ABSTRACT
Plant glycosyl hydrolases (GHs) play a crucial role in selectively breaking down carbohydrates and glycoconjugates during various cellular processes, such as reserve mobilization, pathogen defense, and modification/disassembly of the cell wall. In this study, we examined the distribution of GH genes in the Archaeplastida supergroup, which encompasses red algae, glaucophytes, and green plants. We identified that the GH repertoire expanded from a few tens of genes in early archaeplastidians to over 400 genes in modern angiosperms, spanning 40 GH families in land plants. Our findings reveal that major evolutionary transitions were accompanied by significant changes in the GH repertoire. Specifically, we identified at least 23 GH families acquired by green plants through multiple horizontal gene transfer events, primarily from bacteria and fungi. We found a significant shift in the subcellular localization of GH activity during green plant evolution, with a marked increase in extracellular-targeted GH proteins associated with the diversification of plant cell wall polysaccharides and defense mechanisms against pathogens. In conclusion, our study sheds light on the macroevolutionary processes that have shaped the GH repertoire in plants, highlighting the acquisition of GH families through horizontal transfer and the role of GHs in plant adaptation and defense mechanisms.
Subject(s)
Gene Transfer, Horizontal , Hydrolases , Humans , Phylogeny , Gene Transfer, Horizontal/genetics , Evolution, Molecular , Plants/geneticsABSTRACT
South American tomato leafminer, Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae), is native to South America, but is a major invasive and quarantine pest species in Europe, Africa, and Asia. It causes extensive damage of up to 100% yield loss in tomatoes (Solanum lycopersicum) in open and greenhouse conditions. Since its first invasion in Spain in 2006, it has spread rapidly into many countries in the Mediterranean and Western Europe and further invaded Africa and Asia. In Asia, it was first recorded in August 2009 in Turkey and spread to most South and East Asian countries. In this study, we reviewed existing work on the biology and distribution of T. absoluta in Asia, as well as the damage it causes. This review will help to develop efficient management tactics as well as establish quarantine and phytosanitary precautions in uninvaded countries.
Subject(s)
Lepidoptera , Moths , Solanum lycopersicum , Animals , Asia , South America , BiologyABSTRACT
BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.
Subject(s)
Cocaine-Related Disorders , Cocaine , Habenula , Humans , Cocaine-Related Disorders/therapy , Cocaine-Related Disorders/metabolism , Habenula/metabolism , Cocaine/pharmacology , Cocaine/metabolism , Neurons , Dopamine/metabolism , Dopamine/pharmacology , Hypothalamus/metabolismABSTRACT
BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.
Subject(s)
Humans , Cocaine/metabolism , Cocaine/pharmacology , Habenula/metabolism , Cocaine-Related Disorders/metabolism , Cocaine-Related Disorders/therapy , Dopamine/metabolism , Dopamine/pharmacology , Hypothalamus/metabolism , NeuronsABSTRACT
Pectobacterium brasiliense (P. brasiliense) is a necrotrophic bacterium that causes the soft rot disease in Brassica rapa. However, the mechanisms underlying plant immune responses against necrotrophic bacterial pathogens with a broad host range are still not well understood. Using a flg22-triggered seedling growth inhibition (SGI) assay with 455 Brassica rapa inbred lines, we selected six B. rapa flagellin-insensitive lines (Brfin2-7) and three B. rapa flagellin-sensitive lines (Brfs1-3). Brfin lines showed compromised flg22-induced immune responses (oxidative burst, mitogen-activated protein kinase (MAPK) activation, and seedling growth inhibition) compared to the control line R-o-18; nevertheless, they were resistant to P. brasiliense. To explain this, we analyzed the phytohormone content and found that most Brfin lines had higher P. brasiliense-induced jasmonic acid (JA) than Brfs lines. Moreover, MeJA pretreatment enhanced the resistance of B. rapa to P. brasiliense. To explain the correlation between the resistance of Brfin lines to P. brasiliense and activated JA signaling, we analyzed pathogen-induced glucosinolate (GS) content in B. rapa. Notably, in Brfin7, the neoglucobrassicin (NGBS) content among indole glucosinolates (IGS) was significantly higher than that in Brfs2 following P. brasiliense inoculation, and genes involved in IGSs biosynthesis were also highly expressed. Furthermore, almost all Brfin lines with high JA levels and resistance to P. brasiliense had higher P. brasiliense-induced NGBS levels than Brfs lines. Thus, our results show that activated JA-mediated signaling attenuates flg22-triggered immunity but enhances resistance to P. brasiliense by inducing indole glucosinolate biosynthesis in Brassica rapa. This study provides novel insights into the role of JA-mediated defense against necrotrophic bacterial pathogens within a broad host range.
