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1.
Sensors (Basel) ; 24(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39000995

RESUMEN

A reliable and efficient rail track defect detection system is essential for maintaining rail track integrity and avoiding safety hazards and financial losses. Eddy current (EC) testing is a non-destructive technique that can be employed for this purpose. The trade-off between spatial resolution and lift-off should be carefully considered in practical applications to distinguish closely spaced cracks such as those caused by rolling contact fatigue (RCF). A multi-channel eddy current sensor array has been developed to detect defects on rails. Based on the sensor scanning data, defect reconstruction along the rails is achieved using an inverse algorithm that includes both direct and iterative approaches. In experimental evaluations, the EC system with the developed sensor is used to measure defects on a standard test piece of rail with a probe lift-off of 4-6 mm. The reconstruction results clearly reveal cracks at various depths and spacings on the test piece.

2.
Poult Sci ; 103(6): 103770, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38652955

RESUMEN

Alpiniae oxyphylla fructus was extensively utilized both as dietary supplements and traditional herbal medicines for healthcare functions and has exhibited a positive impact on animal health. The present study aimed to investigate the effects of Alpiniae oxyphyllae fructus powder (AOP) on production performance, egg quality, egg yolk fatty acid composition, reproductive hormones, antioxidant capacity, immunity, anti-apoptosis ability, and intestinal health in hens. A total of 252 Hainan Wenchang laying hens (30-wk-old) were randomly divided into 3 groups with 6 replicates, a basic diet with 0 (CON), 1 g/kg AOP (AOP1), and 3 g/kg (AOP3) mixed AOP. The AOP supplementation was found to decrease the feed conversion ratio and embryo mortality but to increase the laying rate, average egg weight, and oviduct index linearly (p < 0.05). Furthermore, AOP treatment reduced the total saturated fatty acids and palmitic acid (C16:0) in the egg yolk while increasing eggshell strength, albumen height, and Haugh unit (p < 0.05). The serum levels of albumin and phosphorus were increased, whereas total cholesterol, triglycerides, and glucose levels decreased as a result of AOP treatment (p < 0.05). The inclusion of 3 g/kg AOP had higher 17 ß-estradiol and follicle-stimulating hormone levels in serum, while it up-regulated follicle-stimulating hormone receptor and gonadotropin-releasing hormone expression in ovary (p < 0.05). Dietary AOP strengthened the expression of nuclear factor erythroid2-related factor 2 in ovary and increased the activity of superoxide dismutase and total antioxidant capacity, but had a lower malondialdehyde content in serum (p < 0.05). AOP at 3 g/kg up-regulated superoxide dismutase 1 and heme oxygenase 1 expression in jejunum and ovary (p < 0.05). Meanwhile, AOP supplementation down-regulated p53 expression in ovary and bcl-2-associated x expression in liver and jejunum, especially 3 g/kg of AOP had lower caspase-8 concentrations and down-regulated bcl-2-associated x and caspase-3 expression in ovary (p < 0.05). AOP treatment increased serum levels of immunoglobulin A and immunoglobulin M and upregulated interleukin-4 expression in the liver, while decreasing interleukin-1ß expression in liver and ovary and nod-like receptor protein 3 expression in jejunum (p < 0.05). Dietary AOP increased the ratio of villus height to crypt depth but decreased crypt depth in jejunum, especially when 1 g/kg AOP increased expression levels of occludin, mucin-2, peptide-transporter 1, and sodium glucose cotransporter 1 in jejunum (p < 0.05). AOP treatment altered the composition of the cecal microbial community, as evidenced by increased abundance of Oscillospira and Phascolarctobacterium and reduced richness of Clostridiaceae_Clostridium. Dietary AOP supplementation enriched lipid, amino acid, and propanoate metabolism. Spearman's correlation analysis revealed that the genera Oscillospira, Blautia, and Megasphaera were related to laying performance and intestinal integrity. In brief, supplementation of AOP, especially at 3 g/kg, could improve production performance and egg quality of hens via modulating reproductive hormones, antioxidant capacity, immunity, intestinal barrier, and cecal microbiota. Overall, the present work recommends the dietary inclusion of AOP as a beneficial additive for improving the performance of hens.


