Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia

Pharmacological, genetic and expression studies implicate N-methyl-D-aspartate (NMDA) receptor hypofunction in schizophrenia (SCZ). Similarly, several lines of evidence suggest that autism spectrum disorders (ASD) could be due to an imbalance between excitatory and inhibitory neurotransmission. As part of a project aimed at exploring rare and/or de novo mutations in neurodevelopmental disorders, we have sequenced the seven genes encoding for NMDA receptor subunits (NMDARs) in a large cohort of individuals affected with SCZ or ASD (n=429 and 428, respectively), parents of these subjects and controls (n=568). Here, we identified two de novo mutations in patients with sporadic SCZ in GRIN2A and one de novo mutation in GRIN2B in a patient with ASD. Truncating mutations in GRIN2C, GRIN3A and GRIN3B were identified in both subjects and controls, but no truncating mutations were found in the GRIN1, GRIN2A, GRIN2B and GRIN2D genes, both in patients and controls, suggesting that these subunits are critical for neurodevelopment. The present results support the hypothesis that rare de novo mutations in GRIN2A or GRIN2B can be associated with cases of sporadic SCZ or ASD, just as it has recently been described for the related neurodevelopmental disease intellectual disability. The influence of genetic variants appears different, depending on NMDAR subunits. Functional compensation could occur to counteract the loss of one allele in GRIN2C and GRIN3 family genes, whereas GRIN1, GRIN2A, GRIN2B and GRIN2D appear instrumental to normal brain development and function

Protective Effect of <i>Aquilaria crassna</i> Leaf Extract against Benzo[a]pyrene-Induced Toxicity in Neuronal Cells and <i>Caenorhabditis elegans</i>: Possible Active Constituent Includes Clionasterol

Aquilaria crassna (AC) is a beneficial plant widely used to alleviate various health ailments. Nevertheless, the neuroprotection, antiaging, and xenobiotic detoxification against high benzo[a]pyrene induction have not been investigated. This study aimed to investigate the effects of ethanolic extract of AC leaves (ACEE) in vitro using SH-SY5Y cells and in vivo using Caenorhabditis elegans (C. elegans). Neuroprotective activities and cell cycle progression were studied using SH-SY5Y cells. Additionally, C. elegans was used to determine longevity, health span, and transcriptional analysis. Furthermore, ACEE possible active compounds were analyzed by gas chromatograph–mass spectrometry (GC-MS) analysis and the possible active compounds were evaluated using a molecular docking study. First, ACEE possessed neuroprotective effects by normalizing cell cycle progression via the regulation of AhR/CYP1A1/cyclin D1 pathway. Next, ACEE played a role in xenobiotic detoxification in high B[a]P-induced C. elegans by the amelioration of lifespan reduction, and body length and size decrease through the reduction in gene expression in hexokinase (hxk) and CYP35 pathway. Finally, phytochemicals of ACEE were identified and we uncovered that clionasterol was the possible active constituent in powerfully inhibiting both CYP1A1 and hexokinase II receptor. Essentially, ACEE was recognized as a potential alternative medicine to defend against high B[a]P effects on neurotoxicity and xenobiotic detoxification

Etude de l'épaisseur d'isolation thermique économique et optimale pour les bâtiments sous climat tropical humide et chaud: cas du Cameroun

In Cameroon, these last centuries, an increase in energy demand for cooling and heating in buildings has been witnessed all over the world. Solutions must be proposed by researchers and specialists of buildings to remedy this situation. In this study, a literature review on the thermal insulation applications to external walls of buildings was presented, and a case was investigated in a tropical wet and hot climate. The economic model including the cost of insulation material and the present value of energy consumption and the cost over a lifetime of 22 years of the building, were used to find the optimum insulation thickness, energy saving, and payback period, for buildings in Cameroon. Materials that extruded polystyrene were chosen and used for two typical wall structures (Concrete block (HCB) and compressed stabilized earth block wall (CSEB)). The yearly cooling transmission loads, according to wall orientations and percentage of radiation blocked were calculated using the explicit finite-difference method under steady periodic conditions. As a result, it was found that the lowest value of optimum insulation thickness (0.09 m) and energy savings (79.80%) were obtained for the south-oriented wall, while the payback period (4.73years) was the highest on the same face compared to all wall orientations. Insulation optimum thickness was higher in the HCB wall (0.0983 m) than in CSEB wall (0.0958 m), however, the payback period was the weakest for the HCB wall compared to the other wall type