ABSTRACT
Fanconi syndrome is a renal proximal tubulopathy characterized by excessive urinary loss of glucose, amino acids, several electrolytes, and bicarbonate. Here, we report the case of transient Fanconi syndrome in a dog following administration of firocoxib, cefadroxil, tramadol, and famotidine. A 10 mo old Maltese was presented with lethargy, anorexia, vomiting, and weight loss. Transient Fanconi syndrome without azotemia was associated with firocoxib, cefadroxil, tramadol, and famotidine treatment. The dog received supportive care including IV fluids, gastroprotectants, and oral nutritional supplements. Two months after initial diagnosis and treatment, the dog showed complete resolution of glucosuria and aminoaciduria. The unique features of Fanconi syndrome in this case emphasize the potential renal tubular toxicity of this widely used multiple-drug combination.
Subject(s)
4-Butyrolactone/analogs & derivatives , Cefadroxil/adverse effects , Dog Diseases/chemically induced , Famotidine/adverse effects , Fanconi Syndrome/veterinary , Sulfones/adverse effects , Tramadol/adverse effects , 4-Butyrolactone/administration & dosage , 4-Butyrolactone/adverse effects , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/adverse effects , Cefadroxil/administration & dosage , Dogs , Famotidine/administration & dosage , Fanconi Syndrome/chemically induced , Glucose , Glycosuria , Male , Sulfones/administration & dosage , Tramadol/administration & dosageABSTRACT
ABSTRACT Purpose The present study aimed to determine whether sarcopenia after radical cystectomy (RC) could predict overall survival (OS) in patients with urothelial bladder cancer (UBC). Materials and Methods The lumbar skeletal muscle index (SMI) of 80 patients was measured before and 1 year after RC. The prognostic significance of sarcopenia and SMI decrease after RC were evaluated using Kaplan-Meier analysis and a multivariable Cox regression model. Results Of 80 patients, 26 (32.5%) experienced sarcopenia before RC, whereas 40 (50.0%) experienced sarcopenia after RC. The median SMI change was -2.2 cm2/m2. Patients with sarcopenia after RC had a higher pathological T stage and tumor grade than patients without sarcopenia. Furthermore, the overall mortality rate was significantly higher in patients with sarcopenia than in those without sarcopenia 1 year after RC. The median follow-up time was 46.2 months, during which 22 patients died. Kaplan-Meier estimates showed a significant difference in OS rates based on sarcopenia (P=0.012) and SMI decrease (P=0.025). Multivariable Cox regression analysis showed that SMI decrease (≥2.2 cm2/m2) was an independent predictor of OS (hazard ratio: 2.68, confidence interval: 1.007-7.719, P = 0.048). Conclusions The decrease in SMI after surgery might be a negative prognostic factor for OS in patients who underwent RC to treat UBC.
Subject(s)
Humans , Male , Female , Aged , Urinary Bladder Neoplasms/surgery , Carcinoma in Situ/surgery , Cystectomy/adverse effects , Sarcopenia/etiology , Time Factors , Urinary Bladder Neoplasms/complications , Urinary Bladder Neoplasms/physiopathology , Urinary Bladder Neoplasms/mortality , Carcinoma in Situ/complications , Carcinoma in Situ/mortality , Body Mass Index , Cystectomy/methods , Cystectomy/mortality , Proportional Hazards Models , Multivariate Analysis , Retrospective Studies , Muscle, Skeletal/physiopathology , Kaplan-Meier Estimate , Sarcopenia/physiopathologyABSTRACT
PURPOSE: The present study aimed to determine whether sarcopenia after radical cystectomy (RC) could predict overall survival (OS) in patients with urothelial bladder cancer (UBC). MATERIALS AND METHODS: The lumbar skeletal muscle index (SMI) of 80 patients was measured before and 1 year after RC. The prognostic signifi cance of sarcopenia and SMI decrease after RC were evaluated using Kaplan-Meier analysis and a multivariable Cox regression model. RESULTS: Of 80 patients, 26 (32.5%) experienced sarcopenia before RC, whereas 40 (50.0%) experienced sarcopenia after RC. The median SMI change was -2.2 cm2/m2. Patients with sarcopenia after RC had a higher pathological T stage and tumor grade than patients without sarcopenia. Furthermore, the overall mortality rate was signifi - cantly higher in patients with sarcopenia than in those without sarcopenia 1 year after RC. The median follow-up time was 46.2 months, during which 22 patients died. Kaplan-Meier estimates showed a signifi cant difference in OS rates based on sarcopenia (P=0.012) and SMI decrease (P=0.025). Multivariable Cox regression analysis showed that SMI decrease (≥2.2 cm2/m2) was an independent predictor of OS (hazard ratio: 2.68, confi dence interval: 1.007-7.719, P = 0.048). CONCLUSIONS: The decrease in SMI after surgery might be a negative prognostic factor for OS in patients who underwent RC to treat UBC.