Asunto(s)
Alimentación Animal , Antioxidantes , Pollos , Dieta , Suplementos Dietéticos , Animales , Pollos/fisiología , Pollos/inmunología , Femenino , Alimentación Animal/análisis , Dieta/veterinaria , Suplementos Dietéticos/análisis , Antioxidantes/metabolismo , Distribución Aleatoria , Alpinia/química , Intestinos/efectos de los fármacos , Intestinos/fisiología , Frutas/química , Óvulo/efectos de los fármacos , Óvulo/fisiología , Óvulo/química , Yema de Huevo/química , Reproducción/efectos de los fármacos , Relación Dosis-Respuesta a Droga
3.
Poult Sci ; 103(1): 103201, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37980727

RESUMEN

Chinese herbs have been used as feed additives and are commonly utilized in domestic intensive livestock farming. However, their impact on the production performance and intestinal health of broiler breeders has yet to be thoroughly explored. This study aimed to evaluate the effects of a Chinese herbal mixture (CHM) on the production performance of broiler breeders in terms of reproductive hormones, antioxidant capacity, immunity, and intestinal health of broiler breeders. A total of 336 thirty-wk-old hens were randomly allotted to 4 groups with 6 replicates of fourteen hens each, which fed a basal diet supplemented with 0 (CON), 500 (CHM500), 1,000 (CHM1000), and 1,500 (CHM1500) mg/kg CHM for 56 days, respectively. Our results showed that dietary supplementation with CHM1000 increased the laying rate and number of SYF and decreased the feed conversion ratio (P < 0.05). All CHM groups increased oviduct and ovarian indexes, serum E2 and T-AOC levels, and decreased serum TG and MDA levels compared with CON (P < 0.05). In comparison to the CON group, the CHM1000 and CHM1500 groups increased serum ALB, IgM, and IL-10 levels, whereas the CHM1000 group also increased serum TP and SOD levels, and the CHM1500 group increased serum P and decreased serum TNF-α (P < 0.05). The addition of CHM increased FSHR expressions in the ovary, Claudin-1 expressions in the jejunum, and SOD1 expressions in the liver and ovary, but decreased the mRNA expressions of INH in the ovary as well as IL-2 and IL-6 expressions in the jejunum (P < 0.05). Moreover, CHM500 and CHM1000 groups increased CAT, GPx, and HO-1 expression in the ovary, and SOD1 and GPx expression in the jejunum, while decreasing IL-17A expression in the jejunum (P < 0.05). In addition, CHM1000 and CHM1500 groups increased villus height, VCR, and the mRNA expressions of Nrf2, HO-1, Occludin, and MUC2 in the jejunum, and IL-10 expression in the ovary, while decreasing IL-2 and IL-17A expression in the ovary, in addition to increasing GPx, Nrf2, HO-1, NQO1, and IL-10 expression in the liver (P < 0.05). Supplementation with CHM1000 increased ESR-α, ESR-ß, GnRH, Nrf2, and NQO1 expression in the ovary, but decreased IFN-γ expression in the ovary as well as crypt depth in the jejunum (P < 0.05). Supplementing CHM1500 increased NQO1 and ZO-1 expression in the jejunum and decreased IL-2 in the liver (P < 0.05). The high-throughput sequencing results showed that dietary CHM1000 supplementation altered the composition of the intestinal microbiota, as evidenced by the regulation of the genera Lactobacillus, Faecalibacterium, and Phascolarctobacterium. PICRUSt analysis revealed that metabolic pathways of bacterial chemotaxis, butanoate metabolism, and synthesis and degradation of ketone bodies were enriched in the CHM1000 group. Spearman's correlation analysis indicated that the differentiated genera were significantly associated with the production performance, serum hormone, and gut barrier-related genes. Taken together, supplementation of CHM, especially at 1,000 mg/kg, could improve production performance by regulating reproductive hormones, antioxidant capacity, immunity, and intestinal health of broiler breeders, and maybe provide insights into its application as a potential feed additive to promote the performance of broiler breeders.


