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1.
Front Nutr ; 10: 1249358, 2023.
Article in English | MEDLINE | ID: mdl-38024360

ABSTRACT

Introduction: Green banana flour can be used as a prebiotic due to its ability to promote gut health and provide several health benefits. In this study, we investigated whether feeding mice green banana flour at different doses would alter intestinal microbiota composition. Methods: We fed C57BL/6N mice either a Low-dose (500 mg/kg/day) or High-dose (2000 mg/kg/day) of green banana flour daily for 3 weeks, and fecal samples were collected on days 0, 14, and 21 for microbiota analysis. Results: Our results showed that the composition of intestinal microbiota was significantly altered by day 21, regardless of the dose. Notably, the consumption of green banana flour increased the presence of beneficial bacteria, including Coriobacteriaceae_UCG-002, Turicibacter, Parasutterella, Gastranaerophilales_ge, and RF39_ge. These changes in the intestinal microorganisms were accompanied by increased biological processes such as amino acid biosynthesis and secondary metabolite biosynthesis. Conversely, the consumption of green banana flour resulted in a decrease in biological processes related to carbohydrate degradation, glycerol degradation, and similar functions. Discussion: These results emphasize the potential of green banana flour as a prebiotic that can benefit the gut microbiome.

2.
J Integr Med ; 19(6): 537-544, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34580047

ABSTRACT

OBJECTIVE: Mitophagy is known to contribute towards progression of Parkinson's disease. Korean red ginseng (KRG) is a widely used medicinal herb in East Asia, and recent studies have reported that KRG prevents 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death. This study was undertaken to investigate whether KRG suppresses MPP+-induced apoptosis and mitophagy. METHODS: SH-SY5Y cells were incubated with KRG for 24 h, and subsequently exposed to MPP+. The MPP+-induced cell death was confirmed with the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Changes in the structure and function of mitochondria were confirmed using mitotracker, MitoSOX red mitochondrial superoxide indicator, parkin, and phosphatase and tensin homolog deleted on chromosome ten-induced putative kinase 1 (PINK1) immunofluorescent staining. Western blotting was performed to evaluate the expression of apoptosis-related factors in whole cells, including Bax, Bcl-2 and cleaved caspase-3, and mitophagy-related factors in the mitochondrial fraction, including cytochrome c, parkin, PINK1, translocase of the outer membrane 20 (TOM20), p62 and Beclin 1. RESULTS: MPP+ induced cell death by cytochrome c release and caspase-3 activation; however, this effect was suppressed by KRG's regulation of the expressions of Bcl-2 and Bax. Moreover, MPP+ exposure increased the mitochondrial expressions of parkin, PINK1, Beclin 1 and p62, and decreased TOM20, cytochrome c and Bcl-2 expressions. These MPP+-induced changes in the mitochondrial fraction were attenuated by treatment with KRG. CONCLUSION: KRG effectively prevents MPP+-induced SH-SY5Y cell death by regulating cytochrome c release from mitochondria and PINK1/parkin-mediated mitophagy, through regulation of the Bcl-2 family.


Subject(s)
1-Methyl-4-phenylpyridinium , Mitophagy , Panax , 1-Methyl-4-phenylpyridinium/toxicity , Apoptosis , Cell Line, Tumor , Humans , Mitochondria , Panax/chemistry , Reactive Oxygen Species
3.
J Physiol Sci ; 68(4): 455-462, 2018 Jul.
Article in English | MEDLINE | ID: mdl-28601951

ABSTRACT

Recent studies have suggested that increased oxidative stress is a potential etiology in Parkinson's disease (PD). In this study, we investigated whether acupuncture regulates antioxidants in the striatum (ST) of a PD mouse model. Male C57BL/6 mice were administered 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally once a day for 5 days and given acupuncture stimulation at SI3 or GB34 (Yanglingquan) was for 12 consecutive days. Dopaminergic neuronal survival in the nigrostriatal pathway and DJ-1 expression in the ST was evaluated by immunostaining, and the activities of superoxide dismutase (SOD) and catalase (CAT) in the ST was by enzyme-linked immunosorbent assay. MPTP administration induced dopaminergic neuronal death in the nigrostriatal pathway, which was suppressed by acupuncture stimulation at GB34. MPTP administration also suppressed DJ-1 expression and SOD and CAT activities in the ST, which were restored by acupuncture stimulation at GB34. These results indicate that the neuroprotective effect of acupuncture stimulation is due to regulation of the antioxidants.


