Deregulation of ER-mitochondria contact formation and mitochondrial calcium homeostasis mediated by VDAC in fragile X syndrome

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Abnormality in Translational Regulation of Catalase Expression in Disorders of Peroxisomal Biogenesis

Abstract: Peroxisomal disorders are a newly described group of inherited neurological diseases. In disorders of peroxisomal biogenesis, e.g., Zellweger syndrome, owing to the lack of peroxisomes, catalase, a peroxisomal enzyme, is found to be present in the cytoplasm instead. We observed higher catalase activity (7.59 ± 0.41 mU/mg of protein) in cultured skin fibroblasts from Zellweger patients than in control fibroblasts (4.45 ± 0.29 mU/mg of protein). Moreover, we also found that the majority of the catalase in Zellweger cells was present in the inactive form. The specific activities following reactivation in Zellweger and control cells were 12.1 and 4.9 mU/mg of protein, respectively. To understand the molecular basis of higher levels of catalase in Zellweger than control cells, we examined the rate of synthesis and turnover of catalase and levels of catalase mRNA and protein levels in Zellweger cells as compared with control cells. The initial rates of synthesis of catalase in Zellweger (1.68 ± 0.15 mU/mg of protein) and control (1.51 ± 0.14 mU/mg of protein) cells were similar. The rates of turnover of catalase in Zellweger (t_1/2 = 47 ± 8 h) and control (t_1/2 = 49 ± 7 h) were also similar. Consistent with the enzyme activity, the levels of catalase protein were higher in Zellweger cells as compared with control cells. On the other hand, there was no difference in the level of catalase mRNA between control and Zellweger cells. Although the rate of synthesis in Zellweger and control cells were initially similar, it was down-regulated to a lower level at ～72 h of culture in control fibroblasts as compared with Zellweger cells, which continued to synthesize catalase at the same rate up to 5 days in culture. The presence of similar levels of mRNA in control and Zellweger cells and continued synthesis of catalase in Zellweger cells at a higher level as compared with control cells suggest a loss of regulation at the translational level.     

The Effect of Dolphin-Assisted Therapy on the Cognitive and Social Development of Children with Down Syndrome

Cognitive and speech development are delayed in children with Down syndrome (DS). We investigated the effect of dolphin-assisted therapy (DAT), a form of animal-assisted intervention, on the development of speech/language and social behavior in children with DS. We hypothesized that DAT would improve the social and cognitive functions with respect to verbalization and thereby promote task performance. A semi-crossover design was used to study 45 children with DS: 18 received a weekly one-hour session of DAT for 6 weeks (group A), 12 children (group B) started with swimming pool sessions (control period of 6 weeks) and thereafter received DAT, and 17 children (group C) were put on a waiting list (control period of 6 weeks) before receiving DAT. The parameters “verbalization,” “impulsiveness,” “proper understanding of rules,” “recognition of persons,” and “establishing contacts” were measured using the Matson Evaluation of Social Skills for Individuals with Severe Retardation (MESSIER) before and after DAT, as well as before and after each of the control periods. Repeated measures ANOVA revealed no significant changes for any of the variables during the control periods (swimming pool, waiting list). Following the period of DAT there was a significant improvement in “verbalization” and “recognition of persons,” while “impulsiveness” decreased. No significant changes were found for the other parameters. “Verbalization” continued to increase during the follow-up period of 6 months, while “recognition of persons” slightly decreased. The results of this study provide support for our hypothesis. Through improvements in verbalization and the recognition of persons, the execution of tasks among children with DS receiving DAT improved. Additional studies are needed to determine if these positive effects of DAT are long-term.     

扁桃体部分切除术最新进展

扁桃体切除术是耳鼻咽喉科最常见的手术之一,临床上治疗由于扁桃体肥大所致的儿童睡眠阻塞性呼吸暂停综合征,最常用的手术方式为双侧扁桃体切除术。扁桃体在儿童生长发育过程中具有重要的免疫功能,完全切除扁桃体对儿童的免疫功能具有一定的影响。且扁桃体全部切除术后常见一些并发症如出血及疼痛,这使得许多学者提出了扁桃体部分切除术。扁桃体部分切除术较扁桃体全部切除术相比,手术时间短、术后并发症少,在缓解儿童阻塞症状的同时,保留了一部分扁桃体,对于免疫功能也有一定的保留。本文将从扁桃体部分切除术治疗儿童睡眠呼吸暂停综合征的临床疗效以及术后出血、术后疼痛方面作一综述,为扁桃体部分切除术应用于临床提供合理依据。     

Effect of Cynomorium total flavone on depression model of perimenopausal rat

PurposeTo observe the effect of cynomorium total flavone on the depression model of perimenopausal rat and to analyze the action characteristics of cynomorium total flavone on depression of rat with perimenopausal syndrome.MethodDuplicate the model of rat with perimenopausal depression based on the combined method of incomplete castration and chronic stimulation, and keep drug administration for 35d. And then measure related behavior indicators and the change of biochemical index level in serum and brains; measure the estrogen/androgen receptor (ER/AR) in related tissues and the ERmRNA expression in hypothalamus.ResultIt can be seen that cynomorium total flavone can significantly improve the behavior indicators of rat with perimenopausal depression; obviously or significantly change the level of related biomedical indexes in serum and brains of perimenopausal depressed rat; obviously or significantly increase the expression of ER/AR in related tissues of perimenopausal depressed rat; obviously or significantly increase the ERmRNA expression in hypothalamus.ConclusionCynomorium total flavone can adjust hypothalamic-pituitary-gonadal axis by increasing E2, and make related biomedical indexes and hormone receptors tend to be normal, so as to relieve perimenopausal syndrome and perimenopausal syndrome with depression.     