Asunto(s)
Antioxidantes , Interleucina-10 , Animales , Femenino , Antioxidantes/metabolismo , Interleucina-17 , Pollos/fisiología , Factor 2 Relacionado con NF-E2/metabolismo , Interleucina-2 , Superóxido Dismutasa-1/metabolismo , Suplementos Dietéticos/análisis , Dieta/veterinaria , Hormonas/metabolismo , ARN Mensajero/metabolismo , Alimentación Animal/análisis
4.
Animals (Basel) ; 13(22)2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-38003204

RESUMEN

The aim of this study was to investigate the effects of adding perilla seed meal (PSM) to the diet on reproductive performance, egg quality, yolk fatty acids, antioxidant capacity and liver lipid metabolism in breeding hens. A total of 192 31-week-old yellow-feathered hens were randomly divided into 4 treatments with 6 replicates of 8 birds for 8 weeks. The chickens were fed a typical corn-soybean meal diet containing 0% (control), 0.3%, 0.6%, and 1% PSM. The results showed that PSM can change the productivity of laying hens. Adding 0.6% PSM to the feed reduced the mortality rate of chickens. Adding 1% PSM improved the fertilization rate and hatching rate of chickens. Regarding egg quality, the albumen height and Haugh unit were improved in the 0.6% PSM group. The content of MUFAs and PUFAs in the egg yolk was increased in all the PSM groups, while SFAs were only increased in the 0.6% PSM group. Among the indicators related to lipid metabolism, serum GLU decreased in all the PSM groups. The 0.6% PSM group had a reduction in serum and liver TG, as well as reductions in serum LDL-C and ALT. The same results were observed for the abdominal fat percentage in the 0.6% PSM group. Liver lipid metabolism-associated gene expression of FAS and LXRα was decreased in all the PSM groups, and the mRNA expression of ACC and SREBP-1c was significantly reduced in the 0.6% PSM group. HE staining showed that the vacuoles in the liver tissue gradually decreased with increasing PSM doses, especially the 1% PSM dose. Lipid droplets with a similar trend were observed using Oil Red O staining. In the results of the antioxidant capacity test, the serum T-AOC was increased in the 0.6% and 1% PSM groups, and the SOD in both the serum and liver was significantly increased in all the PSM groups. The expression of antioxidant-related genes such as Nrf2, NQO-1, HO-1, CAT and GSH-Px was significantly upregulated in the 1% PSM group. In conclusion, the PSM diet improved the lipid metabolism and antioxidant capacity of breeding hens. PSM reduces mortality and improves fertilization and hatchability in the late laying period of chickens, resulting in greater benefits. We recommend adding 0.6% PSM to layer feed, which improves the physical condition of the hens and brings higher economic benefits.

5.
Genes Dis ; 10(5): 2049-2063, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37492705

RESUMEN

In Pseudomonas aeruginosa (P. aeruginosa), transcription factors (TFs) are important mediators in the genetic regulation of adaptability and pathogenicity to respond to multiple environmental stresses and host defences. The P. aeruginosa genome harbours 371 putative TFs; of these, about 70 have been shown to regulate virulence-associated phenotypes by binding to the promoters of their target genes. Over the past three decades, several techniques have been applied to identify TF binding sites on the P. aeruginosa genome, and an atlas of TF binding patterns has been mapped. The virulence-associated regulons of TFs show complex crosstalk in P. aeruginosa's regulatory network. In this review, we summarise the recent literature on TF regulatory networks involved in the quorum-sensing system, biofilm formation, pyocyanin synthesis, motility, the type III secretion system, the type VI secretion system, and oxidative stress responses. We discuss future perspectives that could provide insights and targets for preventing clinical infections caused by P. aeruginosa based on the global regulatory network of transcriptional regulators.

