DISC1 regulates N-methyl-D-aspartate receptor dynamics:abnormalities induced by a Disc1 mutation modelling a translocation linked to major mental illness

Abstract The neuromodulatory gene DISC1 is disrupted by a t(1;11) translocation that is highly penetrant for schizophrenia and affective disorders, but how this translocation affects DISC1 function is incompletely understood. N-methyl-D-aspartate receptors (NMDAR) play a central role in synaptic plasticity and cognition, and are implicated in the pathophysiology of schizophrenia through genetic and functional studies. We show that the NMDAR subunit GluN2B complexes with DISC1-associated trafficking factor TRAK1, while DISC1 interacts with the GluN1 subunit and regulates dendritic NMDAR motility in cultured mouse neurons. Moreover, in the first mutant mouse that models DISC1 disruption by the translocation, the pool of NMDAR transport vesicles and surface/synaptic NMDAR expression are increased. Since NMDAR cell surface/synaptic expression is tightly regulated to ensure correct function, these changes in the mutant mouse are likely to affect NMDAR signalling and synaptic plasticity. Consistent with these observations, RNASeq analysis of the translocation carrier-derived human neurons indicates abnormalities of excitatory synapses and vesicle dynamics. RNASeq analysis of the human neurons also identifies many differentially expressed genes previously highlighted as putative schizophrenia and/or depression risk factors through large-scale genome-wide association and copy number variant studies, indicating that the translocation triggers common disease pathways that are shared with unrelated psychiatric patients. Altogether, our findings suggest that translocation-induced disease mechanisms are likely to be relevant to mental illness in general, and that such disease mechanisms include altered NMDAR dynamics and excitatory synapse function. This could contribute to the cognitive disorders displayed by translocation carriers

Biowaste-based biochar: A new strategy for fermentative bioethanol overproduction via whole-cell immobilization

This work explores the potential use of biochar as a microbial cell carrier enhancing the efficiency of alcoholic fermentations. Olive kernels, vineyard prunings, sewage sludge and seagrass residues were applied as biowaste for biochar production through pyrolysis at two different temperatures (250 °C and 500 °C), while a commercial type of non-biomass char was also employed for benchmarking purposes. Apart from vineyard prunings pyrolyzed at 250 °C, all other carbonaceous materials presented crystalline phases including halite, calcite, sylvite and/or silicon. Moreover, increase in pyrolysis temperature enhanced biochar's porosity and BET-specific surface area, which reached 41.7 m 2 g −1 for VP-based biochar remaining at lower levels (0.15–5.3 m 2 g −1 ) in other specimens tested. Elemental analysis demonstrated reduction in oxygen and increase in the carbon content of biochars produced at elevated temperatures, while biochar from seagrass included residues of chloride (0.3–5.14%). Three major yeasts were immobilized on materials exhibiting the highest surface areas and applied in repeated batch fermentations using Valencia orange peel hydrolyzates as feedstock. The biocatalysts developed using S. cerevisiae and K. marxianus immobilized on vineyard prunings-based biochar exhibited exceptional ethanol productivities as compared to the relevant literature, which reached 7.2 g L −1 h −1 and 7.3 g L −1 h −1 respectively. Although the aforementioned strains improved biofuel production by 36–52% compared to the conventional process, P. kudriavzevii KVMP10 was not efficient following immobilization on biochar. The approach constitutes an innovative method for bioenergy production, demonstrating a novel application of biochar in industrial biotechnology which incorporates important technological advances such as enhanced biofuel production and biomass recycling

Biowaste-based biochar: A new strategy for fermentative bioethanol overproduction via whole-cell immobilization

This work explores the potential use of biochar as a microbial cell carrier enhancing the efficiency of alcoholic fermentations. Olive kernels, vineyard prunings, sewage sludge and seagrass residues were applied as biowaste for biochar production through pyrolysis at two different temperatures (250 °C and 500 °C), while a commercial type of non-biomass char was also employed for benchmarking purposes. Apart from vineyard prunings pyrolyzed at 250 °C, all other carbonaceous materials presented crystalline phases including halite, calcite, sylvite and/or silicon. Moreover, increase in pyrolysis temperature enhanced biochar's porosity and BET-specific surface area, which reached 41.7 m 2 g −1 for VP-based biochar remaining at lower levels (0.15–5.3 m 2 g −1 ) in other specimens tested. Elemental analysis demonstrated reduction in oxygen and increase in the carbon content of biochars produced at elevated temperatures, while biochar from seagrass included residues of chloride (0.3–5.14%). Three major yeasts were immobilized on materials exhibiting the highest surface areas and applied in repeated batch fermentations using Valencia orange peel hydrolyzates as feedstock. The biocatalysts developed using S. cerevisiae and K. marxianus immobilized on vineyard prunings-based biochar exhibited exceptional ethanol productivities as compared to the relevant literature, which reached 7.2 g L −1 h −1 and 7.3 g L −1 h −1 respectively. Although the aforementioned strains improved biofuel production by 36–52% compared to the conventional process, P. kudriavzevii KVMP10 was not efficient following immobilization on biochar. The approach constitutes an innovative method for bioenergy production, demonstrating a novel application of biochar in industrial biotechnology which incorporates important technological advances such as enhanced biofuel production and biomass recycling