<i>Aquilaria crassna</i> Leaf Extract Ameliorates Glucose-Induced Neurotoxicity In Vitro and Improves Lifespan in <i>Caenorhabditis elegans</i>

Hyperglycemia is one of the important causes of neurodegenerative disorders and aging. Aquilaria crassna Pierre ex Lec (AC) has been widely used to relieve various health ailments. However, the neuroprotective and anti-aging effects against high glucose induction have not been investigated. This study aimed to investigate the effects of hexane extract of AC leaves (ACH) in vitro using human neuroblastoma SH-SY5Y cells and in vivo using nematode Caenorhabditis elegans. SH-SY5Y cells and C. elegans were pre-exposed with high glucose, followed by ACH treatment. To investigate neuroprotective activities, neurite outgrowth and cell cycle progression were determined in SH-SY5Y cells. In addition, C. elegans was used to determine ACH effects on antioxidant activity, longevity, and healthspan. In addition, ACH phytochemicals were analyzed and the possible active compounds were identified using a molecular docking study. ACH exerted neuroprotective effects by inducing neurite outgrowth via upregulating growth-associated protein 43 and teneurin-4 expression and normalizing cell cycle progression through the regulation of cyclin D1 and SIRT1 expression. Furthermore, ACH prolonged lifespan, improved body size, body length, and brood size, and reduced intracellular ROS accumulation in high glucose-induced C. elegans via the activation of gene expression in the DAF-16/FoxO pathway. Finally, phytochemicals of ACH were analyzed and revealed that β-sitosterol and stigmasterol were the possible active constituents in inhibiting insulin-like growth factor 1 receptor (IGFR). The results of this study establish ACH as an alternative medicine to defend against high glucose effects on neurotoxicity and aging

Prenatal exposure to bisphenol A alters the transcriptome-interactome profiles of genes associated with Alzheimer\u27s disease in the offspring hippocampus.

Our recent study revealed that prenatal exposure to bisphenol A (BPA) disrupted the transcriptome profiles of genes in the offspring hippocampus. In addition to genes linked to autism, several genes associated with Alzheimer\u27s disease (AD) were found to be differentially expressed, although the association between BPA-responsive genes and AD-related genes has not been thoroughly investigated. Here, we demonstrated that in utero BPA exposure also disrupted the transcriptome profiles of genes associated with neuroinflammation and AD in the hippocampus. The level of NF-κB protein and its AD-related target gene Bace1 were significantly increased in the offspring hippocampus in a sex-dependent manner. Quantitative RT-PCR analysis also showed an increase in the expression of Tnf gene. Moreover, the reanalysis of transcriptome profiling data from several previously published BPA studies consistently showed that BPA-responsive genes were significantly associated with top AD candidate genes. The findings from this study suggest that maternal BPA exposure may increase AD risk in offspring by dysregulating genes associated with AD neuropathology and inflammation and reveal a possible relationship between AD and autism, which are linked to the same environmental factor. Sex-specific effects of prenatal BPA exposure on the susceptibility of AD deserve further investigation

Using Multiple Space Assests with In-Situ Measurements to Track Flooding in Thailand

Increasing numbers of space assets can enable coordinated measurements of flooding phenomena to enhance tracking of extreme events. We describe the use of space and ground measurements to target further measurements as part of a flood monitoring system in Thailand. We utilize rapidly delivered MODIS data to detect major areas of flooding and the target the Earth Observing One Advanced Land Imager sensor to acquire higher spatial resolution data. Automatic surface water extent mapping products delivered to interested parties. We are also working to extend our network to include in-situ sensing networks and additional space assets

Combining Space-Based and In-Situ Measurements to Track Flooding in Thailand

We describe efforts to integrate in-situ sensing, space-borne sensing, hydrological modeling, active control of sensing, and automatic data product generation to enhance monitoring and management of flooding. In our approach, broad coverage sensors and missions such as MODIS, TRMM, and weather satellite information and in-situ weather and river gauging information are all inputs to track flooding via river basin and sub-basin hydrological models. While these inputs can provide significant information as to the major flooding, targetable space measurements can provide better spatial resolution measurements of flooding extent. In order to leverage such assets we automatically task observations in response to automated analysis indications of major flooding. These new measurements are automatically processed and assimilated with the other flooding data. We describe our ongoing efforts to deploy this system to track major flooding events in Thailand