6.
Poult Sci ; 102(7): 102714, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37172360

RESUMEN

This study aimed to investigate the effects of polyherbal mixtures (PHM) on growth performance, antioxidant capacities, immune function, and intestinal health in yellow-feathered broilers. PHM is composed of five traditional Chinese medicine herbs (Portulaca oleracea L., Radix Sophora flavescens, Thalictrum glandulosissimum, Terra flava usta, and Pogostemon cablin). A total of 270 one-day-old yellow-feathered broilers were randomly allotted into 3 treatments for a 42-d feeding trial, each with 6 replicates of 15 birds. The dietary treatments consisted of a basal diet (CON), a basal diet supplemented with 50 mg/kg chlortetracycline (CTC), and a basal diet supplemented with 1000 mg/kg PHM. The results showed that dietary PHM supplementation increased body weight, ADG, and decreased F/G compared to the CON. PHM also increased spleen index and mRNA expression of IL-4 (d 21), and thymus index, serum IgA (d 42) and IgG, IL-4 and sIgA in jejunal mucosa (d 21 and 42), but decreased serum IFN-γ and mRNA expression of IFN-γ (d 21 and 42). In addition, PHM increased serum SOD, GSH-Px (d 21 and 42) and T-AOC (d 42), but decreased the content of serum MDA (d 21), the up-regulated mRNA expression of GSH-Px, CAT (d 21), SOD and CAT (d 42). Furthermore, PHM also improved the intestinal epithelial barrier indicators by the up-regulated mRNA expression of CLDN-1, OCLN (d 21 and 42) and ZO-1 (d 21), and the increased of villus height and villus height to crypt depth in jejunum (d 42). The high-throughput sequencing results showed that dietary PHM supplementation increased the alpha diversity and relative abundance of Oscillospira and Ruminococcus (d 21) and Lactobacillus (d 42), whereas decreasing that of Enterococcus (d 21) compared with CON. PICRUSt analysis revealed that metabolic pathways of carbohydrate, energy, lipid, cofactors, and vitamins were significantly enriched in the PHM group. Spearman's correlation analysis revealed that the genera Lactobacillus, Enterococcus, Ruminococcus, Oscillospira, and Faecalibacterium were related to growth performance, intestinal integrity, immune-related factors, antioxidant indices, and tight junction proteins. In conclusion, the results indicated that dietary PHM supplementation improved growth performance and immune status of yellow-feathered broilers by enhancing antioxidant capacities, barrier function, and modulated jejunal microbial communities. PHM used in our study has the potential to replace prophylactic antibiotic use in poultry production systems.


Asunto(s)
Antioxidantes , Pollos , Animales , Alimentación Animal/análisis , Antioxidantes/metabolismo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Inmunidad , Interleucina-4 , Yeyuno/metabolismo , ARN Mensajero , Superóxido Dismutasa
7.
STAR Protoc ; 4(2): 102322, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37210720

RESUMEN

Transcriptomic data and ChIP-seq data from bacteria are systematically analyzed and efficiently combined. We describe the software environment for analysis and the download and installation methods. Furthermore, we describe the analytical process and present the corresponding mini-test data, which can be conveniently restored and reproduced by users. Moreover, we provide the script for data consolidation, which allows multiple files to be rapidly merged. Overall, this protocol presents software parameters, R codes, and in-house Perl scripts for analyzing bacterial multi-omics data. For complete details on the use and execution of this protocol, please refer to Xin et al.

8.
Phytomedicine ; 110: 154645, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36634382

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder in gastrointestinal tract. Shen Ling Bai Zhu San (SLBZS), which has a long history of use in Traditional Chinese Medicine (TCM), has been widely used to treat gastrointestinal diseases. The isolated fractions of TCM have also been proved to possess an important potential for treating diseases, which are due to their effective components. PURPOSE: In this study, we examined the possibility that SLBZS and its isolated active fractions may prevent DSS-induced colitis, and investigated the potential mechanisms by regulating genetic profile of colon. METHODS: Colitis mice were induced by 2.5% DSS for 7 days, and then SLBZS and different SLBZS extracts were administrated to protect the mice for 7 days. Body weight, diarrhea, bleeding in stool, colon length, spleen weight, cytokines of serum and colon and pathology of colon were assessed. The level of Ginsenoside Rg1, Re and Rb1 in different SLBZS extracts and qualitative analysis of n-butanol extract of SLBZS (S-Nb) was performed by HPLC and LC-MS, respectively. And the effects of S-Nb on the transcriptome in colitis were investigated. RESULTS: Our results showed that SLBZS and S-Nb significantly regained body weight, reduced DAI, splenomegaly and the length of colon and attenuated histological damage of the colon. Meanwhile, SLBZS and S-Nb markedly reduced the levels of TNF-α, IL-1ß and IL-6 and increased the level of IL-10 in serum and colon. These effects may be associated with the high levels of Ginsenoside Rg1, Re and Rb1 and rich variety of compounds in S-Nb including 6 ginsenosides, glycyrrhizin, L-tryptophan, and so on. Transcriptome analysis revealed that S-Nb selectively regulated 103 differentially expressed genes (DEGs), 36 of which were changed in DSS-induced mice. And the genes of Per2, Per3, Npy and Serpina3m were closely related to colitis and also restored by S-Nb with different extent. Remarkably, these DEGs modulated the biological functions of colitis mice, including extracellular region, response to external stimulus, MAPK signaling pathway and arginine and proline metabolism. CONCLUSIONS: These data indicated that SLBZS and S-Nb blunted DSS-induced colitis by modulating differentially expression gene profile and biological functions based on their ginsenosides and rich compounds.


