo de Associação Genômica Ampla , Humanos , Inflamassomos/metabolismo , Inflamassomos/uso terapêutico , Inflamação/complicações , Inflamação/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais/genética
5.
Mol Plant Pathol ; 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35363930

RESUMO

The arms race between fungal pathogens and plant hosts involves recognition of fungal effectors to induce host immunity. Although various fungal effectors have been identified, the effector functions of ribonucleases are largely unknown. Herein, we identified a ribonuclease secreted by Verticillium dahliae (VdRTX1) that translocates into the plant nucleus to modulate immunity. The activity of VdRTX1 causes hypersensitive response (HR)-related cell death in Nicotiana benthamiana and cotton. VdRTX1 possesses a signal peptide but is unlikely to be an apoplastic effector because its nuclear localization in the plant is necessary for cell death induction. Knockout of VdRTX1 significantly enhanced V. dahliae virulence on tobacco while V. dahliae employs the known suppressor VdCBM1 to escape the immunity induced by VdRTX1. VdRTX1 homologs are widely distributed in fungi but transient expression of 24 homologs from other fungi did not yield cell death induction, suggesting that this function is specific to the VdRTX1 in V. dahliae. Expression of site-directed mutants of VdRTX1 in N. benthamiana leaves revealed conserved ligand-binding sites that are important for VdRTX1 function in inducing cell death. Thus, VdRTX1 functions as a unique HR-inducing effector in V. dahliae that contributes to the activation of plant immunity.

6.
PLoS One ; 17(3): e0265132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320283

RESUMO

Vascular smooth muscle cell (VSMC) subpopulations relevant to vascular disease and injury repair have been depicted in healthy vessels and atherosclerosis profiles. However, whether VSMC subpopulation associated with vascular homeostasis exists in the healthy artery and how are their nature and fate in vascular remodeling remains elusive. Here, using single-cell RNA-sequencing (scRNA-seq) to detect VSMC functional heterogeneity in an unbiased manner, we showed that VSMC subpopulations in healthy artery presented transcriptome diversity and that there was significant heterogeneity in differentiation state and development within each subpopulation. Notably, we detected an independent subpopulation of VSMCs that highly expressed regulator of G protein signaling 5 (RGS5), upregulated the genes associated with inhibition of cell proliferation and construction of cytoskeleton compared with the general subpopulation, and mainly enriched in descending aorta. Additionally, the proportion of RGS5high VSMCs was markedly decreased or almost disappeared in the vascular tissues of neointimal formation, abdominal aortic aneurysm and atherosclerosis. Specific spatiotemporal characterization of RGS5high VSMC subpopulation suggested that this subpopulation was implicated in vascular homeostasis. Together, our analyses identify homeostasis-relevant transcriptional signatures of VSMC subpopulations in healthy artery, which may explain the regional vascular resistance to atherosclerosis at some extent.


Assuntos
Aterosclerose , Músculo Liso Vascular , Proteínas RGS/metabolismo , Aterosclerose/metabolismo , Proliferação de Células , Células Cultivadas , Proteínas de Ligação ao GTP/metabolismo , Humanos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Neointima/metabolismo
7.
Chin Med Sci J ; 37(1): 52-59, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35256049

RESUMO

Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.


Assuntos
Iodeto Peroxidase/genética , Doença de Kashin-Bek , Estudos de Casos e Controles , Humanos , Doença de Kashin-Bek/genética , Metilação , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas
8.
Front Microbiol ; 13: 852571, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35283850

RESUMO

Verticillium dahliae is a destructive soil-borne pathogen of many economically important dicots. The genetics of pathogenesis in V. dahliae has been extensively studied. Spt-Ada-Gcn5 acetyltransferase complex (SAGA) is an ATP-independent multifunctional chromatin remodeling complex that contributes to diverse transcriptional regulatory functions. As members of the core module in the SAGA complex in Saccharomyces cerevisiae, Ada1, together with Spt7 and Spt20, play an important role in maintaining the integrity of the complex. In this study, we identified homologs of the SAGA complex in V. dahliae and found that deletion of the Ada1 subunit (VdAda1) causes severe defects in the formation of conidia and microsclerotia, and in melanin biosynthesis and virulence. The effect of VdAda1 on histone acetylation in V. dahliae was confirmed by western blot analysis. The deletion of VdAda1 resulted in genome-wide alteration of the V. dahliae transcriptome, including genes encoding transcription factors and secreted proteins, suggesting its prominent role in the regulation of transcription and virulence. Overall, we demonstrated that VdAda1, a member of the SAGA complex, modulates multiple physiological processes by regulating global gene expression that impinge on virulence and survival in V. dahliae.