Subject(s)
Acupuncture Therapy , Corpus Striatum/metabolism , MPTP Poisoning/metabolism , Oxidative Stress/physiology , Animals , Antioxidants/metabolism , Catalase/metabolism , Cell Survival/drug effects , Disease Models, Animal , Mice , Neurons/metabolism , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Superoxide Dismutase/metabolism
4.
Anim Cells Syst (Seoul) ; 21(1): 10-16, 2017.
Article in English | MEDLINE | ID: mdl-30460046

ABSTRACT

Sec7 protein is a guanine nucleotide exchange factor in the ADP-ribosylation factor (ARF) family of small GTP-binding proteins. Aplysia Sec7 proteins (ApSec7s) play many roles in neurite outgrowth and synaptic facilitation in Aplysia neurons. However, the binding property of Aplysia ARF1 by ApSec7 isoforms has not been examined. In this study, we found that the cloned Aplysia ARF1 (ApARF1) protein only localized to the Golgi complex when it was expressed alone in HEK293T cells; however, if ApARF1 was co-expressed with plasma membrane-targeted ApSec7, it localized to both the plasma membrane and the Golgi complex via association with the Sec7 domain of ApSec7. Moreover, in HEK293T cells expressing both ApARF1 and another Sec7 isoform, ApSec7(VPKIS), the pleckstrin homology domain of ApSec7(VPKIS) associated with ApARF1, resulting in its localization to the Golgi complex. Overall, we propose a model in which ApSec7(VPKIS) activates ApARF1 in the Golgi complex, while ApSec7 recruits ApARF1 to the plasma membrane where it activates ApARF1/6 downstream signaling.

5.
J Transl Med ; 14: 87, 2016 Apr 12.
Article in English | MEDLINE | ID: mdl-27071379

ABSTRACT

BACKGROUND: We assessed the expression of methylation-related proteins 5-meC, DNMT1, and ISL-1 in breast cancer and evaluated their relationship to clinicopathological factors. METHODS: Immunohistochemical staining for ER, PR, HER-2, Ki-67, 5-meC, DNMT1, and ISL-1 were performed on 348 breast cancer samples in tissue microarray. Samples were subgrouped into luminal A, luminal B, HER-2, or triple-negative breast cancer (TNBC) according to immunohistochemical staining for ER, PR, HER-2, and Ki-67. The tumor stroma was histologically subtyped into desmoplastic, sclerotic, normal-like, or inflammatory type. RESULTS: Tumor expression of DNMT1 differed by molecular subtype: it was higher in TNBC and lower in luminal A (p < 0.001) samples. DNMT1 expression was also related to higher histologic grade, ER negativity, PR negativity, and higher Ki-67 LI (p < 0.001). In western blot, protein expressions of DNMT1 and ISL-1 were higher in TNBC and relatively lower in the remaining subtypes. High tumor expression of DNMT1 was associated with shorter OS in univariate analysis (p = 0.041). DNMT1 and 5-meC were differentially expressed by stromal phenotype: 5-meC was higher in normal-like type and lower in sclerotic type (p = 0.049); DNMT1 was higher in inflammatory and lower in sclerotic type (p < 0.001). CONCLUSIONS: Tumor expression of DNMT1 in breast cancer differed by molecular subtype and stromal histological type. DNMT1 was highly expressed in TNBC and in breast cancer with inflammatory stromal type.


Subject(s)
DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Methylation/genetics , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Blotting, Western , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases/metabolism , Female , Humans , Middle Aged , Multivariate Analysis , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Phenotype , Prognosis , Stromal Cells/pathology , Survival Analysis
6.
Mol Brain ; 8: 85, 2015 Dec 10.
Article in English | MEDLINE | ID: mdl-26651479

