Biallelic variants in SLC38A3 encoding a glutamine transporter cause epileptic encephalopathy

The solute carrier (SLC) superfamily encompasses >400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https://www.omim.org) are associated with rare Mendelian disorders including developmental and epileptic encephalopathy (DEE) and severe neurodevelopmental disorders (NDDs). Exome sequencing and family-based rare variant analyses on a cohort with NDD identified two siblings with DEE and a shared deleterious homozygous splicing variant in SLC38A3. The gene encodes SNAT3, a sodium-coupled neutral amino acid transporter and a principal transporter of the amino acids asparagine, histidine, and glutamine, the latter being the precursor for the neurotransmitters GABA and glutamate. Additional subjects with a similar DEE phenotype and biallelic predicted-damaging SLC38A3 variants were ascertained through GeneMatcher and collaborations with research and clinical molecular diagnostic laboratories. Untargeted metabolomic analysis was performed to identify novel metabolic biomarkers. Ten individuals from seven unrelated families from six different countries with deleterious biallelic variants in SLC38A3 were identified. Global developmental delay, intellectual disability, hypotonia, and absent speech were common features while microcephaly, epilepsy, and visual impairment were present in the majority. Epilepsy was drug-resistant in half. Metabolomic analysis revealed perturbations of glutamate, histidine, and nitrogen metabolism in plasma, urine, and cerebrospinal fluid of selected subjects, potentially representing biomarkers of disease. Our data support the contention that SLC38A3 is a novel disease gene for DEE and illuminate the likely pathophysiology of the disease as perturbations in glutamine homeostasis

Ketamine-Induced Oscillations in the Motor Circuit of the Rat Basal Ganglia

Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion

Effect of olive leaf extract rich in oleuropein on the quality of virgin olive oil

Effect of olive leaf extract rich in oleuropein on the quality of virgin olive oil was investigated. After extracting the dried and ground olive leaves with the assistance of homogenizer, the dried extract was partially dissolved into the oil to increase the oxidative stability of the oil. A face central composite design through response surface methodology was used to investigate the effects of enrichment conditions (extract content, time and mixing speed) on the responses, total phenolic content and oleuropein concentration of the enriched olive oil. Furthermore, antioxidant activity of the oil was determined by 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt method. Additionally, oxidative stability of the enriched oil was assessed by the Rancimat method. Total carotenoid content, peroxide value, alpha-tocopherol and chlorophyll were also measured, respectively. Addition of 0.15% natural antioxidant increased the stability of the oil (ae46%). The antioxidant capacity of the enriched oil was almost 2.5 times higher than that of the untreated oil. Furthermore, olive leaf extract improved the quality of the virgin olive oil with respect to tocopherol, carotenoid and chlorophyll contents and peroxide value, respectively. The leaf sampling was also performed both in the autumn and summer to evaluate the possible seasonal effects on phenolic profile in order to be careful for selecting the proper harvesting time to apply the extract into the oil