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Background@#Human breast milk (HBM) contains optimal nutrients for infant growth.Probiotics are used to prevent disease and, when taken by the mother, they may affect infant microbiome as well as HBM. However, few studies have specifically investigated the effect of probiotic intake by the mother on HBM and infant microbiota at genus/species level. Therefore, we present a comprehensive analysis of paired HBM and infant feces (IF) microbiome samples before and after probiotic intake by HBM-producing mothers. @*Methods@#Lactating mothers were administered with Lactobacillus rhamnosus (n = 9) or Saccharomyces boulardii capsules (n = 9), for 2 months; or no probiotic (n = 7). Paired HBM and IF samples were collected before and after treatment and analyzed by next-generation sequencing. @*Results@#Forty-three HBM and 49 IF samples were collected and sequenced. Overall, in 43 HBM samples, 1,190 microbial species belonging to 684 genera, 245 families, 117 orders, and 56 classes were detected. In 49 IF samples, 372 microbial species belonging to 195 genera, 79 families, 42 orders, and 18 classes were identified. Eight of 20 most abundant genera in both HBM and IF samples overlapped: Streptococcus (14.42%), Lactobacillus, Staphylococcus, and Veillonella, which were highly abundant in the HBM samples; and Bifidobacterium (27.397%), Bacteroides, and Faecalibacterium, which were highly abundant in the IF samples. Several major bacterial genera and species were detected in the HBM and IF samples after probiotic treatment, illustrating complex changes in the microbiomes upon treatment. @*Conclusion@#This is the first Korean microbiome study in which the effect of different probiotic intake by the mother on the microbiota in HBM and IF samples was investigated.This study provides a cornerstone to further the understanding of the effect of probiotics on the mother and infant microbiomes.
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Background@#Human breast milk (HBM) contains optimal nutrients for infant growth.Probiotics are used to prevent disease and, when taken by the mother, they may affect infant microbiome as well as HBM. However, few studies have specifically investigated the effect of probiotic intake by the mother on HBM and infant microbiota at genus/species level. Therefore, we present a comprehensive analysis of paired HBM and infant feces (IF) microbiome samples before and after probiotic intake by HBM-producing mothers. @*Methods@#Lactating mothers were administered with Lactobacillus rhamnosus (n = 9) or Saccharomyces boulardii capsules (n = 9), for 2 months; or no probiotic (n = 7). Paired HBM and IF samples were collected before and after treatment and analyzed by next-generation sequencing. @*Results@#Forty-three HBM and 49 IF samples were collected and sequenced. Overall, in 43 HBM samples, 1,190 microbial species belonging to 684 genera, 245 families, 117 orders, and 56 classes were detected. In 49 IF samples, 372 microbial species belonging to 195 genera, 79 families, 42 orders, and 18 classes were identified. Eight of 20 most abundant genera in both HBM and IF samples overlapped: Streptococcus (14.42%), Lactobacillus, Staphylococcus, and Veillonella, which were highly abundant in the HBM samples; and Bifidobacterium (27.397%), Bacteroides, and Faecalibacterium, which were highly abundant in the IF samples. Several major bacterial genera and species were detected in the HBM and IF samples after probiotic treatment, illustrating complex changes in the microbiomes upon treatment. @*Conclusion@#This is the first Korean microbiome study in which the effect of different probiotic intake by the mother on the microbiota in HBM and IF samples was investigated.This study provides a cornerstone to further the understanding of the effect of probiotics on the mother and infant microbiomes.
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Scopulariopsis brevicaulis is a widely distributed soil fungus known as a common saprotroph of biodegradation. It is also an opportunistic human pathogen that can produce various secondary metabolites. Here, we report the first complete mitochondrial genome sequence of S. brevicaulis isolated from air in South Korea. Total length of the mitochondrial genome is 28,829 bp and encoded 42 genes (15 protein-coding genes, 2 rRNAs, and 25 tRNAs). Nucleotide sequence of coding region takes over 26.2%, and overall GC content is 27.6%. Phylogenetic trees present that S. brevicaulis is clustered with Lomentospora prolificans with presenting various mitochondrial genome length.