ABSTRACT

BACKGROUND: Transmembrane protein 106B (TMEM106B) has been identified as a risk factor for frontotemporal lobar degeneration, which is the second most common form of progressive dementia in people under 65 years of age. Mutations in charged multivesicular body protein 2B (CHMP2B), which is involved in endosomal protein trafficking, have been found in chromosome 3-linked frontotemporal dementia. Despite the number of studies on both CHMP2B and TMEM106B in the endolysosomal pathway, little is known about the relationship between CHMP2B and TMEM106B in the endosomal/autophagy pathway. RESULTS: This study found that endogenous TMEM106B was partially sequestered in CHMP2B-positive structures, suggesting its possible involvement in endosomal sorting complexes required for transport (ESCRT)-associated pathways. The role of single nucleotide polymorphisms of TMEM106B (T185, S185, or S134N) in the ESCRT-associated pathways were characterized. The T185 and S185 variants were more localized to Rab5-/Rab7-positive endosomes compared with S134N, while all of the variants were more localized to Rab7-positive endosomes compared to Rab5-positive endosomes. T185 was more associated with CHMP2B compared to S185. Autophagic flux was slightly reduced in the T185-expressing cells compared to the control or S185-expressing cells. Moreover, T185 slightly enhanced the accumulation of EGFR, impairments in autophagic flux, and neurotoxicity that were caused by CHMP2B(Intron5) compared to S185-expressing cells. CONCLUSIONS: These findings suggest that the T185 variant functions as a risk factor in neurodegeneration with endolysosomal defects. This study provides a better understanding of pathogenic functions of TMEM106B, which is a risk factor for the progression of neurodegenerative diseases that are associated with endosomal defects in the aged brain.


Subject(s)
Endosomal Sorting Complexes Required for Transport/metabolism , Endosomes/physiology , Frontotemporal Dementia/metabolism , Membrane Proteins/physiology , Nerve Tissue Proteins/physiology , Neurons/metabolism , Polymorphism, Single Nucleotide , Protein Transport/physiology , Animals , Autophagy , Cells, Cultured , Cerebral Cortex/cytology , Cerebral Cortex/embryology , Endosomal Sorting Complexes Required for Transport/genetics , Endosomal Sorting Complexes Required for Transport/physiology , Endosomes/chemistry , Exons/genetics , Frontotemporal Dementia/genetics , Frontotemporal Dementia/pathology , HEK293 Cells , Humans , Immunoprecipitation , Introns/genetics , Lysosomes/metabolism , Membrane Proteins/genetics , Mice , Nerve Degeneration , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurons/pathology , Protein Interaction Maps , Proteolysis , Recombinant Fusion Proteins/metabolism , rab GTP-Binding Proteins/analysis , rab5 GTP-Binding Proteins/analysis , rab7 GTP-Binding Proteins
7.
Breast Cancer Res Treat ; 153(2): 323-35, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26285644

ABSTRACT

Adipocytes are known to be involved in epithelial-mesenchymal transition (EMT) in several cancers. However, the role of adipocytes in the EMT of breast cancer cells is poorly understood. The purpose of this study was to investigate the involvement of adipocytes in the EMT in breast cancer. Breast cancer cell lines MCF-7, MDA-MB-453, MDA-MB-435S, MDA-MB-231, and MDA-MB-468 were co-cultured with adipocytes and analyzed for morphological changes, proliferation activity, EMT markers, migration, and invasion. In addition, 296 human breast cancer specimens were classified according to the presence of the fibrous or adipose stroma and analyzed by immunohistochemistry for the expression of estrogen and progesterone receptors, human epidermal growth factor receptor 2, antigen Ki-67, N-cadherin, Twist-related protein 1 (TWIST1), high-mobility group AT-hook 2, TGFß, and S100 calcium-binding protein A4 using tissue microarray. After co-culture with adipocytes, MCF-7, MDA-MB-435S, and MDA-MB-231 cells exhibited elongated spindle-like morphology and increased proliferation; MDA-MB-435S and MDA-MB-231 cells also showed increased dispersion. In all tested breast cancer cells, adipocytes induced migration and invasion. The EMT-like phenotypic changes and increased cell migration and invasion were accompanied by the upregulation of matrix metallopeptidase 9 and TWIST1. Consistently, breast cancer tumors with the adipose stroma showed higher TWIST1 expression than those with the adipose stroma; however, no difference was observed in the levels of other EMT-related proteins. Adipocytes stimulate breast cancer cells to acquire aggressive tumor phenotype by inducing EMT-associated traits, and breast cancer with the adipose stroma expresses EMT markers as breast cancer with the fibrous stroma.