Asunto(s)
Colitis , Ginsenósidos , Ratones , Animales , Ginsenósidos/farmacología , 1-Butanol/farmacología , Butanoles/farmacología , Cromatografía Liquida , Espectrometría de Masas en Tándem , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/patología , Colon/patología , Enfermedad Crónica , Perfilación de la Expresión Génica , Peso Corporal , Sulfato de Dextran , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Citocinas
9.
Front Vet Sci ; 10: 1320469, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38162476

RESUMEN

This study aimed to evaluate the effects of Chinese herbal mixtures (CHMs) on productive performance, egg quality, immune status, anti-apoptosis ability, caecal microbiota, and offspring meconial microbiota in hens. A total of 168 thirty-week-old Wenchang breeder hens were randomly divided into two groups, with each group comprising six replicate pens of fourteen hens. The groups were fed a basal diet (CON group) and a basal diet with 1,000 mg/kg CHMs (CHMs group) for 10 weeks. Our results showed that dietary supplementation with CHMs increased the laying rate, average egg weight, hatch of fertile, and offspring chicks' weight while concurrently reducing the feed conversion ratio (FCR) and embryo mortality (p < 0.05). The addition of CHMs resulted in significant improvements in various egg quality parameters, including eggshell strength, albumen height, haugh unit, and the content of docosatetraenoic acid (C20:4n-6) in egg yolk (p < 0.05). The supplementation of CHMs had a greater concentration of IgA and IgG while decreasing the content of IL-6 in serum compared with the CON group (p < 0.05). Addition of CHMs to the diet increased the expression of Bcl-2 and IL-4 in liver and ovary, decreased the expression of IL-1ß, Bax, and Caspase-8 in jejunum and ovary, and decreased the expression of NF-κB in liver, jejunum, and ovary (p < 0.05). Moreover, dietary CHMs reduced the abundance of Desulfovibrio in caecal microbiota as well as decreased the abundance of Staphylococcaceae_Staphylococcus and Pseudomonadaceae_Pseudomonas in the offspring meconial microbiota (p < 0.05). In conclusion, the CHMs could improve productive parameters by enhancing immune status, anti-apoptosis capacity, and modulating the caecal microbiota of Wenchang breeder hens, as well as maintaining the intestinal health of the offspring chicks.

10.
Cell Rep ; 41(3): 111502, 2022 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-36261023

RESUMEN

Two-component systems (TCSs) consist of the biggest group of signal transduction pathways in biology. Although TCSs play key roles in sensing signals to sustain survival and virulence, the genome-wide regulatory variability and conservation and synergistic actions of global TCSs in response to external stimulus are still uncharacterized. Here, we integrate 120 transcriptome sequencing datasets and 38 chromatin immunoprecipitation sequencing datasets of the model phytopathogen Pseudomonas syringae to illustrate how bacterial TCSs dynamically govern their regulatory roles under changing environments. We reveal themes of conservation and variability in bacterial gene regulations in response to changing environments by developing a network-based PSTCSome (Pseudomonas syringae TCS regulome) containing 232 and 297 functional genes under King's B medium and minimal medium conditions, respectively. We identify 7 TCSs regulating the type III secretion system, motility, or exopolysaccharide production. Overall, this study represents an important source to study the plasticity of TCSs among other TCS-containing organisms.