9.
BMC Biol ; 20(1): 34, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130883

RESUMO

BACKGROUND: In insects, airborne chemical signals are mainly detected by two receptor families, odorant receptors (ORs) and ionotropic receptors (IRs). Functions of ORs have been intensively investigated in Diptera and Lepidoptera, while the functions and evolution of the more ancient IR family remain largely unexplored beyond Diptera. RESULTS: Here, we identified a repertoire of 26 IRs from transcriptomes of female and male antennae, and ovipositors in the moth Agrotis segetum. We observed that a large clade formed by IR75p and IR75q expansions is closely related to the acid-sensing IRs identified in Diptera. We functionally assayed each of the five AsegIRs from this clade using Xenopus oocytes and found that two receptors responded to the tested ligands. AsegIR75p.1 responded to several compounds but hexanoic acid was revealed to be the primary ligand, and AsegIR75q.1 responded primarily to octanoic acid, and less so to nonanoic acid. It has been reported that the C6-C10 medium-chain fatty acids repel various insects including many drosophilids and mosquitos. We show that the C6-C10 medium-chain fatty acids elicited antennal responses of both sexes of A. segetum, while only octanoic acid had repellent effect to the moths in a behavioral assay. In addition, using fluorescence in situ hybridization, we demonstrated that the five IRs and their co-receptor AsegIR8a are not located in coeloconic sensilla as found in Drosophila, but in basiconic or trichoid sensilla. CONCLUSIONS: Our results significantly expand the current knowledge of the insect IR family. Based on the functional data in combination with phylogenetic analysis, we propose that subfunctionalization after gene duplication plays an important role in the evolution of ligand specificities of the acid-sensing IRs in Lepidoptera.


Assuntos
Brassica napus , Dípteros , Mariposas , Receptores Odorantes , Animais , Antenas de Artrópodes , Caprilatos , Dípteros/genética , Feminino , Hibridização in Situ Fluorescente , Proteínas de Insetos/genética , Ligantes , Masculino , Mariposas/genética , Filogenia , Receptores Odorantes/genética
10.
BMC Biol ; 20(1): 55, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35197059

RESUMO

BACKGROUND: Verticillium dahliae is a fungal pathogen that causes a vascular wilt on many economically important crops. Common fungal extracellular membrane (CFEM) domain proteins including secreted types have been implicated in virulence, but their roles in this pathogen are still unknown. RESULTS: Nine secreted small cysteine-rich proteins (VdSCPs) with CFEM domains were identified by bioinformatic analyses and their differential suppression of host immune responses were evaluated. Two of these proteins, VdSCP76 and VdSCP77, localized to the plant plasma membrane owing to their signal peptides and mediated broad-spectrum suppression of all immune responses induced by typical effectors. Deletion of either VdSCP76 or VdSCP77 significantly reduced the virulence of V. dahliae on cotton. Furthermore, VdSCP76 and VdSCP77 suppressed host immunity through the potential iron binding site conserved in CFEM family members, characterized by an aspartic acid residue in seven VdSCPs (Asp-type) in contrast with an asparagine residue (Asn-type) in VdSCP76 and VdSCP77. V. dahliae isolates carrying the Asn-type CFEM members were more virulent on cotton than those carrying the Asp-type. CONCLUSIONS: In the iron-insufficient xylem, V. dahliae is likely to employ the Asp-type CFEM members to chelate iron, and Asn-type CFEM members to suppress immunity, for successful colonization and propagation in host plants.


Assuntos
Verticillium , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ferro/metabolismo , Doenças das Plantas/microbiologia , Verticillium/metabolismo , Virulência
11.
Quant Imaging Med Surg ; 12(1): 207-214, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34993072