Subject(s)
Adipocytes/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Epithelial-Mesenchymal Transition , 3T3-L1 Cells , Adipocytes/pathology , Animals , Biomarkers , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Coculture Techniques , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression , Humans , Immunohistochemistry/methods , Mice , Neoplasm Grading , Neoplasm Staging , Phenotype , Stromal Cells/metabolism , Stromal Cells/pathology
8.
PLoS One ; 10(3): e0119473, 2015.
Article in English | MEDLINE | ID: mdl-25751270

ABSTRACT

PURPOSE: This study aimed to determine the expression and clinical significance of proteins that are involved in lipid metabolism in human breast tumors. METHODS: Tumors from 476 breast cancer patients were used to construct tissue microarrays. Then, immunohistochemistry (IHC) for hormone-sensitive lipase (HSL), Perilipin 1 (PLIN1), fatty acid binding protein 4 (FABP4), carnitine palmitoyltransferase IA (CPT-1A), acyl-CoA oxidase 1 (ACOX-1), and fatty acid synthase (FASN) was performed on these microarrays. RESULTS: Breast tumors were classified into 4 subtypes: luminal A (n = 242; 50.8%), luminal B (n = 134; 28.2%), human epidermal growth factor receptor 2 (HER2) (n = 50; 10.5%), and triple negative breast cancer (TNBC) (n = 50; 10.5%). The expression of PLIN1 (p < 0.001), FABP4 (p = 0.029), CPT-1A (p = 0.001), ACOX-1 (p < 0.001), and FASN (p < 0.001) differed significantly among these tumor subtypes. Notably, PLIN1, CPT-1A, and FASN expression was highest in HER2 tumors and lowest in TNBC tumors. Similarly, the expression of FABP4 and ACOX-1 was highest in HER2 tumors and lowest in luminal A tumors. In addition, ACOX-1 positivity was associated with significantly shorter overall survival (p = 0.018). When tumor subtype was considered, FABP4 positivity was associated with significantly shorter disease-free survival (p = 0.005) and overall survival (p = 0.041) in TNBC. CONCLUSION: Lipid metabolism-related proteins are differentially expressed in different IHC subtypes of breast cancer and some are associated with decreased survival rates.


Subject(s)
Breast Neoplasms/metabolism , Lipid Metabolism/genetics , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Gene Expression , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Middle Aged , Multivariate Analysis , Neoplasm Grading , Proportional Hazards Models
9.
Cell Cycle ; 12(8): 1303-15, 2013 Apr 15.
Article in English | MEDLINE | ID: mdl-23535298

ABSTRACT

Src family kinases (SFKs) regulate the completion of cytokinesis through signal transduction pathways that lead to the Rab11-dependent phosphorylation of ERK and its localization to the midbody of cytokinetic cells. We find that UNC119a, a known activator of SFKs, plays essential roles in this signaling pathway. UNC119a localizes to the centrosome in interphase cells and begins to translocate from the spindle pole to the spindle midzone after the onset of mitosis; it then localizes to the intercellular bridge in telophase cells and to the midbody in cytokinetic cells. We show that the midbody localization of UNC119a is dependent on Rab11, and that knocking down UNC119a inhibits the Rab11-dependent phosphorylation and midbody localization of ERK and cytokinesis. Moreover, we demonstrate that UNC119a interacts with a Src family kinase, Fyn and is required for the activation of this kinase. These results suggest that UNC119a plays a key role in the Fyn signal transduction pathway, which regulates the completion of cytokinesis via Rab11.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Cytokinesis/physiology , Proto-Oncogene Proteins c-fyn/metabolism , Signal Transduction/physiology , rab GTP-Binding Proteins/metabolism , Animals , Blotting, Western , Cloning, Molecular , HeLa Cells , Humans , Immunohistochemistry , Immunoprecipitation , Mice , Microscopy, Confocal , Oligonucleotides/genetics
10.
Ann Hematol ; 91(5): 687-695, 2012 May.
Article in English | MEDLINE | ID: mdl-22008868

