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

{P4Consist}: {T}oward Consistent {P4 SDNs}

The prevailing wisdom is that a software-defined network (SDN) operates under the premise that the logically centralized control plane has an accurate representation of the actual data plane state. Unfortunately, bugs, misconfigurations, faults or attacks can introduce inconsistencies between the network control and the data plane that can undermine the correct operation at runtime. Through our experiments, we realize that P4 SDNs are no exception, and are prone to similar problems. With the aim to verify the control-data plane inconsistency, we present the design and implementation of P4Consist, a system to detect the inconsistency between control and data plane in P4 SDNs. P4Consist generates active probe-based traffic continuously or periodically as an input to the P4 SDNs to check whether the actual behavior on the data plane corresponds to the expected control plane behavior. In P4Consist, the control plane and the data plane generate independent reports which are later, compared to verify the control-data plane consistency. The previous works in the field of monitoring and verification mostly aim to test the P4 programs through static analysis and thus, are insufficient to verify the network consistency at runtime. Experiments with our prototype implementation of P4Consist are promising and show that P4Consist can verify the control-data plane consistency in the complex datacenter 4-ary fat-tree (20 switches) and multipath grid (4, 9 and 16 switches) topologies with 60k rules per switch within a minimum time of 4 minutes. At the same time, P4Consist scales to multiple source-destination pairs to detect control-data plane inconsistency

Alexandrium pacificum Litaker sp. nov. (Group IV) : resting cyst distribution and toxin profile of vegetative cells in Bizerte Lagoon (Tunisia, Southern Mediterranean Sea)

A high spatial resolution sampling of Alexandrium pacificum cysts, along with sediment characteristics (% H2O, % organic matter (OM), granulometry), vegetative cell abundance and environmental factors were investigated at 123 study stations in Bizerte Lagoon (Tunisia). Morphological examination and ribotyping of cells obtained from a culture called ABZ1 obtained from a cyst isolated in lagoon sediment confirmed that the species was A. pacificum. The toxin profile from the ABZ1 culture harvested during exponential growth phase was simple and composed of the N-sulfocarbamoyl toxins C1 (9.82 pg toxin cell(-1)), the GTX6 (3.26 pg toxin cell(-1)) and the carbamoyl toxin Neo-STX (0.38 pg toxin cell(-1)).The latter represented only 2.8% of the total toxins in this strain. High abundance of A. pacificum cysts correlated with enhanced percentages of water and organic matter in the sediment. In addition, sediment fractions of less than 63 mu m were examined as a favorable potential seedbed for initiation of future blooms and outbreaks of A. pacificum in the lagoon. A significant difference in the cyst distribution pattern was recorded among the lagoon's different zones, with the higher cyst abundance occurring in the inner waters. Also, no correlation due to the specific hydrodynamics of the lagoon was observed in the spatial distribution of A. pacificurn cysts and vegetative cells

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