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Scopulariopsis brevicaulis is a widely distributed soil fungus known as a common saprotroph of biodegradation. It is also an opportunistic human pathogen that can produce various secondary metabolites. Here, we report the first complete mitochondrial genome sequence of S. brevicaulis isolated from air in South Korea. Total length of the mitochondrial genome is 28,829 bp and encoded 42 genes (15 protein-coding genes, 2 rRNAs, and 25 tRNAs). Nucleotide sequence of coding region takes over 26.2%, and overall GC content is 27.6%. Phylogenetic trees present that S. brevicaulis is clustered with Lomentospora prolificans with presenting various mitochondrial genome length.
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The root bark extract of Aralia taibaiensis is used traditionally for the treatment of diabetes mellitus in China. The total saponin extracted from Aralia Taibaiensis (sAT) has effective combined antihyperglycemic and hypolipidemic activities in experimental type 2 diabetic rats. However, the active compounds have not yet been fully investigated. In the present study, we examined effects of twelve triterpenoid saponins on AMP-activated protein kinase (AMPK) activation, and found that compound 28-O-β-D-glucopyranosyl ester (AT12) significantly increased phosphorylation of AMPK and Acetyl-CoA carboxylase (ACC). AT12 effectively decreased blood glucose, triglyceride (TG), free fatty acid (FFA) and low density lipoprotein-cholesterol (LDL-C) levels in the rat model of type 2 diabetes mellitus (T2DM). The mechanism by which AT12 activated AMPK was subsequently investigated. Intracellular ATP level and oxygen consumption were significantly reduced by AT12 treatment. The findings suggested AT12 was a novel AMPK activator, and could be useful for the treatment of metabolic diseases.
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Animales , Ratas , Acetil-CoA Carboxilasa , Adenosina Trifosfato , Proteínas Quinasas Activadas por AMP , Aralia , Glucemia , China , Diabetes Mellitus , Diabetes Mellitus Tipo 2 , Enfermedades Metabólicas , Modelos Animales , Consumo de Oxígeno , Fosforilación , Saponinas , TriglicéridosRESUMEN
Akt (also known as protein kinase B, PKB) has been seen to play a role in astrocyte activation of neuroprotection; however, the underlying mechanism on deregulation of Akt signaling in brain injuries is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following kainic acid (KA)-induced neurodegeneration of mouse hippocampus. In control mice, there was a weak signal for CTMP in the hippocampus, but CTMP was markedly increased in the astrocytes 3 days after KA treatment. To further investigate the effectiveness of Akt signaling, the phosphorylation of CTMP was examined. KA treatment induced an increased p-CTMP expression in the astrocytes of hippocampus at 1 day. LPS/IFN-γ-treatment on primary astrocytes promoted the p-CTMP was followed by phosphorylation of Akt and finally upregulation of CTMP and p-CREB. Time-dependent expression of p-CTMP, p-Akt, p-CREB, and CTMP indicate that LPS/IFN-γ-induced phosphorylation of CTMP can activate Akt/CREB signaling, whereas lately emerging enhancement of CTMP can inhibit it. These results suggest that elevation of CTMP in the astrocytes may suppress Akt activity and ultimately negatively affect the outcome of astrocyte activation (astroglisiois). Early time point enhancers of phosphorylation of CTMP and/or late time inhibitors specifically targeting CTMP may be beneficial in astrocyte activation for neuroprotection within treatment in neuroinflammatory conditions.