ABSTRACT

To evaluate the role of FDG-PET/CT in detecting bone marrow (BM) involvement, pre-treatment bilateral bone marrow biopsies (BMBs) and FDG-PET/CT scans of 89 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-CHOP were reviewed and analyzed. Fourteen patients (15.7%) had lymphomatous involvement based on BMB (BMB+), and 17 patients (19.1%) had the possibility of BM involvement on FDG-PET/CT (FDG-PET/CT+). Seventy-two patients (80.8%) had concordant results between BMB and FDG-PET/CT (seven patients were positive for both, and 65 patients were negative for both), but 17 patients (19.2%) had a discordant interpretation (seven patients were BMB+ and FDG-PET/CT-, and ten were BMB- and FDG-PET/CT+). Although BMB+ patients had an inferior 2-year EFS (37.0% vs. 79.8%, p < 0.001) and OS (36.3% vs. 81.0%, p < 0.001) compared to BMB- patients, no differences in EFS (62.6% vs. 72.7%, p = 0.185) and OS (59.4% vs. 78.0%, p = 0.146) were shown between FDG-PET/CT+ and FDG-PET/CT- patients. Whereas six of seven patients with diffuse hypermetabolism were BMB+, only one of ten patients with focal hypermetabolism was BMB+. The results suggest that FDG-PET/CT had a limited value to detect BM involvement in patients with DLBCL. Focal hypermetabolism of hematopoietic BM in FDG-PET/CT had no impact on survival.


Subject(s)
Bone Marrow Neoplasms/diagnostic imaging , Bone Marrow Neoplasms/secondary , Fluorodeoxyglucose F18 , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/pathology , Multimodal Imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Biopsy , Bone Marrow/pathology , Bone Marrow Neoplasms/mortality , Female , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Prognosis , Survival Analysis
11.
Nucl Med Mol Imaging ; 46(4): 269-77, 2012 Dec.
Article in English | MEDLINE | ID: mdl-24900074

ABSTRACT

PURPOSE: To assess the usefulness of (18)F-fluorodeoxyglucose PET/CT in the detection of bone marrow (BM) involvement of high-grade non-Hodgkin's lymphoma (NHL). METHODS: One hundred twenty patients with newly diagnosed diffuse large B-cell lymphoma or peripheral T-cell lymphoma between January 2007 and June 2011, who received BM trephine biopsy and (18)F-FDG PET/CT before chemotherapy, were included in this retrospective study. We reviewed their (18)F-FDG PET/CT images and bone marrow biopsy (BMB) results. After reviewing the images, we reviewed the medical records and radiological findings of interesting patients. RESULTS: There were 23 (18)F-FDG PET/CT scans in which the marrow was considered to be abnormal (either positive or equivocal), and 97 (18)F-FDG PET/CT scans were regarded as having negative FDG uptake. Of 120 patients, 100 (83.3 %) had a concordant result of BM interpretation between (18)F-FDG PET/CT and BMB, and the remaining 20 patients had discordant results. Among 23 patients with either positive or equivocal (18)F-FDG PET/CT scans, 1 of 12 patients with 'positive' (18)F-FDG PET/CT had a lymphomatous involvement on BMB. In contrast, 10 of 11 patients with 'equivocal' BM hypermetabolism were reported as having positive involvement by BMB. Patients with abnormal (18)F-FDG PET/CT had significantly higher mSUVhighest than those with normal FDG-PET/CT. CONCLUSIONS: (18)F-FDG PET/CT and BMB are complementary techniques in assessing the presence of BM involvement in patients with high-grade NHL. The increasing availability of (18)F-FDG PET/CT will raise the need for additional biopsy for FDG-avid lesions, especially in patients with negative standard BMBs. (18)F-FDG PET/CT can be useful as a decision-making tool for determining whether to perform a standard BMB or targeted biopsy to the FDG-avid lesion as an initial staging procedure. A direct bone biopsy for FDGpositive bone lesions should be included in staging guidelines in future. In (18)F-FDG PET/CT-negative cases, BMB is still a powerful procedure, but BMB alone is insufficient for full evaluation of BM.