RESUMO

BACKGROUND: The present study aimed to compare the clinical results and pathological diagnostic quality of percutaneous transhepatic cholangiobiopsy for biliary obstruction using biopsy forceps (BFs) of varying diameter. METHODS: A total of 57 patients with obstructive jaundice who underwent percutaneous transhepatic cholangiobiopsy and drainage with 1 of 2 BFs diameters (6.0-mm BFs, n=30; 4.5-mm BFs, n=27) between February 2018 and May 2019 were retrospectively assessed. BFs were compared in terms of their sample quality, diagnostic accuracy, sensitivity, specificity, number of passes, and complication rate. RESULTS: All 57 patients underwent the procedure successfully and the technical success rate was 100%. The 6.0- and 4.5-mm BFs demonstrated a diagnostic accuracy of 80% (24/30) and 85% (23/27), respectively (P=0.733), and a sensitivity of 78% (22/28) and 86% (22/26), respectively (P=0.729). The specificity of both the 6.0- and 4.5-mm BFs was 100%. The complication rate was 10% (3/30) with the 6.0-mm BFs and 19% (5/27) with the 4.5-mm BFs (P=0.456). The mean number of biopsies was 2.9±0.6 with the 6.0-mm BFs compared with 3.6±1.0 with the 4.5-mm BFs (P<0.001). The 6.0-mm BFs provided a larger biopsy size and a less crushed specimen compared with the 4.5-mm BFs. The overall tissue scores were 5.2±0.8 with 6.0-mm BFs and 4.5±1.0 with 4.5-mm BFs (P=0.012). CONCLUSIONS: There was no statistically significant difference in the clinical results between the 2 BFs in the context of percutaneous transhepatic cholangiobiopsy. Superior samples were obtained using the 6.0-mm BFs, with a fewer number of passes. The complication rate did not increase compared with the 4.5-mm BFs.

12.
Microbiol Res ; 257: 126962, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35042052

RESUMO

Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. However, these functions have not been assessed in Verticillium dahliae, a soil-borne fungal pathogen that causes devastating wilt diseases in many crops. The discovery and identity of novel lncRNAs and their association with virulence may contribute to an increased understanding of the regulation of virulence in V. dahliae. Here, we identified a total of 352 lncRNAs in V. dahliae. The lncRNAs were transcribed from all V. dahliae chromosomes, typically with shorter open reading frames, lower GC content, and fewer exons than protein-coding genes. In addition, 308 protein-coding genes located within 10 kb upstream and 10 kb downstream of lncRNAs were identified as neighboring genes, and which were considered as potential targets of lncRNA. These neighboring genes encode products involved in development, stress responses, and pathogenicity of V. dahliae, such as transcription factors (TF), kinase, and members of the secretome. Furthermore, 47 lncRNAs were significantly differentially expressed in V. dahliae following inoculation of susceptible cotton (Gossyoiumhisutum) cultivar Junmian No.1, suggesting that lncRNAs may be involved in the regulation of virulence in V. dahliae. Moreover, correlations in expression patterns between lncRNA and their neighboring genes were detected. Expression of lncRNA012077 and its neighboring gene was up-regulated 6 h following inoculation of cotton, while the expression of lncRNA007722 was down-regulated at 6 h but up-regulated at 24 h, in a pattern opposite to that of its neighboring gene. Overexpression of lncRNA012077 in wild-type strain (Vd991) enhanced its virulence on cotton while overexpression of lncRNA009491 reduced virulence. Identification of novel lncRNAs and their association with virulence may provide new targets for disease control.


Assuntos
Gossypium/microbiologia , Doenças das Plantas/microbiologia , RNA Longo não Codificante , Verticillium , Resistência à Doença , RNA Longo não Codificante/genética , Verticillium/genética , Verticillium/patogenicidade
13.
Insect Biochem Mol Biol ; 141: 103708, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34973420

RESUMO

Sex pheromones facilitate species-specific sex communication within the Lepidoptera. They are detected by specialised pheromone receptors (PRs), most of which to date fall into a single monophyletic receptor lineage (frequently referred to as "the PR clade") within the odorant receptor (OR) family. Here we investigated PRs of the invasive horticultural pest, Epiphyas postvittana, commonly known as the light brown apple moth. Ten candidate PRs were selected, based on their male-biased expression in antennae or their relationship to the PR clade, for functional assessment in both HEK293 cells and Xenopus oocytes. Of these, six ORs responded to compounds that include components of the E. postvittana ('Epos') sex pheromone blend or compounds that antagonise sex pheromone attraction. In phylogenies, four of the characterised receptors (EposOR1, 6, 7 and 45) fall within the PR clade and two other male-biased receptors (EposOR30 and 34) group together well outside the PR clade. This new clade of pheromone receptors includes the receptor for (E)-11-tetradecenyl acetate (EposOR30), which is the main component of the sex pheromone blend for this species. Interestingly, receptors of the two clades do not segregate by preference for compounds associated with behavioural response (agonist or antagonist), isomer type (E or Z) or functional group (alcohol or acetate), with examples of each scattered across both clades. Phylogenetic comparison with PRs from other species supports the existence of a second major clade of lepidopteran ORs including, EposOR30 and 34, that has been co-opted into sex pheromone detection in the Lepidoptera. This second clade of sex pheromone receptors has an origin that likely predates the split between the major lepidopteran families.