Immunolocalization of the Na,K-ATPase in photoreceptor cells of the moth Manduca sexta-evidence for Na,K-ATPase on both the nonmicrovillar and the microvillar domains of the plasma membrane

Immunohistochemical and physiological studies on various insect photoreceptors have demonstrated that the Na,K-ATPase (sodium pump) is restricted to the nonreceptive nonmicrovillar area of the plasma membrane. Here, we examined the distribution of the Na,K-ATPase in photoreceptor cells of the superposition-type compound eye in the moth Manduca sexta. Using immunofluorescent and immunogold cytochemistry, we show that the Na,K-ATPase is localized to both the nonmicrovillar and the microvillar parts of the plasma membrane. Manduca photoreceptors thus deviate from the common concept that the sodium pump and the molecular components of the photoreceptive machinery reside on different domains of the plasma membrane.     

Biomarkers in critically ill patients with systemic inflammatory response syndrome or sepsis supplemented with high-dose selenium

ObjectiveLow levels of selenium (Se) and glutathione peroxidase (GSHPx), a key selenoenzyme, were documented in systemic inflammatory response syndrome (SIRS) and sepsis, both associated with high mortality. Se supplementation had mixed effects on outcome. We hypothesized that Se supplementation could have a different impact on biomarkers and 28-day mortality in patients with SIRS vs. sepsis.MethodsAdult patients with SIRS or sepsis were randomized to either high-dose (Se+, n = 75) or standard-dose (Se−, n = 75) Se supplementation. Plasma Se, whole blood GSHPx activity, C-reactive protein (CRP), procalcitonin (PCT), prealbumin, albumin and cholesterol levels were measured serially up to day 14.ResultsThere was no difference in mortality between Se− (24/75) vs. Se+ group (19/75; p = 0.367) or between SIRS and septic patients (8/26 vs. 35/124; p = 0.794). There was a trend to reduced mortality in SIRS patients in the Se+ vs. Se− group (p = 0.084). Plasma Se levels increased in the Se+ group only in patients with sepsis but not in patients with SIRS. Plasma Se levels correlated with GSHPx. In SIRS/Se+ group, Se correlated only with GSHPx. In SIRS/Se− group, Se correlated with cholesterol but not with other biomarkers. In sepsis patients, Se levels correlated with cholesterol, GSHPx and prealbumin. Cholesterol levels were higher in survivors in the Se− group.ConclusionsSe levels correlated with GSHPx activity and other nutritional biomarkers with significant differences between SIRS and sepsis groups. High-dose Se supplementation did not affect mortality but a strong trend to decreased mortality in SIRS patients warrants further studies in this population.     

Selection of visual information for lightness judgements by eye movements

When judging the lightness of objects, the visual system has to take into account many factors such as shading, scene geometry, occlusions or transparency. The problem then is to estimate global lightness based on a number of local samples that differ in luminance. Here, we show that eye fixations play a prominent role in this selection process. We explored a special case of transparency for which the visual system separates surface reflectance from interfering conditions to generate a layered image representation. Eye movements were recorded while the observers matched the lightness of the layered stimulus. We found that observers did focus their fixations on the target layer, and this sampling strategy affected their lightness perception. The effect of image segmentation on perceived lightness was highly correlated with the fixation strategy and was strongly affected when we manipulated it using a gaze-contingent display. Finally, we disrupted the segmentation process showing that it causally drives the selection strategy. Selection through eye fixations can so serve as a simple heuristic to estimate the target reflectance.     

CaV1.2 I-II linker structure and Timothy syndrome

Ca_V channels are multi-subunit protein complexes that enable inward cellular Ca²⁺ currents in response to membrane depolarization. We recently described structure-function studies of the intracellular α1 subunit domain I-II linker, directly downstream of domain IS6. The results show the extent of the linker’s helical structure to be subfamily dependent, as dictated by highly conserved primary sequence differences. Moreover, the difference in structure confers different biophysical properties, particularly the extent and kinetics of voltage and calcium-dependent inactivation. Timothy syndrome is a human genetic disorder due to mutations in the Ca_V1.2 gene. Here, we explored whether perturbation of the I-II linker helical structure might provide a mechanistic explanation for a Timothy syndrome mutant’s (human Ca_V1.2 G406R equivalent) biophysical effects on inactivation and activation. The results are equivocal, suggesting that a full mechanistic explanation for this Timothy syndrome mutation requires further investigation.     

Zooming in on Cadherin-23: Structural Diversity and Potential Mechanisms of Inherited Deafness

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