12.
Nucl Med Mol Imaging ; 45(2): 111-6, 2011 Jun.
Article in English | MEDLINE | ID: mdl-24899989

ABSTRACT

OBJECTIVE: Until now, serum tumor markers, physical examination, and conventional imaging modalities, such as CT or MRI, have been used in assessment of recurrence of cervical cancer after treatment. However, CT and MRI provide only anatomical data, which makes analysis of post-treatment change difficult. This study aims to explore the effectiveness of PET/CT, a new scanning device that combines PET and CT, in evaluation of cervical cancer lesions in patients with suspected recurrence. METHODS: We studied 51 patients suspected of recurrence among those who underwent F-18 FDG PET/CT for cervical cancer follow-up at Gachon University Gil Hospital between June 2006 and August 2009. Patients were considered to be at risk for recurrence if they reported symptoms that were clinically suggestive of recurrence, or if physical examination showed abnormalities, serum tumor marker levels rose, or follow-up images revealed changes, such as new lesions or swelling of previous sites. Sensitivity, accuracy, specificity, and positive and negative predictive values of PET/CT were measured. RESULTS: A total of 37 patients were confirmed with recurrence or metastasis, 13 of whom were diagnosed histologically. Measured across all patients, PET/CT scored 97.3% on sensitivity, 71.4% on specificity, a positive predictive value of 90%, a negative predictive value of 90.9%, and an accuracy of 90.2%. PET/CT yielded only one false negative diagnosis and four false positives. CONCLUSION: As F-18 FDG PET/CT has high sensitivity and negative predictive value in diagnosis of recurrent cervical cancers, it is expected that it will be useful for clinical determination of recurrence and prevention of unnecessary additional treatments. The hope is that a future study on a larger scale will contribute further to determination of the efficacy of PET/CT.

13.
Nucl Med Mol Imaging ; 44(2): 157-8, 2010 Jun.
Article in English | MEDLINE | ID: mdl-25013530

ABSTRACT

The authors report brain images of 18F-FDG-PET in a case of schizophrenia. The images showed strikingly increased bilateral uptake in the locus ceruleus. The locus ceruleus is called the blue spot and known to be a center of the norepinephrinergic system.

14.
J Cogn Neurosci ; 22(4): 655-69, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19320550

ABSTRACT

Neuroimaging data emphasize that older adults often show greater extent of brain activation than younger adults for similar objective levels of difficulty. A possible interpretation of this finding is that older adults need to recruit neuronal resources at lower loads than younger adults, leaving no resources for higher loads, and thus leading to performance decrements [Compensation-Related Utilization of Neural Circuits Hypothesis; e.g., Reuter-Lorenz, P. A., & Cappell, K. A. Neurocognitive aging and the compensation hypothesis. Current Directions in Psychological Science, 17, 177-182, 2008]. The Compensation-Related Utilization of Neural Circuits Hypothesis leads to the prediction that activation differences between younger and older adults should disappear when task difficulty is made subjectively comparable. In a Sternberg memory search task, this can be achieved by assessing brain activity as a function of load relative to the individual's memory span, which declines with age. Specifically, we hypothesized a nonlinear relationship between load and both performance and brain activity and predicted that asymptotes in the brain activation function should correlate with performance asymptotes (corresponding to working memory span). The results suggest that age differences in brain activation can be largely attributed to individual variations in working memory span. Interestingly, the brain activation data show a sigmoid relationship with load. Results are discussed in terms of Cowan's [Cowan, N. The magical number 4 in short-term memory: A reconsideration of mental storage capacity. Behavioral and Brain Sciences, 24, 87-114, 2001] model of working memory and theories of impaired inhibitory processes in aging.


Subject(s)
Aging/physiology , Brain Mapping , Brain/physiology , Memory, Short-Term/physiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Analysis of Variance , Brain/blood supply , Female , Functional Laterality , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Models, Neurological , Neuropsychological Tests , Oxygen/blood , Photic Stimulation , Reaction Time/physiology , Young Adult
15.
FEMS Microbiol Lett ; 294(1): 119-25, 2009 May.
Article in English | MEDLINE | ID: mdl-19493015