Assuntos
Mariposas/genética , Receptores de Feromônios/genética , Atrativos Sexuais/genética , Animais , Feminino , Células HEK293 , Humanos , Masculino , Filogenia , Receptores de Feromônios/classificação
14.
Am J Physiol Renal Physiol ; 322(1): F55-F67, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843409

RESUMO

We used whole cell recording to examine the renal outer medullary K+ channel (ROMK or Kir1.1) and epithelial Na+ channel (ENaC) in the late distal convoluted tubule (DCT2)/initial connecting tubule (iCNT) and in the cortical collecting duct (CCD) of kidney tubule-specific neural precursor cell-expressed developmentally downregulated protein 4-2 (Nedd4-2) knockout mice (Ks-Nedd4-2 KO) and floxed neural precursor cell-expressed developmentally downregulated 4-like (Nedd4l) mice (control). Tertiapin Q (TPNQ)-sensitive K+ currents (ROMK) were smaller in both the DCT2/iCNT and CCD of Ks-Nedd4-2 KO mice on a normal diet than in control mice. Neither high dietary salt intake nor low dietary salt intake had a significant effect on ROMK activity in the DCT2/iCNT and CCD of control and Ks-Nedd4-2 KO mice. In contrast, high dietary K+ intake (HK) increased, whereas low dietary K+ intake (LK) decreased TPNQ-sensitive K+ currents in floxed Nedd4l mice. However, the effects of dietary K+ intake on ROMK channel activity were absent in Ks-Nedd4-2 KO mice since neither HK nor LK significantly affected TPNQ-sensitive K+ currents in the DCT2/iCNT and CCD. Moreover, TPNQ-sensitive K+ currents in the DCT2/iCNT and CCD of Ks-Nedd4-2 KO mice on HK were similar to those of control mice on LK. Amiloride-sensitive Na+ currents in the DCT2/iCNT and CCD were significantly higher in Ks-Nedd4-2 KO mice than in floxed Nedd4l mice on a normal K+ diet. HK increased ENaC activity of the DCT2/iCNT only in control mice, but HK stimulated ENaC of the CCD in both control and Ks-Nedd4-2 KO mice. Moreover, the HK-induced increase in amiloride-sensitive Na+ currents was larger in Ks-Nedd4-2 KO mice than in control mice. Deletion of Nedd4-2 increased with no lysine kinase 1 expression and abolished HK-induced inhibition of with no lysine kinase 1. We conclude that deletion of Nedd4-2 increases ENaC activity but decreases ROMK activity in the aldosterone-sensitive distal nephron and that HK fails to stimulate ROMK, but robustly increases ENaC activity in the CCD of Nedd4-2-deficient mice.NEW & NOTEWORTHY We demonstrate that renal outer medullary K+ (ROMK) channel activity is inhibited in the late distal convoluted tubule/initial connecting tubule and cortical collecting duct of neural precursor cell-expressed developmentally downregulated protein 4-2 (Nedd4-2)-deficient mice. Also, deletion of Nedd4-2 abolishes the stimulatory effect of dietary K+ intake on ROMK. The lack of high K+-induced stimulation of ROMK is associated with the absence of high K+-induced inhibition of with no lysine kinase 1.


Assuntos
Aldosterona/farmacologia , Túbulos Renais Distais/efeitos dos fármacos , Ubiquitina-Proteína Ligases Nedd4/deficiência , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Potássio na Dieta/metabolismo , Animais , Dieta Hipossódica , Canais Epiteliais de Sódio/metabolismo , Túbulos Renais Distais/metabolismo , Masculino , Potenciais da Membrana , Camundongos Knockout , Ubiquitina-Proteína Ligases Nedd4/genética , Cloreto de Sódio na Dieta/metabolismo
16.
Insects ; 12(12)2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34940155

RESUMO

It remains a conundrum in the evolution of sexual communication how the signals and responses can co-ordinate the changes during speciation. The genus Ostrinia contains several closely related species as well as distinctive strains with pheromone polymorphism and represents an example of ongoing speciation. Extensive studies in the genus, especially in the species the European corn borer O. nubilalis (ECB), the Asian corn borer O. furnacalis (ACB) and the adzuki bean borer O. scapulalis (ABB), have provided valuable insights into the evolution of sex pheromone communication. This review presents a comprehensive overview of the research on pheromone communication in different Ostrinia species over the past four decades, including pheromone identification and biosynthesis, the ligand profiles of pheromone receptor (PR) genes, the physiology of peripheral olfactory sensory neurons (OSNs) and the projection pattern to the antennal lobe. By integrating and comparing the closely related Ostrinia species and strains, it provides an evolutionary perspective on the sex pheromone communication in moths in general and also outlines the outstanding questions that await to be elucidated by future studies.

