Excessive Dpp signaling induces cardial apoptosis through dTAK1 and dJNK during late embryogenesis of Drosophila

<p>Abstract</p> <p>Background</p> <p>To identify genes involved in the heart development of <it>Drosophila</it>, we found that embryos lacking <it>raw </it>function exhibited cardial phenotypes. <it>raw </it>was initially identified as a dorsal open group gene. The dorsal open phenotype was demonstrated to be resulted from the aberrant expression of <it>decapentaplegic </it>(<it>dpp</it>), a member of the tumor growth factor beta (TGF-β), signaling pathway. Despite the role of <it>dpp </it>in pattering cardioblasts during early embryogenesis of <it>Drosophila </it>have been demonstrated, how mutation in <it>raw </it>and/or excessive <it>dpp </it>signaling involves in the differentiating heart of <it>Drosophila </it>has not been fully elaborated at late stages.</p> <p>Results</p> <p>We show that <it>raw </it>mutation produced a mild overspecification of cardial cells at stage 14, but these overproduced cells were mostly eliminated in late mutant embryos due to apoptosis. Aberrant <it>dpp </it>signaling is likely to contribute to the cardial phenotype found in <it>raw </it>mutants, because expression of <it>dpp </it>or constitutively activated <it>thickven </it>(<it>tkv^CA</it>), the type I receptor of Dpp, induced a <it>raw</it>-like phenotype. Additionally, we show that <it>dpp </it>induced non-autonomous apoptosis through TGFβ activated kinase 1 (<it>TAK1</it>), because mis-expression of a dominant negative form of <it>Drosophila TAK1 </it>(<it>dTAK1^DN</it>) was able to suppress cell death in <it>raw </it>mutants or embryos overexpressing <it>dpp</it>. Importantly, we demonstrated that <it>dpp </it>induce its own expression through <it>dTAK1</it>, which also leads to the hyperactivation of <it>Drosophila </it>JNK (DJNK). The hyperactivated DJNK was attributed to be the cause of Dpp/DTAK1-induced apoptosis because overexpression of a dominant negative DJNK, <it>basket </it>(<it>bsk^DN</it>), suppressed cell death induced by Dpp or DTAK1. Moreover, targeted overexpression of the anti-apoptotic P35 protein, or a dominant negative proapoptotic P53 (P53^DN) protein blocked Dpp/DTAK1-induced apoptosis, and rescued heart cells under the <it>raw </it>mutation background.</p> <p>Conclusions</p> <p>We find that ectopic Dpp led to DJNK-dependent cardial apoptosis through the non-canonical TGF-β pathway during late embryogenesis of <it>Drosophila</it>. This certainly will increase our understanding of the pathogenesis of cardiomyopathy, because haemodynamic overload can up-regulate TGF-β and death of cardiomyocytes is observed in virtually every myocardial disease. Thus, our study may provide possible medical intervention for human cardiomyopathy.</p

The operation modal analysis of the structure crack fault diagnosis based on pseudo-successive data

In order to monitor the crack propagation of the structure in the working state for a long time, an operation modal analysis method based on pseudo-successive data is proposed. The vibration response signals of the cantilever beam under white noise excitation are collected and the modal parameters are extracted by the time-frequency operation modal analysis method based on the complex Morlet wavelet. In comparison with the experimental modal analysis results of hammering method, it is revealed that the error of the time-frequency operation modal analysis method is less than 10 %. By setting cracks of different lengths on the cantilever beam, the vibration response signals are extracted, and the modal parameters are extracted by the operation modal analysis method separately. By comparing those modal parameters above, it is found that the natural frequencies of the second, the fourth and the sixth orders decrease with the increase of the crack depth, and the changes of natural frequencies show the monotonicity. So, it can be used as an index for quantitative identification of crack damage. The pseudo continuous data monitoring signals of crack propagation can be constructed by means of “first discrete, then continuous”. The modal parameters changes of the whole crack propagation can be observed in one time plane by means of the operation modal analysis method. Therefore, the effective monitoring and diagnosis of the structure can be completed in case of excessive data of long-time vibration monitoring signals

Interleukin 10 promoter haplotype is associated with alcoholic liver cirrhosis in Taiwanese patients

AbstractAlcoholic liver cirrhosis is a severe form of alcohol-related liver damage. More than 95% of heavy drinkers develop a fatty liver, but only 35% of them develop cirrhosis. We postulate that genetic factors may play a role in this difference. Genetic polymorphisms of the cytokine genes may influence Kupffer cells cytokine genes expression. In this study, we evaluated the promoter polymorphisms of interleukin (IL) 1β, IL 6, IL 10, and tumor necrosis factor alpha (TNFα) and aimed to clarify the association between the polymorphisms and the disease. Forty alcoholic patients with liver cirrhosis and 64 healthy volunteers were included in our investigation. Genotyping on IL 1β –511 T>C, IL 6 –572 G>C, IL 10 –819 C>T, IL 10 –1082 G>A, and TNFα –308 G>A was done. Another 36 patients with recurrent alcoholic pancreatitis were included as an additional control group. Genotyping on IL 10 –819 C>T and IL 10 –1082 G>A was done. The polymorphisms on IL 1 and IL 6 showed no significant association. The p value for TNFα –308 G>A was 0.028 in comparison with healthy volunteers. Although the p value was less than 0.05, it did not reach significance after Bonferroni correction. The p values for IL 10 –819 C>T and IL 10 –1082 G>A were respectively 0.031 and 0.026 in healthy volunteers and 0.028 and 0.023 in the alcoholic pancreatitis group. The results also did not reach significance after Bonferroni correction. Among the participants with the GCC haplotype, healthy volunteers had p = 0.027 (p < 0.05) and an odds ratio (OR) of 0.124 [confidence interval (95%) CI, 0.015–0.997], whereas the alcoholic pancreatitis group had p = 0.023 (p < 0.05) and an OR of 0.106 (95% CI, 0.012–0.912). The odds ratio of people having one ATA haplotype was 6.233 (95% CI, 0.739–52.547) in healthy volunteers and 6.588 (95% CI, 0.727–59.679) in the alcoholic pancreatitis group; the corresponding rate was 10.521 (95% CI, 1.252–88.440) and 12.833 (95% CI 1.408–117.008) for people with two ATA haplotypes. The p values in these groups were 0.031 (p < 0.05) and 0.028 (p < 0.05), respectively. The presence of a GCC haplotype could have protective effect against alcoholic liver disease, whereas the presence of an ATA haplotype could predispose carriers to the disease. The IL 10 promoter haplotype is associated with alcoholic liver cirrhosis in Taiwanese patients