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Animales , Ratones , Astrocitos , Lesiones Encefálicas , Hipocampo , Ácido Kaínico , Neuroprotección , Fosforilación , Proteínas Proto-Oncogénicas c-akt , Regulación hacia ArribaRESUMEN
We present a new next-generation sequencing-based method to identify somatic mutations of lung cancer. It is a comprehensive mutation profiling protocol to detect somatic mutations in 30 genes found frequently in lung adenocarcinoma. The total length of the target regions is 107 kb, and a capture assay was designed to cover 99% of it. This method exhibited about 97% mean coverage at 30x sequencing depth and 42% average specificity when sequencing of more than 3.25 Gb was carried out for the normal sample. We discovered 513 variations from targeted exome sequencing of lung cancer cells, which is 3.9-fold higher than in the normal sample. The variations in cancer cells included previously reported somatic mutations in the COSMIC database, such as variations in TP53, KRAS, and STK11 of sample H-23 and in EGFR of sample H-1650, especially with more than 1,000x coverage. Among the somatic mutations, up to 91% of single nucleotide polymorphisms from the two cancer samples were validated by DNA microarray-based genotyping. Our results demonstrated the feasibility of high-throughput mutation profiling with lung adenocarcinoma samples, and the profiling method can be used as a robust and effective protocol for somatic variant screening.
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Adenocarcinoma , ADN , Exoma , Secuenciación de Nucleótidos de Alto Rendimiento , Pulmón , Neoplasias Pulmonares , Tamizaje Masivo , Polimorfismo de Nucleótido Simple , Sensibilidad y EspecificidadRESUMEN
Proteins in DNAJ/K families are ubiquitous, from prokaryotes to eukaryotes, and function as molecular chaperones. For systematic phylogenomics of the DNAJ/K families, we developed the Eukaryotic DNAJ/K Database (EDD). A total of 12,908 DNAJs and 4,886 DNAKs were identified from 339 eukaryotic genomes in the EDD. Kingdom-wide comparison of DNAJ/K families provides new insights on the evolutionary relationship within these families. Empowered by 'class', 'cluster', and 'taxonomy' browsers and the 'favorite' function, the EDD provides a versatile platform for comparative genomic analyses of DNAJ/K families.
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Humanos , Eucariontes , Genoma , Proteínas del Choque Térmico HSP40 , Proteínas HSP70 de Choque Térmico , Chaperonas Moleculares , ProteínasRESUMEN
Increased vascular permeability associated with retinal vascular leakage is known to occur in patients with diabetes, and contributes to endothelial barrier dysfunction. The purpose of this study was to examine the effect of pigment epithelium-derived factor (PEDF) on signaling cascade in porcine retinal endothelial cells (PREC) related to permeability and angiogenesis induced by vascular endothelial growth factor (VEGF)-and interleukin-1beta (IL-1beta). PREC were exposed to VEGF, IL-1beta and PEDF at different concentrations, and in vitro permeability was assessed by solute flux assay using 70-kDa RITC-dextran. Angiogenic assays such as proliferation, migration and tube formation were determined by MTT, wound-scratch method and on-gel assay system respectively. To explore the signaling pathways behind VEGF-and IL-1beta-induced PREC permeability, an inhibitor assay was carried out using PP2, a Src kinase inhibitor. Further, Src activity was assessed by transient transfection assay using constitutively active (CA) and dominant negative (DN) Src mutants. We report that VEGF-and IL-1beta-stimulates permeability, in a dose and time-dependent manner and PEDF inhibits the VEGF-and IL-1beta-induced PREC permeability. In addition, PEDF inhibits the VEGF-and IL-1beta-induced endothelial cell proliferation, migration and tube formation. In addition, overexpression of DN Src blocked both VEGF-and IL-1beta-stimulation of permeability, proliferation and migration, while overexpression of CA Src overpowers the inhibitory action of PEDF on permeability, proliferation and migration. These results demonstrate that PEDF may inhibit the VEGF-and IL-1beta-induced permeability and angiogenesis via Src-dependent pathway.