ABSTRACT

Of the 316 actinomycetes strains isolated from various habitats, Streptomyces sp. strain JJ45 showed the strongest antibiotic activity against the plant pathogenic bacteria Xanthomonas campestris pv. campestris and was thus chosen for further study. The 16S rRNA gene sequence (1500 bp) and rpoB gene partial sequence (306 bp) of Streptomyces strains JJ45A and JJ45B were determined. The respective strain JJ45B sequences exhibited 96.8% identity with the Streptococcus gelaticus 16S rRNA gene sequence and 98.4% identity with the Streptococcus vinaceus ATCC 27478 rpoB partial sequence. The fermentation broth of the JJ45B strain was extracted to find an inhibitor of bacterial growth. The distilled water extract showed the highest activity against pathogenic bacteria. The active molecule was isolated by column chromatography on polyacrylamide or silica gel, thin-layer chromatography, and HPLC. It showed growth inhibition activity only toward phytopathogenic Xanthomonas sp. The structure of the compound was identified as alpha-l-sorbofuranose (3-->2)-beta-D-altrofuranose based on the interpretation of the nuclear magnetic resonance spectra.


Subject(s)
Anti-Bacterial Agents/pharmacology , Disaccharides/pharmacology , Streptomyces/chemistry , Xanthomonas campestris/drug effects , Anti-Bacterial Agents/isolation & purification , Bacterial Proteins/genetics , Chromatography, Gel , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , DNA-Directed RNA Polymerases/genetics , Disaccharides/chemistry , Disaccharides/isolation & purification , Molecular Sequence Data , Molecular Structure , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Streptomyces/classification , Streptomyces/genetics
16.
Psychophysiology ; 45(5): 825-38, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18627534

ABSTRACT

Fitness and education may protect against cognitive impairments in aging. They may also counteract age-related structural changes within the brain. Here we analyzed volumetric differences in cerebrospinal fluid and gray and white matter, along with neuropsychological data, in adults differing in age, fitness, and education. Cognitive performance was correlated with fitness and education. Voxel-based morphometry was used for a whole-brain analysis of structural magnetic resonance images. We found age-related losses in gray and white matter in medial-temporal, parietal, and frontal areas. As in previous work, fitness within the old correlated with preserved gray matter in the same areas. In contrast, higher education predicted preserved white matter in inferior frontal areas. These data suggest that fitness and education may both be predictive of preserved cognitive function in aging through separable effects on brain structure.


Subject(s)
Aging/physiology , Brain/anatomy & histology , Brain/physiology , Education , Physical Fitness/physiology , Adult , Aged , Aged, 80 and over , Cardiovascular Physiological Phenomena , Female , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests
17.
FEMS Microbiol Lett ; 266(2): 236-40, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17132150

ABSTRACT

Streptomyces coelicolor A3(2) produces an antibiotic, actinorhodin, which belongs to the aromatic polyketides and which can function as an acid/base indicator. Its production results in the death of microorganisms in the vicinity of S. coelicolor A3(2), and this phenomenon can be used in concert with biopesticides. The exogenous addition of S-adenosyl-L-methionine (SAM) to S. coelicolor A3(2) enhances its actinorhodin production and may initiate actinorhodin biosynthesis, with at least four genes being involved. Of these (because afsK initiates the others), AfsK, the protein expressed from afsK, may be interacting with SAM. Although the three-dimensional structure of AfsK has not been determined, the differences between nuclear magnetic resonance (NMR) signals obtained from the free form of SAM and those from a SAM-protein complex can help us to determine whether SAM binds to the C-terminal of AfsK or not. In the present study, NMR data analysis strongly supported the idea that SAM binds to AfsK.


Subject(s)
Bacterial Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , S-Adenosylmethionine/pharmacology , Streptomyces coelicolor/metabolism , Anthraquinones/metabolism , Bacterial Proteins/genetics , Electrophoresis, Polyacrylamide Gel , Gene Expression Regulation, Bacterial/drug effects , Magnetic Resonance Spectroscopy , Protein Binding , Protein Serine-Threonine Kinases/genetics , Streptomyces coelicolor/genetics
18.
Comput Biol Med ; 34(1): 15-33, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14741727

ABSTRACT

In this paper, we present quantitative analysis of cardiac images using an efficient physical deformation model to evaluate ventricular function. By using this model we can accurately and efficiently compute ventricular volume, myocardial mass, endo- and epi-cardial wall motions and wall thickness over a full cardiac cycle. Patients with cardiac diseases were studied in our modeling and measurement framework using gated single-photon emission computed tomographic images. The results show that quantitative analysis using the model is very useful for the assessment of the extent and severity of myocardial ischemia or infarction. And it could be helpful to improve the decision-making process in the treatment of patients with cardiac diseases.


