Induction of granule and Purkinje cells from primary cultured mouse cerebellar progenitors

International audienceThe architecturally stereotypical structure of cerebellum is ideal for investigating the generation of neuronal diversity, but in vitro models for assessing early cerebellar progenitor differentiation were lacking. Here, we report a detailed protocol for long-term in vitro generation of Pax6+ granule cells and Calbindin+ Purkinje cells from common Sox2+ embryonic cerebellar progenitors. We describe the procedure for dissecting mouse cerebellar anlage, cell seeding, and tamoxifen-induced labeling of progenitor cells, followed by time-lapse video recording of clonal expansion and neuronal differentiation

Evaluating Social Performance of Construction Projects: An Empirical Study

The concept of sustainable development is gaining increasing popularity in construction industry. Previous studies have prioritized on the sustainable performance of construction projects from perspectives of economy and environment, social performance of construction projects has not drawn much attention. Social performance of construction projects refers to the extent which the projects meet the needs of current and future generations. Therefore, social performance of construction projects is critical for project success as well as social sustainability. However, a systematic framework for evaluating social performance of construction projects is absent. At the same time, existing methods are time-consuming and subject to certain degree of subjectivity. To overcome these limitations, the fuzzy analytical hierarchy process (FAHP) method is introduced in this paper to evaluate social performance of construction projects. A real-world hospital redevelopment project was employed as an empirical study to develop the systematic framework for social performance evaluation using FAHP method. By analyzing previous studies and the hospital redevelopment project, a systematic framework with 18 indicators of five dimensions (i.e., socio-economy development, socio-environment development, social flexibility, public service development, and environment and resource conservation) was developed. Social performance of two proposed schemes for hospital redevelopment project were evaluated using the FAHP approach. Results show Scheme 2 has a relative higher social performance sore than that of Scheme 1 and the hospital redevelopment project would improve socio-economy development, socio-environment development, social flexibility, and public service development, while it brings challenges to environment and resource conservation. More seriously, results indicate the hospital project may threaten healthcare and disease prevention of the local communities. Therefore, more measures should be taken to improve social performance of the hospital redevelopment project. The empirical study shows the proposed framework using FAHP method is viable for conducting social performance evaluation of construction projects, which could be helpful to improve social performance, reduce negative social impacts, and contribute to the social sustainability of construction projects

Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage

Abstract SIRT6 is a NAD+-dependent histone deacetylase and has been implicated in the regulation of genomic stability, DNA repair, metabolic homeostasis and several diseases. The effect of SIRT6 in cerebral ischemia and oxygen/glucose deprivation (OGD) has been reported, however the role of SIRT6 in oxidative stress damage remains unclear. Here we used SH-SY5Y neuronal cells and found that overexpression of SIRT6 led to decreased cell viability and increased necrotic cell death and reactive oxygen species (ROS) production under oxidative stress. Mechanistic study revealed that SIRT6 induced autophagy via attenuation of AKT signaling and treatment with autophagy inhibitor 3-MA or knockdown of autophagy-related protein Atg5 rescued H2O2-induced neuronal injury. Conversely, SIRT6 inhibition suppressed autophagy and reduced oxidative stress-induced neuronal damage. These results suggest that SIRT6 might be a potential therapeutic target for neuroprotection

Perinatal supplementation with omega-3 polyunsaturated fatty acids improves sevoflurane-induced neurodegeneration and memory impairment in neonatal rats.

OBJECTIVES: To investigate if perinatal Omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation can improve sevoflurane-induced neurotoxicity and cognitive impairment in neonatal rats. METHODS: Female Sprague-Dawley rats (n = 3 each group) were treated with or without an n-3 PUFAs (fish oil) enriched diet from the second day of pregnancy to 14 days after parturition. The offspring rats (P7) were treated with six hours sevoflurane administration (one group without sevoflurane/prenatal n-3 PUFAs supplement as control). The 5-bromodeoxyuridine (Brdu) was injected intraperitoneally during and after sevoflurane anesthesia to assess dentate gyrus (DG) progenitor proliferation. Brain tissues were harvested and subjected to Western blot and immunohistochemistry respectively. Morris water maze spatial reference memory, fear conditioning, and Morris water maze memory consolidation were tested at P35, P63 and P70 (n = 9), respectively. RESULTS: Six hours 3% sevoflurane administration increased the cleaved caspase-3 in the thalamus, parietal cortex but not hippocampus of neonatal rat brain. Sevoflurane anesthesia also decreased the neuronal precursor proliferation of DG in rat hippocampus. However, perinatal n-3 PUFAs supplement could decrease the cleaved caspase-3 in the cerebral cortex of neonatal rats, and mitigate the decrease in neuronal proliferation in their hippocampus. In neurobehavioral studies, compared with control and n-3 PUFAs supplement groups, we did not find significant spatial cognitive deficit and early long-term memory impairment in sevoflurane anesthetized neonatal rats at their adulthood. However, sevoflurane could impair the immediate fear response and working memory and short-term memory. And n-3 PUFAs could improve neurocognitive function in later life after neonatal sevoflurane exposure. CONCLUSION: Our study demonstrated that neonatal exposure to prolonged sevoflurane could impair the immediate fear response, working memory and short-term memory of rats at their adulthood, which may through inducing neuronal apoptosis and decreasing neurogenesis. However, these sevoflurane-induced unfavorable neuronal effects can be mitigated by perinatal n-3 PUFAs supplementation