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Permeabilidad Capilar/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Proteínas del Ojo/farmacología , Interleucina-1beta/farmacología , Factores de Crecimiento Nervioso/farmacología , Retina/efectos de los fármacos , Serpinas/farmacología , Factor A de Crecimiento Endotelial Vascular/farmacología , Animales , Permeabilidad Capilar/fisiología , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Endoteliales/metabolismo , Proteínas del Ojo/metabolismo , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Neovascularización Fisiológica/fisiología , Factores de Crecimiento Nervioso/metabolismo , Retina/citología , Retina/metabolismo , Serpinas/metabolismo , Porcinos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Activation of c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is an important cellular response that modulates the outcome of the cells which are exposed to the tumor necrosis factor (TNF) or the genotoxic stress including DNA damaging agents. Although it is known that JNK is activated in response to genotoxic stress, neither the pathways to transduce signals to activate JNK nor the primary sensors of the cells that trigger the stress response have been identified. Here, we report that the receptor interacting protein (RIP), a key adaptor protein of TNF signaling, was required to activate JNK in the cells treated with certain DNA damaging agents such as adriamycin (Adr) and 1-beta-D-arabinofuranosylcytosine (Ara-C) that cause slow and sustained activation, but it was not required when treated with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and short wavelength UV, which causes quick and transient activation. Our findings revealed that this sustained JNK activation was not mediated by the TNF (tumor necrosis factor) receptor signaling, but it required a functional ATM (ataxia telangiectasia) activity. In addition, JNK inhibitor SP-600125 significantly blocked the Adr-induced cell death, but it did not affect the cell death induced by MNNG. These findings suggest that the sustained activation of JNK mediated by RIP plays an important role in the DNA damage-induced cell death, and that the duration of JNK activation relays a different stress response to determine the cell fate.
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Humanos , Muerte Celular , ADN , Daño del ADN , Doxorrubicina , Proteínas Quinasas JNK Activadas por Mitógenos , Metilnitronitrosoguanidina , Necrosis , Proteínas Quinasas , Factor de Necrosis Tumoral alfaRESUMEN
A rapidly growing number of successful genome sequencing projects in plant pathogenic fungi greatly increase the demands for tools and methodologies to study fungal pathogenicity at genomic scale. Magnaporthe oryzae is an economically important plant pathogenic fungus whose genome is fully sequenced. Recently we have reported the development and application of functional genomics platform technologies in M. oryzae. This model approach would have many practical ramifications in design and implementation of upcoming functional genomics studies of filamentous fungi aimed at understanding fungal pathogenicity.
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Agrobacterium tumefaciens , Genética , Bases de Datos Genéticas , Genoma Fúngico , Genómica , Magnaporthe , Genética , Virulencia , Mutagénesis Insercional , Oryza , Microbiología , Fenotipo , Enfermedades de las Plantas , Microbiología , Transformación Genética , Virulencia , GenéticaRESUMEN
Previous studies have demonstrated that rottlerin, a specific PKCdelta inhibitor, potentiates death receptor- mediated apoptosis through a cytochrome c-dependent or -independent pathway. However, its ability to regulate necrotic cell death, as well as the underlying mechanism, remains unknown. We found that in murine fibrosarcoma L929 cells, treatment with rottlerin protected the cells against TNF-induced necrosis, whereas it sensitized the cells to apoptosis induced by co-treatment with Hsp90 inhibitor geldanamycin and TNF, in a manner independent of its ability to inhibit PKC-delta. TNF treatment induced rapid accumulation of mitochondrial superoxide (O2") through the Nox1 NADPH oxidase when cells undergo necrosis. Moreover, pretreatment with rottlerin failed to induce the GTP-bound form of small GTPase Rac1 by TNF treatment, and subsequently suppressed mitochondrial O2(-) production and poly(ADP-ribose) polymerase activation, thus inhibiting necrotic cell death. Therefore, our study suggests that Nox1 NADPH oxidase is a new molecular target for anti-necrotic activity of rottlerin upon death-receptor ligation.
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Animales , Ratones , Acetofenonas/farmacología , Benzopiranos/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Superóxidos/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
GATA transcription factors are widespread eukaryotic regulators whose DNA-binding domain is a class IV zinc finger motif in the form CX(2)CX(17-20)CX(2)C followed by a basic region. In fungi, they act as transcriptional activators or repressors in several different processes, ranging from nitrogen source utilization to mating-type switching. Using an in-house bioinformatics portal system, we surveyed 50 fungal and 9 out-group genomes and identified 396 putative fungal GATA transcription factors. The proportion of GATA transcription factors within a genome varied among taxonomic lineages. Subsequent analyses of phylogenetic relationships among the fungal GATA transcription factors, as well as a study of their domain architecture and gene structure, demonstrated high degrees of conservation in type IVa and type IVb zinc finger motifs and the existence of distinctive clusters at least at the level of subphylum. The SFH1 subgroup with a 20-residue loop was newly identified, in addition to six well-defined subgroups in the subphylum Pezizomycotina. Furthermore, a novel GATA motif with a 21-residue loop (CX(2)CX(21)CX(2)C, designated 'zinc finger type IVc') was discovered within the phylum Basidiomycota. Our results suggest that fungal GATA factors might have undergone multiple distinct modes of evolution resulting in diversified cellular modulation in fungi.