Subject(s)
Gated Blood-Pool Imaging , Heart/diagnostic imaging , Models, Biological , Models, Theoretical , Tomography, Emission-Computed, Single-Photon , Coronary Artery Disease/diagnostic imaging , Humans , Imaging, Three-Dimensional , Myocardial Ischemia/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging
19.
J Pharmacol Exp Ther ; 304(2): 706-12, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12538825

ABSTRACT

Papaverine, 1-[(3,4-dimethoxyphenyl)methyl]-6,-7-dimethoxyisoquinoline, has been used as a vasodilator agent and a therapeutic agent for cerebral vasospasm, renal colic, and penile impotence. We examined the effects of papaverine on a rapidly activating delayed rectifier K(+) channel (hKv1.5) cloned from human heart and stably expressed in Ltk(-) cells as well as a corresponding K(+) current (the ultrarapid delayed rectifier, I(Kur)) in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, we found that papaverine inhibited hKv1.5 current in a time- and voltage-dependent manner with an IC(50) value of 43.4 microM at +60 mV. Papaverine accelerated the kinetics of the channel inactivation, suggesting the blockade of open channels. Papaverine (100 microM) also blocked I(Kur) in human atrial myocytes. These results indicate that papaverine blocks hKv1.5 channels and native hKv1.5 channels in a concentration-, voltage-, state-, and time-dependent manner. This interaction suggests that papaverine could alter cardiac excitability in vivo.


Subject(s)
Myocytes, Cardiac/drug effects , Papaverine/pharmacology , Potassium Channel Blockers/pharmacology , Potassium Channels, Voltage-Gated , Potassium Channels/physiology , Animals , Cells, Cultured , Child, Preschool , Delayed Rectifier Potassium Channels , Heart Atria/cytology , Heart Atria/drug effects , Humans , Infant , Kv1.5 Potassium Channel , Membrane Potentials/drug effects , Membrane Potentials/physiology , Mice , Myocytes, Cardiac/physiology
20.
J Pharmacol Exp Ther ; 302(1): 314-9, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12065732

ABSTRACT

KCB-328 [1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N-methylamino]ethane hydrochloride] is a newly synthesized class III antiarrhythmic drug and is known to be highly effective against various types of arrhythmias induced by coronary artery ligation, reperfusion, and programmed electrical stimulation. To understand the potential ionic mechanisms, we examined the effects of KCB-328, which encodes the rapidly activating delayed rectifier K(+) current in cardiac tissues, on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes. The amplitudes of steady-state currents and tail currents of HERG were decreased by KCB-328 dose dependently. The decrease became more pronounced at more positive potential, suggesting that the block of HERG by KCB-328 is voltage-dependent. IC(50) values at -30, -20, -10, 0, +10, +20, +30, and +40 mV were 7.6 +/- 0.5, 4.8 +/- 0.4, 3.2 +/- 0.3, 2.1 +/- 0.3, 1.7 +/- 0.2, 1.4 +/- 0.2, 1.3 +/- 0.1, and 1.2 +/- 0.1 microM, respectively. Induction of block depended on depolarization beyond the threshold for channel opening. In addition, time-dependent block developed slowly, with tau = 1.7 +/- 0.3 s (100 microM) at 0 mV, and was delayed by a stronger depolarization to +80 mV, at which HERG channel is inactivated. We can conclude that KCB-328 preferentially blocks open (or activated) HERG channels. The block of HERG current might in part explain the underlying ionic mechanism for the antiarrhythmic and proarrhythmic effect of KCB-328.


Subject(s)
Cation Transport Proteins , DNA-Binding Proteins , Phenethylamines/pharmacology , Potassium Channel Blockers , Potassium Channels, Voltage-Gated , Sulfonamides/pharmacology , Trans-Activators , Action Potentials/drug effects , Algorithms , Animals , Anti-Arrhythmia Agents/pharmacology , ERG1 Potassium Channel , Ether-A-Go-Go Potassium Channels , Heart/drug effects , Humans , Kinetics , Membrane Potentials/drug effects , Oocytes , Potassium Channels/genetics , Transcriptional Regulator ERG , Xenopus
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