Subject(s)
Carcinoma in Situ/surgery , Cystectomy/adverse effects , Sarcopenia/etiology , Urinary Bladder Neoplasms/surgery , Aged , Body Mass Index , Carcinoma in Situ/complications , Carcinoma in Situ/mortality , Cystectomy/methods , Cystectomy/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Multivariate Analysis , Muscle, Skeletal/physiopathology , Proportional Hazards Models , Retrospective Studies , Sarcopenia/physiopathology , Time Factors , Urinary Bladder Neoplasms/complications , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/physiopathologyABSTRACT
Background: Rubus is an economically important fruit crop across the globe. Recently, several Rubus mutant genotypes with improved agronomic traits have been developed using gamma ray irradiation. This study investigated genetic diversity and variations in Rubus mutant genotypes using single nucleotide polymorphism (SNP) markers generated from genotyping-by-sequencing (GBS) analysis. A GBS library of 14 Rubus genotypes, consisting of seven boysenberry mutant lines, four blackberry mutant lines, and three original varieties, were sequenced on the Illumina Hiseq2000 platform. A set of SNPs were analyzed by Kompetitive Allele Specific PCR (KASP) assay in order to discriminate the Rubus genotypes. Results: A total of 50,831,040 (86.4%) reads of clean data were generated, and the trimmed length ranged from 116,380,840 to 509,806,521 bp, with an average of 228,087,333 bp per line. A total of 19,634 high-quality SNPs were detected, which contained 11,328 homozygous SNPs and 8306 heterozygous SNPs. A set of 1504 SNPs was used to perform a phylogenetic analysis, which showed that there were clear differences among the Rubus genotypes based on their origin. A total of 25 SNPs were used for the KASP assays, of which six KASP primer sets were successfully distinguished among the Rubus genotypes. Conclusions: This study demonstrated that the SNP and KASP method is an economically efficient tool for mutant screening in Rubus breeding programs.
Subject(s)
Polymorphism, Single Nucleotide/genetics , Rubus/genetics , Phylogeny , Breeding , Genetic Markers , Crops, Agricultural , Alleles , High-Throughput Nucleotide Sequencing , Gamma Rays , Genotype , MutationABSTRACT
BACKGROUND: Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay. RESULTS: Among 43 initially screened small molecule inhibitors of kinases that have no known anti-proliferative effect on VSMCs, a spleen tyrosine kinase (Syk) inhibitor (BAY61-3606) showed significant anti-proliferative effect on VSMCs. Further experiments indicated that BAY61 attenuated the VSMC proliferation in both concentration- and time-dependent manner, and it also significantly suppressed the migration of VSMCs as assessed by both wound healing assays and transwell assays. Additionally, BAY61 suppressed the sprouting of VSMCs from endothelium-removed aortic rings. CONCLUSION: The present study identified a Syk kinase inhibitor as a potent VSMC proliferation and migration inhibitor and warrants further studies to elucidate its underlying molecular mechanisms, such as its primary target, and to validate its in vivo efficacy as a therapeutic agent for restenosis and atherosclerosis.
Subject(s)
Cell Movement/drug effects , Cell Proliferation/drug effects , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , Niacinamide/analogs & derivatives , Pyrimidines/pharmacology , Syk Kinase/antagonists & inhibitors , Animals , Aorta, Thoracic/drug effects , Blotting, Western , Cell Migration Assays , Cells, Cultured , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Muscle, Smooth, Vascular/cytology , Niacinamide/pharmacology , Rats, Sprague-Dawley , Reproducibility of Results , Time Factors , Wound Healing/drug effectsABSTRACT
BACKGROUND: Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay. RESULTS: Among 43 initially screened small molecule inhibitors of kinases that have no known anti-proliferative effect on VSMCs, a spleen tyrosine kinase (Syk) inhibitor (BAY61-3606) showed significant anti-proliferative effect on VSMCs. Further experiments indicated that BAY61 attenuated the VSMC proliferation in both concentration- and time-dependent manner, and it also significantly suppressed the migration of VSMCs as assessed by both wound healing assays and transwell assays. Additionally, BAY61 suppressed the sprouting of VSMCs from endothelium-removed aortic rings. CONCLUSION: The present study identified a Syk kinase inhibitor as a potent VSMC proliferation and migration inhibitor and warrants further studies to elucidate its underlying molecular mechanisms, such as its primary target, and to validate its in vivo efficacy as a therapeutic agent for restenosis and atherosclerosis.
