7 research outputs found

    Principal component analysis of leprosy patient and control populations from Yuxi and reported Han Chinese populations across China.

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    <p>(a) PC map of Han regional populations based on mtDNA haplogroup frequencies (>1%). The patient (YuxiCase) and control (YuxiControl) populations from Yuxi were marked by triangles, whereas the reported Han Chinese populations (Zhang et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038848#pone.0038848-Zhang1" target="_blank">[28]</a> and references therein) were marked by open circles. (b) Plot of the haplogroup contribution to the first and second PCs.</p

    Demographic information and mtDNA content in the case and control groups.

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    *<p>The mean age varied in each group of subjects (Mean ± SD, Yuxi case: 61.1±12.3; Wenshan case: 34.5±21.3; Control: 39.9±16.8).</p>†<p>Student's unpaired t test (two-sided) was used to quantify the differences.</p>#<p>Two cases from Yuxi had unclear leprosy types were excluded. All leprosy patients from Wenshan received no treatment prior to blood sample collection.</p

    Relative levels of mtDNA copy number in leprosy patients with different grades of disability.

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    <p>One-way analysis of variance (ANOVA) of the mean values was used to analyze the difference of mtDNA copy number among groups (with a <i>P</i> value <0.001) and the Dunnett’s test was used for multiple comparisons between any of the two groups.</p

    Haplogroup frequencies and Pearson’s chi-square test in leprosy patients and controls from Yuxi, Yunnan Province in Southwest China.

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    *<p><i>P</i>-value was calculated by Pearson’s chi-square test; Fisher's exact test was used when haplogroup occurred in less than five individuals.</p>#<p>Haplogroup occurred in less than four individuals in the entire case or control population and those unassigned M*, N* and R* mtDNAs were pooled together. We presented these nested haplogroups according to their phylogenetic positions, e.g. D contains D4, D5, D6 and D*.</p

    Comparison of the relative mtDNA copy number in leprosy patients (n = 308) and matched healthy controls (n = 231).

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    <p>Student’s unpaired <i>t</i> test was used to quantify the statistical difference between the leprosy patient and control groups. Leprosy patients were either grouped into multibacillary leprosy (MB) and paucibacillary leprosy (PB) according to the latest WHO case definition <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038848#pone.0038848-WHO2" target="_blank">[25]</a> or into lepromatous (LL), borderline-lepromatous (BL), mid-borderline leprosy (BB), borderline-tuberculoid (BT), and tuberculoid (TT) based on the Ridley–Jopling classification <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038848#pone.0038848-Ridley1" target="_blank">[24]</a>. One-way analysis of variance (ANOVA) of the mean values was used to analyze the difference of mtDNA copy number among groups (for comparison among MB, PB and control groups, <i>P</i> = 0.089; for comparison among LL, BL, BB, BT, TT and control groups, <i>P</i> = 0.003); the Dunnett’s test was further used for multiple comparisons between any of the two groups. The 12 untreated leprosy samples from Wenshan were marked with stars in MB, PB and case groups, and the two patients with unclear classification were excluded from the analysis when we grouped the patients into MB and PB groups.</p

    <i>Atg5</i>- and <i>Atg7</i>-dependent autophagy in dopaminergic neurons regulates cellular and behavioral responses to morphine

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    <p>The molecular basis of chronic morphine exposure remains unknown. In this study, we hypothesized that macroautophagy/autophagy of dopaminergic neurons would mediate the alterations of neuronal dendritic morphology and behavioral responses induced by morphine. Chronic morphine exposure caused <i>Atg5</i> (autophagy-related 5)- and <i>Atg7</i> (autophagy-related 7)-dependent and dopaminergic neuron-specific autophagy resulting in decreased neuron dendritic spines and the onset of addictive behaviors. In cultured primary midbrain neurons, morphine treatment significantly reduced total dendritic length and complexity, and this effect could be reversed by knockdown of <i>Atg5</i> or <i>Atg7</i>. Mice deficient for <i>Atg5</i> or <i>Atg7</i> specifically in the dopaminergic neurons were less sensitive to developing a morphine reward response, behavioral sensitization, analgesic tolerance and physical dependence compared to wild-type mice. Taken together, our findings suggested that the <i>Atg5</i>- and <i>Atg7</i>-dependent autophagy of dopaminergic neurons contributed to cellular and behavioral responses to morphine and may have implications for the future treatment of drug addiction.</p

    Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated autophagy and SNCA/α-synuclein aggregation

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    <p>Autophagy is involved in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). However, little is known about the regulation of autophagy in neurodegenerative process. In this study, we characterized aberrant activation of autophagy induced by neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and demonstrated that melatonin has a protective effect on neurotoxicity. We found an excessive activation of autophagy in monkey brain tissues and C6 cells, induced by MPTP, which is mediated by CDK5 (cyclin-dependent kinase 5). MPTP treatment significantly reduced total dendritic length and dendritic complexity of cultured primary cortical neurons and melatonin could reverse this effect. Decreased TH (tyrosine hydroxylase)-positive cells and dendrites of dopaminergic neurons in the substantia nigra pars compacta (SNc) were observed in MPTP-treated monkeys and mice. Along with decreased TH protein level, we observed an upregulation of CDK5 and enhanced autophagic activity in the striatum of mice with MPTP injection. These changes could be salvaged by melatonin treatment or knockdown of CDK5. Importantly, melatonin or knockdown of CDK5 reduced MPTP-induced SNCA/α-synuclein aggregation in mice, which is widely thought to trigger the pathogenesis of PD. Finally, melatonin or knockdown of CDK5 counteracted the PD phenotype in mice induced by MPTP. Our findings uncover a potent role of CDK5-mediated autophagy in the pathogenesis of PD, and suggest that control of autophagic pathways may provide an important clue for exploring potential target for novel therapeutics of PD.</p
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