Asunto(s)
Proteínas Bacterianas , Sistemas de Secreción Tipo III , Sistemas de Secreción Tipo III/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Virulencia/genética , Transducción de Señal/fisiología , Bacterias/metabolismo , Pseudomonas syringae/genética , Pseudomonas syringae/metabolismo
11.
EMBO Rep ; 22(12): e52805, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-34580996

RESUMEN

Bacteria use a variety of mechanisms, such as two-component regulatory systems (TCSs), to rapidly sense and respond to distinct conditions and signals in their host organisms. For example, a type III secretion system (T3SS) is a key determinant of the virulence of the model plant pathogen Pseudomonas syringae and contains the TCS RhpRS as a key regulator. However, the plant-derived compound targeting RhpRS remains unknown. Here, we report that RhpRS directly interacts with polyphenols and responds by switching off P. syringae T3SS via crosstalk with alternative histidine kinases. We identify three natural polyphenols that induce the expression of the rhpRS operon in an RhpS-dependent manner. The presence of these three specific polyphenols inhibits the phosphatase activity of RhpS, thus suppressing T3SS activation in T3SS-inducing conditions. The Pro40 residue of RhpS is essential to respond to these polyphenols. In addition, three non-cognate histidine kinases cooperatively phosphorylate RhpR and antagonize the rhpS mutant phenotype. This work illustrates that plant polyphenols can directly target P. syringae RhpRS, which results in bacterial virulence being switched off via a phosphorylation-related crosstalk.


Asunto(s)
Polifenoles , Pseudomonas syringae , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Enfermedades de las Plantas/microbiología , Polifenoles/metabolismo , Polifenoles/farmacología , Pseudomonas syringae/metabolismo , Virulencia
12.
Cell Rep ; 34(13): 108920, 2021 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-33789108

RESUMEN

Pseudomonas syringae, a Gram-negative plant pathogen, expresses multitudinous transcriptional regulators to control the type III secretion system (T3SS) and response to diverse environmental challenges. Although the mechanisms of virulence-associated regulators of P. syringae have been studied for decades, the overall crosstalk underlying these regulators is still elusive. Here, we identify five T3SS regulators (EnvZ-OmpR, CbrAB2, PhoPQ, PilRS, and MgrA), and find that the two-component systems EnvZ-OmpR and CbrAB2 negatively regulate the T3SS. To elucidate crosstalk between 16 virulence-associated regulators in P. syringae, we map an online intricate network called "PSRnet" (Pseudomonas syringae regulatory network) by combining the differentially expressed genes (DEGs) of these 16 regulators by RNA sequencing (RNA-seq) and their binding loci by chromatin immunoprecipitation sequencing (ChIP-seq). Consequently, we identify 238 and 153 functional genes involved in the T3SS and other virulence-related pathways in KB and MM media, respectively. Our results provide insights into the mechanism of plant infections caused by P. syringae.


Asunto(s)
Regulación Bacteriana de la Expresión Génica , Redes Reguladoras de Genes , Pseudomonas syringae/genética , Pseudomonas syringae/patogenicidad , Ácido Algínico/metabolismo , Proteínas Bacterianas/metabolismo , Genes Bacterianos , Movimiento , Oxidación-Reducción , Unión Proteica , Transcriptoma/genética , Sistemas de Secreción Tipo III/metabolismo , Virulencia/genética
13.
Expert Opin Drug Discov ; 15(12): 1403-1423, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32880507

RESUMEN

INTRODUCTION: Persistent infections caused by the superbug Pseudomonas aeruginosa and its resistance to multiple antimicrobial agents are huge threats to patients with cystic fibrosis as well as those with compromised immune systems. Multidrug-resistant P. aeruginosa has posed a major challenge to conventional antibiotics and therapeutic approaches, which show limited efficacy and cause serious side effects. The public demand for new antibiotics is enormous; yet, drug development pipelines have started to run dry with limited targets available for inventing new antibacterial drugs. Consequently, it is important to uncover potential therapeutic targets. AREAS COVERED: The authors review the current state of drug development strategies that are promising in terms of the development of novel and potent drugs to treat P. aeruginosa infection. EXPERT OPINION: The prevention of P. aeruginosa infection is increasingly challenging. Furthermore, targeting key virulence regulators has great potential for developing novel anti-P. aeruginosa drugs. Additional promising strategies include bacteriophage therapy, immunotherapies, and antimicrobial peptides. Additionally, the authors believe that in the coming years, the overall network of molecular regulatory mechanism of P. aeruginosa virulence will be fully elucidated, which will provide more novel and promising drug targets for treating P. aeruginosa infections.