Subject(s)
Animals , Rats , Pyrimidines/pharmacology , Cell Movement/drug effects , Niacinamide/analogs & derivatives , Myocytes, Smooth Muscle/drug effects , Cell Proliferation/drug effects , Syk Kinase/antagonists & inhibitors , Muscle, Smooth, Vascular/drug effects , Aorta, Thoracic/drug effects , Time Factors , Wound Healing/drug effects , Cells, Cultured , Blotting, Western , Reproducibility of Results , Rats, Sprague-Dawley , Niacinamide/pharmacology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Cell Migration Assays , Muscle, Smooth, Vascular/cytologyABSTRACT
Candida albicans is the most common opportunistic fungal pathogen and causes local and systemic disease in immunocompromised patients. Alveolar macrophages (AMs) are pivotal for the clearance of C. albicans from the lung. Activated AMs secrete 5-lipoxygenase-derived leukotrienes (LTs), which in turn enhance phagocytosis and microbicidal activity against a diverse array of pathogens. Our aim was to investigate the role of LTB(4) and LTD(4) in AM antimicrobial functions against C. albicans and the signaling pathways involved. Pharmacologic and genetic inhibition of LT biosynthesis as well as receptor antagonism reduced phagocytosis of C. albicans when compared with untreated or WT controls. Conversely, exogenous LTs of both classes augmented base-line C. albicans phagocytosis by AMs. Although LTB(4) enhanced mainly mannose receptor-dependent fungal ingestion, LTD(4) enhanced mainly dectin-1 receptor-mediated phagocytosis. LT enhancement of yeast ingestion was dependent on protein kinase C-δ (PKCδ) and PI3K but not PKCα and MAPK activation. Both LTs reduced activation of cofilin-1, whereas they enhanced total cellular F-actin; however, LTB(4) accomplished this through the activation of LIM kinases (LIMKs) 1 and 2, whereas LTD(4) did so exclusively via LIMK-2. Finally, both exogenous LTB(4) and LTD(4) enhanced AM fungicidal activity in an NADPH oxidase-dependent manner. Our data identify LTB(4) and LTD(4) as key mediators of innate immunity against C. albicans, which act by both distinct and conserved signaling mechanisms to enhance multiple antimicrobial functions of AMs.
Subject(s)
Actins/metabolism , Candida albicans/metabolism , Candidiasis/metabolism , Cofilin 1/metabolism , Immunity, Innate/physiology , Leukotriene B4/metabolism , Macrophages, Alveolar/metabolism , Actins/genetics , Actins/immunology , Animals , Candida albicans/immunology , Candidiasis/genetics , Candidiasis/immunology , Cofilin 1/genetics , Cofilin 1/immunology , Enzyme Activation/genetics , Enzyme Activation/immunology , Extracellular Signal-Regulated MAP Kinases/genetics , Extracellular Signal-Regulated MAP Kinases/immunology , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Lectins, C-Type , Leukotriene B4/genetics , Leukotriene B4/immunology , Lim Kinases/genetics , Lim Kinases/immunology , Lim Kinases/metabolism , Macrophages, Alveolar/immunology , Membrane Proteins/genetics , Membrane Proteins/immunology , Membrane Proteins/metabolism , Mice , Mice, Knockout , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/immunology , Nerve Tissue Proteins/metabolism , Phagocytosis/genetics , Phagocytosis/immunology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/immunology , Phosphatidylinositol 3-Kinases/metabolism , Protein Kinase C-delta , Rats , Rats, WistarABSTRACT
This study was conducted to examine the in vitro activity of antimicrobials against Campylobacter spp. isolates from chicken and human sources and the genetic interrelation among them. During 2004-2008, a total of 173 Campylobacter spp. isolated from chicken meats (60 domestic and 62 imported chicken meats) and humans (n = 51) were tested for susceptibility to nine antimicrobials. Of 173 isolates, 140 (80.9%) showed multidrug resistance (MDR) against three to eight antimicrobials. The most frequent pattern type was MDR to four antimicrobials: ciprofloxacin, nalidixic acid, ampicillin, and tetracycline. Over 52.6% (91/173) of the isolates tested were resistant to these four antibiotics simultaneously. Especially, two and five isolates originated from Korea and Brazil showed resistance against all antibiotics tested, except for florfenicol. Further, 95% (57/60) of the isolates originated from domestic chicken showed resistance to ciprofloxacin, the antimicrobial agent of choice for treatment of human campylobacteriosis. Genotypic characterization of all Campylobacter isolates performed by pulsed-field gel electrophoresis yielded 74 types among the 173 isolates. Isolates sharing the same or similar genetic clusters were detected in different countries at different times. The pulsed-field gel electrophoresis patterns of chicken-related isolates were closely related to those of isolates from humans with gastroenteritidis. The results of this study suggest that MDR Campylobacter spp. are widespread and that Campylobacter with similar genotypes are circulating both in humans and in chicken meat in Korea.