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Basidiomycota , Biología Computacional , Dedos , Hongos , Factores de Transcripción GATA , Genoma , Nitrógeno , Sistema Porta , Dedos de ZincRESUMEN
Enterococcus hirae is a member of the Enterococcus genus and is known to cause infections in animals, but it is uncommonly encountered in clinical isolates from humans. We isolated E. hirae from blood of a patient with acute pyelonephritis and sepsis. This is the first case report of bacteremia caused by E. hirae in Korea.
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Animales , Humanos , Bacteriemia , Enterococcus , Corea (Geográfico) , Pielonefritis , SepsisRESUMEN
Enterococcus hirae is a member of the Enterococcus genus and is known to cause infections in animals, but it is uncommonly encountered in clinical isolates from humans. We isolated E. hirae from blood of a patient with acute pyelonephritis and sepsis. This is the first case report of bacteremia caused by E. hirae in Korea.
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Animales , Humanos , Bacteriemia , Enterococcus , Corea (Geográfico) , Pielonefritis , SepsisRESUMEN
BACKGROUND: Erythromycin is currently recommended as an alternative antibiotic for treatment of streptococcal infections in patients allergic to penicillins. Less than 5% of the group A streptococci are known as resistant to erythromycin but the resistance pattern differs among time and region. The purpose of this study was to determine the antimicrobial susceptibility of beta-emolytic streptococcal strains isolated during 1999 in Wonju. METHODS: A total of 107 beta-emolytic streptococci were isolates from the Wonju Christian Hospital during 1999. The susceptibility to penicillin, erythromycin, tetracycline, vancomycin, ceftriaxone, chloramphenicol, and clindamycin was tested with agar dilution method. RESULTS: No beta-emolytic streptococci strain was resistant to penicillin, ceftriaxone and vancomycin. Among beta-emolytic streptococci strains, 20-1%, 18-0% and 14-7% were resistant to tetracycline, erythromycin and clindamycin, respectively. CONCLUSIONS: It appears prudent that active surveillance of the beta-emolytic streptococci for antibiotic resistance be implemented since there are no currently effective vaccines or other methods for controlling the spread of infections due to these virulent organisms.
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Humanos , Agar , Ceftriaxona , Cloranfenicol , Clindamicina , Farmacorresistencia Microbiana , Eritromicina , Penicilinas , Infecciones Estreptocócicas , Tetraciclina , Vacunas , VancomicinaRESUMEN
BACKGROUND: Erythromycin is currently recommended as an alternative antibiotic for treatment of streptococcal infections in patients allergic to penicillins. Less than 5% of the group A streptococci are known as resistant to erythromycin but the resistance pattern differs among time and region. The purpose of this study was to determine the antimicrobial susceptibility of beta-emolytic streptococcal strains isolated during 1999 in Wonju. METHODS: A total of 107 beta-emolytic streptococci were isolates from the Wonju Christian Hospital during 1999. The susceptibility to penicillin, erythromycin, tetracycline, vancomycin, ceftriaxone, chloramphenicol, and clindamycin was tested with agar dilution method. RESULTS: No beta-emolytic streptococci strain was resistant to penicillin, ceftriaxone and vancomycin. Among beta-emolytic streptococci strains, 20-1%, 18-0% and 14-7% were resistant to tetracycline, erythromycin and clindamycin, respectively. CONCLUSIONS: It appears prudent that active surveillance of the beta-emolytic streptococci for antibiotic resistance be implemented since there are no currently effective vaccines or other methods for controlling the spread of infections due to these virulent organisms.