Determination of Curve Speed Zones for Mountainous Freeways

Different vehicular speed limits may have an impact on the balance between safety and efficiency of travel on mountainous road corners associated with complex road conditions. Placing suitable speed limit warning signs does not merely effectively improve traffic safety but can also improve traffic efficiency. In this study, a global positioning system (GPS) terminal and Metrocount were used to collect vehicle speed data from more than 40 provincial-level curves in 8 provinces over the course of 1 year. Each road data collection time-period lasted approximately 8 hours. A descriptive statistics method was adopted by means of data screening and pretreatment. Additionally, both a velocity difference estimation model was established and a linear model of velocity differential estimation was constructed. Quantitative analysis was carried out on the safe speed, the driver’s expected speed, and the location of the speed limit warning signs. This demonstrated a positive correlation with the initial speed. When the difference in speed was greater than 15 km/h, a safety warning sign was required to limit the design speed to 80 km/h. A safety warning sign was also required when the corner radius was less than 300 m. The location of safety warning signs could be calculated based on the operating speed and taking driving safety and the visual range of drivers into consideration. The results can provide a theoretical reference for setting up appropriate safe speed limiting signs on road corners in mountainous areas

Adjudin-preconditioned neural stem cells enhance neuroprotection after ischemia reperfusion in mice

Abstract Background Transplantation of neural stem cells (NSCs) has been proposed as a promising therapeutic strategy for the treatment of ischemia/reperfusion (I/R)-induced brain injury. However, existing evidence has also challenged this therapy on its limitations, such as the difficulty for stem cells to survive after transplantation due to the unfavorable microenvironment in the ischemic brain. Herein, we have investigated whether preconditioning of NSCs with adjudin, a small molecule compound, could enhance their survivability and further improve the therapeutic effect for NSC-based stroke therapy. Method We aimed to examine the effect of adjudin pretreatment on NSCs by measuring a panel of parameters after their transplantation into the infarct area of ipsilateral striatum 24 hours after I/R in mice. Results We found that pretreatment of NSCs with adjudin could enhance the viability of NSCs after their transplantation into the stroke-induced infarct area. Compared with the untreated NSC group, the adjudin-preconditioned group showed decreased infarct volume and neurobehavioral deficiency through ameliorating blood–brain barrier disruption and promoting the expression and secretion of brain-derived neurotrophic factor. We also employed H2O2-induced cell death model in vitro and found that adjudin preconditioning could promote NSC survival through inhibition of oxidative stress and activation of Akt signaling pathway. Conclusion This study showed that adjudin could be used to precondition NSCs to enhance their survivability and improve recovery in the stroke model, unveiling the value of adjudin for stem cell-based stroke therapy

An angular normalization method for temperature vegetation dryness index (TVDI) in monitoring agricultural drought

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Male contraceptive Adjudin is a potential anti-cancer drug

Adjudin, also known as AF-2364 and an analog of lonidamine (LND), is a male contraceptive acting through the induction of premature sperm depletion from the seminiferous epithelium when orally administered to adult rats, rabbits or dogs. It is also known that LND can target mitochondria and block energy metabolism in tumor cells. However, whether Adjudin exhibits any anti-cancer activity remains to be elucidated. Herein we described the anti-proliferative activity of Adjudin on cancer cells in vitro and on lung and prostate tumors inoculated in nude mice. We found that Adjudin induced apoptosis in cancer cells through a Caspase-3-dependent pathway. Further experiments revealed that Adjudin could trigger mitochondrial dysfunction in cancer cells, apparently affecting the mitochondrial mass, inducing the loss of mitochondrial membrane potential and reducing cellular ATP levels. Intraperitoneal administration of Adjudin to tumor-bearing athymic nude mice also significantly suppressed the lung and prostate tumor growth. When used in combination with cisplatin, Adjudin enhances the sensitivity to cisplatin-induced cancer cell cytotoxicity. Taken together, these findings have demonstrated that Adjudin may be a potential drug for cancer therapy