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

Formation of fog due to stratus lowering: An observational and modeling case study

International audienceWe numerically investigate the processes responsible for a fog event formed by stratus cloud lowering, observed on December 1–2, 2016, during the experimental campaign in the northeast of France. The observations revealed a complex temporal evolution with stratus followed by a relatively drier period and then its reformation leading to fog formation by stratus lowering. Microphysicalobservations below a tethered balloon exhibit different vertical profiles of liquid water content and droplet concentration between the stratus and the fog formed below. A simulation at 100-m grid spacing reproduced the main observed characteristics of the cloud life cycle despite a time lag in stratus formation due to large-scale conditions. The advection of cloud water in the stratus and at its top appears crucial to feed the stratus lowering, resulting in radiative cooling, vertical transport, droplet sedimentation, evaporation, and cooling of the sub-cloud layer. The advection of cold or warm air in the lowest 250m, mainly driven by fine-scale orographic circulations, impacts the fog formation due to stratus cloud lowering. When non-local conditions are favourable, the most important micro-physical process to favour fog formation is the droplet sedimentation, leading to the cooling and moistening in the sub-cloud layer by evaporation. Droplet sedimentation appears more efficient when the droplet concentration is low, and a two-moment microphysical scheme is more appropriate than a one-moment scheme to reproduce the observed variability of the droplet concentration. Given the predominance of non-local processes on this case study, a three-dimensional high-resolution model appears crucial to perform accurate forecasts of fog by stratus lowering

De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia

Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding the synaptic protein SHANK3 in 285 controls and 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X and R536W) were identified in two families, one being found in three affected brothers, suggesting germline mosaicism. Zebrafish and rat hippocampal neuron assays revealed behavior and differentiation defects resulting from the R1117X mutant. As mutations in SHANK3 were previously reported in autism, the occurrence of SHANK3 mutations in subjects with a schizophrenia phenotype suggests a molecular genetic link between these two neurodevelopmental disorders

Biodiversity of cyanobacteria and other aquatic microorganisms across a freshwater to brackish water gradient determined by shotgun metagenomic sequencing analysis in the San Francisco Estuary, USA.

Blooms of Microcystis and other harmful cyanobacteria can degrade water quality by producing cyanotoxins or other toxic compounds. The goals of this study were (1) to facilitate understanding of community structure for various aquatic microorganisms in brackish water and freshwater regions with emphasis on cyanobacteria, and (2) to test a hypothesis that Microcystis genotypes that tolerate higher salinity were blooming in brackish water environments during the severe drought, 2014. Shotgun metagenomic analysis revealed that cyanobacteria dominated the brackish water region while bacteria dominated the freshwater region. A group of cyanobacteria (e.g., Aphanizomenon, Microcystis, Planktothrix, Pseudanabaena), bacteria (e.g., Bacillus, Porphyrobacter), and diatoms (Phaeodactylum and Thalassiosira) were abundant in the brackish water region. In contrast, Hassallia (cyanobacteria) and green algae (Nannochloropsis, Chlamydomonas, and Volvox) were abundant in the landward freshwater region. Station variation was also apparent. One landward sampling station located downstream of an urbanized area differed substantially from the other stations in terms of both water chemistry and community structure, with a higher percentage of arthropods, green algae, and eukaryotes. Screening of the Microcystis internal transcribed spacer region revealed six representative genotypes, and two of which were successfully quantified using qPCR (Genotypes I and VI). Both genotypes occurred predominantly in the freshwater region, so the data from this study did not support the hypothesis that salinity tolerant Microcystis genotypes bloomed in the brackish water region in 2014

Unusual cohabitation and competition between Planktothrix rubescens and Microcystis sp. (cyanobacteria) in a subtropical reservoir (Hammam Debagh) located in Algeria

International audienceSuccession in bloom-forming cyanobacteria belonging to distant functional groups in freshwater ecosystems is currently an undescribed phenomenon. However in the Hammam Debagh reservoir (Algeria), P. rubescens and Microcystis sp. co-occur and sometimes proliferate. With the aim of identifying the main factors and processes involved in this unusual cohabitation, water samples were collected monthly from February 2013 to June 2015 at the subsurface at four sampling stations and along the entire water column at one sampling station. In addition, the composition of the cyanobacterial communities was estimated by Illumina sequencing of a 16S rRNA gene fragment from samples collected over one year (October 2013-November 2014). This molecular approach showed that the Hammam Debagh reservoir displays high species richness (89 species) but very low diversity due to the high dominance of Microcystis in this community. Furthermore, it appears that Planktothrix rubescens and Microcystis sp. coexisted (from September to January) but proliferated alternately (Spring 2015 for P. rubescens and Spring 2014 and Autumn 2014/2015 for Microcystis). The main factors and processes explaining these changes in bloom-forming species seem to be related to the variation in the depth of the lake during the mixing period and to the water temperatures during the winter prior to the bloom season in spring