不同年龄和性别精神分裂症患者脑白质扩散张量成像的临床研究*

Objective: Diffusion tensor imaging (DTI) was used to analyze the changes of white matter fiber FA in patients with schizophrenia of different ages and genders, and to explore the reference of clinical imaging. Methods: Retrospective analysis of the clinical diagnosis of schizophrenia patients and healthy subjects in all 50 cases, were given routine examination of brain MRI parallel diffusion tensor imaging, comparison of different age and gender in different parts of the brain white matter changes of FA value. Results: (1) the FA values of white matter in different age groups were different between the patients and the normal group (P &lt; 0.05). The normal group right superior frontal gyrus, left parietal lobe and left anterior cingulate gyrus of the cerebral white matter fiber FA value increased gradually before the age of 30, at the age of 30 and reached the peak gradually decreased after 30 years old. The left frontal gyrus and corpus callosum in patients with group pressure (after) of cerebral white matter fiber FA value increased gradually before the age of 30, at the age of 30 and reached the peak gradually decreased after 30 years old. (2) the FA values of white matter in different parts of male and female patients were different (P &lt; 0.05). The white matter fiber FA in the left anterior capsule of the normal group was higher in males than in females. The FA value of bilateral occipital white matter in male patients was lower than that in female; the FA values of the central white matter in the left and right sides of the brain stem were higher in males than in females. Conclusion: the changes of FA value in the white matter of some parts of the brain in the normal group and the patient group are influenced by age and sex.  目的  运用扩散张量成像分析不同年龄和性别精神分裂症患者脑白质纤维FA值的变化，探讨临床影像学参考依据。方法  回顾性分析经临床确诊的精神分裂症患者和健康者各50例，均作颅脑MRI常规检查并行扩散张量成像，比较不同年龄和性别各部位脑白质FA值变化特点。结果  （1）患者组和正常组不同年龄各部位脑白质FA值有差异（P＜0.05）。正常组中右额上回、左顶叶及左扣带回前部脑白质纤维FA值在30岁前逐渐增高，30岁达高峰，在30岁后逐渐减少。患者组中左额上回及胼胝体压部（后）脑白质纤维FA值在30岁前逐渐增高，30岁达高峰，在30岁后逐渐减少。（2）患者组和正常组男女各部位脑白质FA值有差异（P＜0.05）。发现正常组中左侧内囊前肢脑白质纤维FA值男性较女性高。患者组中双侧枕叶脑白质纤维FA值男性较女性低；脑干左右侧中心脑白质FA值男性较女性高。结论  正常组和患者组大脑某些部位脑白质纤维FA值量的变化受年龄、性别的影响

Abnormal diastolic function underlies the different beneficial effects of cardiac resynchronization therapy on ischemic and non-ischemic cardiomyopathy

OBJECTIVES: To investigate the association between diastolic function and the different beneficial effects of cardiac resynchronization therapy in patients with heart failure due to different causes. METHODS: The 104 enrolled patients were divided into an ischemic cardiomyopathy group (n=27) and a non-ischemic cardiomyopathy group (n=77) according to the cause of heart failure. Before implantation, left ventricular diastolic function was evaluated in all patients using echocardiography. After six months of follow-up, the beneficial effects of cardiac resynchronization therapy were evaluated using a combination of clinical symptoms and echocardiography parameters. RESULTS: The ischemic cardiomyopathy group included significantly more patients with restrictive filling than the non-ischemic cardiomyopathy group. The response rate after the implantation procedure was significantly higher in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Degrees of improvement in echocardiography parameters were significantly greater in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Multivariate regression analysis showed that a restrictive filling pattern was an independent factor that influenced responses to cardiac resynchronization therapy. CONCLUSIONS: This study again confirmed that the etiology of heart failure affects the beneficial effects of cardiac resynchronization therapy and a lower degree of improvement in ventricular systolic function and remodelling was observed in ischemic cardiomyopathy patients than in non-ischemic cardiomyopathy patients. In addition, systolic heart failure patients with severe diastolic dysfunction had poor responses to cardiac resynchronization therapy. Ischemic cardiomyopathy patients exhibited more severe diastolic dysfunction than non-ischemic cardiomyopathy patients, which may be a reason for the reduced beneficial effect of cardiac resynchronization therapy