17.
Chin J Nat Med ; 19(12): 881-899, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34961587

RESUMO

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Acidente Vascular Cerebral , Animais , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Acidente Vascular Cerebral/tratamento farmacológico
18.
Microbiol Spectr ; 9(3): e0111821, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34937170

RESUMO

Verticillium dahliae is a widespread soilborne fungus that causes Verticillium wilt on numerous economically important plant species. In tomato, until now, three races have been characterized based on the response of differential cultivars to V. dahliae, but the genetic basis of race divergence in V. dahliae remains undetermined. To investigate the genetic basis of race divergence, we sequenced the genomes of two race 2 strains and four race 3 strains for comparative analyses with two known race 1 genomes. The genetic basis of race divergence was described by the pathogenicity-related genes among the three races, orthologue analyses, and genomic structural variations. Global comparative genomics showed that chromosomal rearrangements are not the only source of race divergence and that race 3 should be split into two genotypes based on orthologue clustering. Lineage-specific regions (LSRs), frequently observed between genomes of the three races, encode several predicted secreted proteins that potentially function as suppressors of immunity triggered by known effectors. These likely contribute to the virulence of the three races. Two genes in particular that can act as markers for race 2 and race 3 (VdR2e and VdR3e, respectively) contribute to virulence on tomato, and the latter acts as an avirulence factor of race 3. We elucidated the genetic basis of race divergence through global comparative genomics and identified secreted proteins in LSRs that could potentially play critical roles in the differential virulence among the races in V. dahliae. IMPORTANCE Deciphering the gene-for-gene relationships during host-pathogen interactions is the basis of modern plant resistance breeding. In the Verticillium dahliae-tomato pathosystem, two races (races 1 and 2) and their corresponding avirulence (Avr) genes have been identified, but strains that lack these two Avr genes exist in nature. In this system, race 3 has been described, but the corresponding Avr gene has not been identified. We de novo-sequenced genomes of six strains and identified secreted proteins within the lineage-specific regions (LSRs) distributed among the genomes of the three races that could potentially function as manipulators of host immunity. One of the LSR genes, VdR3e, was confirmed as the Avr gene for race 3. The results indicate that differences in transcriptional regulation may contribute to race differentiation. This is the first study to describe these differences and elucidate roles of secreted proteins in LSRs that play roles in race differentiation.


Assuntos
Ascomicetos/classificação , Ascomicetos/genética , Genoma Fúngico/genética , Lycopersicon esculentum/microbiologia , Resistência à Doença/genética , Genômica , Genótipo , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/microbiologia , Microbiologia do Solo , Transcrição Genética/genética , Virulência/genética
20.
Int J Mol Sci ; 22(21)2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34769506

RESUMO

Plants serve as a niche for the growth and proliferation of a diversity of microorganisms. Soil microorganisms, which closely interact with plants, are increasingly being recognized as factors important to plant health. In this study, we explored the use of high-throughput DNA sequencing of the fungal ITS and bacterial 16S for characterization of the fungal and bacterial microbiomes following biocontrol treatment (DT) with Bacillus subtilis strain Bv17 relative to treatments without biocontrol (DC) during the potato growth cycle at three time points. A total of 5631 operational taxonomic units (OTUs) were identified from the 16S data, and 2236 OTUs were identified from the ITS data. The number of bacterial and fungal OTU in DT was higher than in DC and gradually increased during potato growth. In addition, indices such as Ace, Chao, Shannon, and Simpson were higher in DT than in DC, indicating greater richness and community diversity in soil following the biocontrol treatment. Additionally, the potato tuber yields improved without a measurable change in the bacterial communities following the B. subtilis strain Bv17 treatment. These results suggest that soil microbial communities in the rhizosphere are differentially affected by the biocontrol treatment while improving potato yield, providing a strong basis for biocontrol utilization in crop production.


Assuntos
Bacillus subtilis/fisiologia , Fungos/fisiologia , Tubérculos/crescimento & desenvolvimento , Microbiologia do Solo/normas , Solanum tuberosum/crescimento & desenvolvimento , Biodiversidade , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Microbiota , Tubérculos/genética , Tubérculos/microbiologia , Rizosfera , Solanum tuberosum/genética , Solanum tuberosum/microbiologia
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