Asunto(s)
Antibacterianos/farmacología , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Animales , Antibacterianos/efectos adversos , Desarrollo de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Humanos , Inmunoterapia , Terapia de Fagos/métodos , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/patogenicidad , Virulencia
14.
Environ Microbiol ; 22(7): 2968-2988, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32410332

RESUMEN

Lon, a member of the AAA+ protease family, plays vital roles in Type III secretion systems (T3SS), agglutination and colony shape in the model plant pathogen Pseudomonas syringae. Lon also functions as a transcriptional regulator in other bacterial species such as Escherichia coli and Brevibacillus thermoruber. To reveal the molecular mechanisms of Lon as a dual-function protein in P. syringae, we studied Lon-regulated genes by using RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq) and liquid chromatography-tandem mass spectrometry. As a transcriptional regulator, Lon directly regulated a group of genes (PSPPH_4788, gacA, fur, gntR, clpS, lon and glyA) and consequently regulated their functions, such as 1-dodecanol oxidation activity, motility, pyoverdine production, glucokinase activity, N-end rule pathway, lon expression and serine hydroxymethyltransferase activity. Mass spectrometry results revealed that the expression levels of five T3SS proteins (such as HrcV, HrpW1) were higher in the ∆lon strain than the wild-type (WT) strain in KB. In MM, 12 metabolic proteins (such as AcdS and NuoI) showed lower levels in the ∆lon strain than the WT strain. Taken together, these data demonstrate that the dual-function protein Lon sophisticatedly regulates virulence and metabolism in P. syringae.


Asunto(s)
Proteínas Bacterianas/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteasa La/metabolismo , Pseudomonas syringae/patogenicidad , Proteínas Bacterianas/genética , ADN/metabolismo , Regulación Bacteriana de la Expresión Génica/genética , Proteasa La/genética , Pseudomonas syringae/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Sistemas de Secreción Tipo III/metabolismo , Virulencia/genética
16.
Risk Anal ; 40(4): 842-857, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31943320

RESUMEN

The Europa mission approved in 2019 is still in the development phase. It is designed to conduct a detailed reconnaissance of that moon of Jupiter as it could possibly support life as we know it. This article is based on a top-down approach (mission → system → subsystems → components) to model the probability of mission failure. The focus here is on the case where the (uncertain) radiation load exceeds the (uncertain) capacity of critical subsystems of the spacecraft. The model is an illustrative quantification of the uncertainties about (1) the complex external radiation environment in repeated exposures, (2) the effectiveness of the shielding in different zones of the spacecraft, and (3) the components' capacities, by modeling all three as dynamic random variables. A simulation including a sensitivity analysis is used to obtain the failure probability of the whole mission in forty-five revolutions around Jupiter. This article illustrates how probabilistic risk analysis based on engineering models, test results and expert opinions can be used in the early stages of the design of space missions when uncertainties are large. It also describes the optimization of the spacecraft design, taking into account the decisionmakers' risk attitude and the mission resource constraints.


Asunto(s)
Radiación Cósmica , Probabilidad , Medición de Riesgo , Nave Espacial , Júpiter
17.
Nat Commun ; 10(1): 1190, 2019 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-30867414

RESUMEN

Understanding the Vitis species at the genomic level is important for cultivar improvement of grapevine. Here we report whole-genome genetic variation at single-base resolution of 472 Vitis accessions, which cover 48 out of 60 extant Vitis species from a wide geographic distribution. The variation helps to identify a recent dramatic expansion and contraction of effective population size in the domesticated grapevines and that cultivars from the pan-Black Sea region have a unique demographic history in comparison to the other domesticated cultivars. We also find selective sweeps for berry edibility and stress resistance improvement. Furthermore, we find associations between candidate genes and important agronomic traits, such as berry shape and aromatic compounds. These results demonstrate resource value of the resequencing data for illuminating the evolutionary biology of Vitis species and providing targets for grapevine genetic improvement.


Asunto(s)
Genoma de Planta/genética , Fitomejoramiento , Selección Genética/genética , Vitis/genética , Mar Negro , Domesticación , Europa (Continente) , Asia Oriental , Frutas/genética , Genotipo , Anotación de Secuencia Molecular , América del Norte , Filogenia , Filogeografía , Polimorfismo de Nucleótido Simple/genética , Secuenciación Completa del Genoma
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